LIPID MAPS

2023

March 2023

Lipid of the Month

With the possible exception of cholesterol, it’s not often for a lipid to be in the news, but octan-3-one managed this recently thanks to its apparent nematicidal role in the oyster mushroom.

Predictably headlines varied from the measured “The mushroom that is both delicacy and predator” to the somewhat less measured “Killer mushroom releases fungus ‘nerve gas’ to paralyse victims before ‘rapid death’”.

The oyster mushroom, Pleurotus ostreatus is a delicacy in some parts of the world, naturally living on decaying wood which is poor in nitrogen. It’s known to kill nematodes, and ingest them as a source of nitrogen. A recent paper in Sci Adv¹ has identified octan-3-one as the compound responsible for dispatching the nematodes. Released from fragile structures called toxocysts, octan-3-one causes paralysis and cell death in the nematode by disrupting cell membrane integrity.

Octan-3-one is not unique to P. ostreatus, it is a volatile, scented molecule used as a pheromone in insects and plants² and found in other fungi too. A question that remains to be answered though, is how the toxocyst stores a compound which disrupts nematode cell membranes, without causing damage to its own.

References

A carnivorous mushroom paralyzes and kills nematodes via a volatile ketone
Sci Adv
2023
DOI 10.1126/sciadv.ade4809
Freshly Distilled Oil of the Leaves of Rasmarinus Officianalis L Contained 3-Octanone
Z Naturforsch
1978
DOI 10.1515/znc-1978-1-226

February 2023

Lipid of the Month

Over 100 years ago, Krabbe and Copenhagen described a rare inherited neurological condition which would become known as globoid cell leukodystrophy, or Krabbe disease¹. It’s now known to be characterized by an accumulation of the lipid psychosine in the membranes of cells such as Schwann cells and oligodendrocytes in the nervous system. It leaves these cells unable to provide the myelination around nerve axons which is necessary for nerve function.

Psychosine accumulates due to a deficiency in an enzyme encoded by the GALC gene. The most common mutations in GALC cause a form of Krabbe disease which is usually fatal in infancy, though some mutations result in an adult-onset phenotype². GALC encodes galactocerebrosidase which ordinarily cleaves the galactose headgroup from galactoceramides (for example, from (GalCer d18:1/16:0) in their degradation pathway. In its absence, the acyl chain of the molecule can be removed by acid ceramidase, leaving galactosyl-sphingosine, or psychosine, behind.

Evidence suggests that build up of psychosine, essentially ‘lyso’ galactosylceramide, disrupts the properties of the membrane³ (ref) which may contribute to the disease phenotype.

While Krabbe disease was described in 1916, psychosine was described much earlier. It was mentioned by Thudichum in 1884 in his treatise on the chemical constitution of the brain. Presumably it was named after its isolation from brain extracts (psycho- referring to the mind). The link between psychosine and Krabbe disease was made fifty years ago in 1972⁴.

References

A New Familial, Infantile Form Of Diffuse Brain-Sclerosis
Brain
1916
DOI 10.1093/brain/39.1-2.74
A novel compound heterozygous mutation in GALC associated with adult-onset Krabbe disease: case report and literature review
Neurogenetics
2022
DOI 10.1007/s10048-021-00682-1
Psychosine, the cytotoxic sphingolipid that accumulates in globoid cell leukodystrophy, alters membrane architecture
J Lipid Res
2013
DOI 10.1194/jlr.M039610
Globoid cell leukodystrophy: Additional deficiency of psychosine galactosidase
Biochem Biophys Res Commun
1972
DOI 10.1016/0006-291X(72)90381-6

January 2023

Lipid of the Month

Over the festive season, it’s likely many of our readers might have enjoyed an alcoholic drink or two. In doing so, they will have formed phosphatidylethanol in their blood, especially in red blood cell membranes. It has been suggested that phosphatidylethanol is responsible for some of the effects of alcohol on the body¹.

Phosphatidylethanol is formed from phosphatidylcholine by the enzyme phospholipase D². This enzyme removes the choline headgroup, generally using water to attack the choline-phosphate bond to form phosphatidic acid. However, ethanol can substitute for water in the reaction, resulting in phosphatidylethanol instead. The most common form detected has palmitoyl and oleoyl acyl chains (PEth 16:0/18:1)³, consistent with the most prevalent acyl chains in phosphatidylcholine.

Phosphatidylethanol remains in the body much longer than ethanol itself, potentially for 2-3 weeks. It acts as a clinical and forensic marker for alcohol consumption, and its abuse⁴, for example in assessing alcohol consumption prior to liver transplants, or in drink-driving cases, or even post-mortem. It’s said to be a more reliable marker than asking people how much alcohol they drink as there are many reasons why people might underestimate.

Given how long phosphatidylethanol remains in your system, and depending how festive your festive season was, it may be clear of your body by the end of ‘Dry January’, if you take part in that.

References

A Molecular Target for an Alcohol Chain-Length Cutoff J Mol Biol 2019 https://doi.org/10.1016/j.jmb.2018.11.028
J Mol Biol
2019
DOI 10.1016/j.jmb.2018.11.028
Formation of phosphatidylethanol in rat brain by phospholipase D
Biochem Biophys Res Comm
1987
DOI 10.1016/0006-291X(87)91507-5
Identification of 48 homologues of phosphatidylethanol in blood by LC-ESI-MS/MS
Anal Bioanal Chem
2010
DOI 10.1007/s00216-010-3458-5
Alcohol Biomarkers in Clinical and Forensic Contexts
Dtsch Arztebl Int
2018
DOI 10.3238/arztebl.2018.0309

2022

December 2022

Lipid of the Month

Just before Christmas 1938, a strange fish was landed in the South African port of East London. It would turn out that the fish was well known to science, but only from 400 million year old fossils called coelacanths. Far from being extinct as previously thought, the coelacanth line was alive (though maybe not well). Today, there are two known living species of coelacanth, in the genus Latimera, named after Majorie Courtenay-Latimer, the woman who preserved and studied that first specimen.

In 1964, the components of coelacanth bile were analysed¹, identifying a novel compound, a 27-carbon pentahydroxy sterol, as the major component. This bile alcohol, principally found as a sulphate conjugate, was termed latimerol.

Latimerol is described as primitive, being chemically more similar to cholesterol (from which it is derived) than bile alcohols and acids of other organisms, for instance cholic acid in humans.

Bile, with its component acids and alcohols, assists in solubilising dietary fats, which would be plentiful in the carnivorous coelacanth diet. In addition, bile alcohols and salts are known to act as pheromones and semiochemicals in fish². Whether laterimol has such a role is unknown. As the coelacanth habitat is relatively remote, and it is a critically endangered species³, further study is challenging. Indeed, we may never know the full role of latimerol should the coelacanth go extinct.

References

Comparative studies of ‘bile salts’. 20. Bile salts of the coelacanth, Latimeria chalumnae Smith
Biochem J
1964
DOI 10.1042/bj0930034
Bile Salts as Semiochemicals in Fish
Chemical Senses
2014
DOI 10.1093/chemse/bju039
The IUCN Red List of Threatened Species
Latimeria chalumnae. The IUCN Red List of Threatened Species
2000
DOI 10.2305/IUCN.UK.2000.RLTS.T11375A3274618.en

November 2022

Lipid of the Month

Nematodes have the option of a ‘time out’ period in their life cycle, partially due to a lipid. If food is in short supply, the temperature is not optimal, or there are too many nematodes in a small area, a nematode larva can moult into a ‘Dauer’ form. In this form (German for duration or enduring) the nematode enters a kind of suspended animation until conditions improve.

The molecule which signals population density, named Daumone, was identified in 2005¹ as a heptanoic acid linked to an unusual sugar, ascarylose, via an omega-1 hydroxy group. Ascarylose is named after the Ascaridoidea nematode family.

Ascarosides with far longer acyl chains make up a protective layer around within nematode eggs shells². In fact, nematodes produce a variety of hormones which share a common ‘core’ of ascarylose linked to varying length fatty acids and possibly ‘decorated’ with other chemical groups. These form a whole modular toolkit of signalling molecules in the nematode³ and have their own subclass within the LIPID MAPS structure database termed ascarosides.

If only we humans could hibernate while food and heat are in short supply!

References

Chemical structure and biological activity of the Caenorhabditis elegans dauer-inducing pheromone.
Nature
2005
DOI 10.1038/nature03201
Structure of the Ascarosides from Ascaris suum
J Nat Prod
1996
DOI 10.1021/np960236+
Comparative metabolomics reveals biogenesis of ascarosides, a modular library of small-molecule signals in C. elegans
J Am Chem Soc
2012
DOI 10.1021/ja210202y

October 2022

Lipid of the Month

In the northern hemisphere, as the trees display their autumn colours, in a process of ‘de-greening’ there is an abundance of phytol, a 20-carbon prenol primary alcohol containing four methyl branches. Phytol is part of chlorophyll and is liberated as chlorophyll is degraded, cleaving the phytyl ‘tail’ from yields phytol and chlorophyllide1.

Chlorophyll is also broken down in the guts of ruminants by the gut microbiota, and the phytol is converted to phytanic acid. This molecule is absorbed by the animal into its tissues. Because the human gut lacks organisms which degrade chlorophyll, dairy and meat products are the main source of phytanic acid in the human diet, and not any green vegetables. Inability to metabolise phytanic acid causes problems for humans2.

The presence of a methyl on the third carbon prevents phytanic acid being degraded by beta-oxidation, as is the case for many fatty acids. It needs to be broken down by alpha-oxidation, and deficiencies in enzymes of this pathway lead to conditions such as Refsum disease, where phytanic acid builds up in the body. Treatment for Refsum disease is to remove pytanic acid from the diet, by avoiding meat and dairy products.

Ironically, the solution to problems caused by a molecule coming from chlorophyll is to eat more greens!

References

Degradation pathway(s) of chlorophyll: what has gene cloning revealed?
Trends Plant Sci
2000
DOI 10.1016/s1360-1385(00)01735-0
Phytanic acid: production from phytol, its breakdown and role in human disease
Cell. Mol. Life Sci.
2006
DOI 10.1007/s00018-005-5463-y

September 2022

Lipid of the Month

Glucosyl sphingosine was first detected in mammalian tissue nearly fifty years ago when it was observed in patients with Gaucher's disease¹, This condition is characterized by a deficiency in glucocerebrosidase, the enzyme which removes the glucose from glucosyl ceramide to form ceramide. As a result, glucosyl ceramide accumulates in certain tissues.

Glucosyl sphingosine is formed from glucosyl ceramide by removal of the acyl group. This is an unusual reaction which is not observed in healthy subjects. In the skin of patients suffering from atopic dermatitis (AD) however, glucosyl sphingosine is seen in high amounts due to increased levels of an enzyme which specifically removes the acyl chain from glucosyl ceramide².

Glucosyl sphingosine has been implicated as the source of irritation and itchiness in AD³ with recent papers suggesting a mechanism by which it activates various molecular receptors and ion channels in the skin which seem to interact with each other^4,5.Understanding this mechanism more fully could help in treating the symptoms of AD.

References

Isolation and characterization of glucosylsphingosine from Gaucher's spleen
J Lipid Res
1974
Abnormal Expression of the Novel Epidermal Enzyme, Glucosylceramide Deacylase, and the Accumulation of its Enzymatic Reaction Product, Glucosylsphingosine, in the Skin of Patients with Atopic Dermatitis
Lab Invest
2003
DOI 10.1097/01.lab.0000059931.66821.92
Glucosylsphingosine induces itch-scratch responses in mice
Biomol. Ther. (Seoul)
2010
DOI 10.4062/biomolther.2010.18.3.316
Glucosylsphingosine evokes pruritus via activation of 5-HT2A receptor and TRPV4 in sensory neurons
Br. J. Pharmacol.
2022
DOI 10.1111/bph.15733
Activation of serotonin receptor 2 by glucosylsphingosine can be enhanced by TRPA1 but not TRPV1: Implication of a novel glucosylsphingosine-mediated itch pathway
Biochim Biophys Acta Biomembr
2022
DOI 10.1016/j.bbamem.2022.184014

August 2022

Lipid of the Month

Just when you thought it was safe to go back in the… soil

The microbial world is one huge battle ground as various organisms compete with each other. In 1990 a novel antibiotic was discovered produced by the bacterium Streptoverticillium fervens which had anti-fungal activity¹.

This molecule, called FR-900848 initially, is unusual due to the multiple cyclopropyl groups along the acyl chain which is linked to a nucleoside via an amide bond. The three-membered cyclopropyls, looking like shark teeth, led to the colloquial name Jawsamycin.

Jawsamycin stops the growth of fungi, but has no activity against bacteria. It acts by inhibiting the fungal enzyme SPT14 that produces another lipid, glycosylphosphatidylinositol. Specifically, it adds a sugar N-acetyl glucosamine to the phosphatidylinositol². While jawsamycin stops the fungal enzyme,it has no effect on the equivalent human enzyme.

Though chemically, jawsamycin could be considered a fatty-amide, the biosynthetic pathway leading to the formation of jawsamycin utilities polyketide synthase³. Thus jawsamycin is considered a linear polyketide.

Recently the polyketide synthases involved in creating molecules such as jawsamycin have been repurposed to produce polycyclopropanated fatty acids⁴. These are energy dense molecules which the authors state have potential to replace fossil fuels. If such fuels catch on,lots of bacteria will need to be grown in culture to produce enough fuel molecules.

We’re gonna need a bigger.. fermenter!

References

A novael antifungal antibiotic FR-900848
J Antibiot
1990
DOI 10.7164/antibiotics.43.748
Jawsamycin exhibits in vivo antifungal properties by inhibiting Spt14/Gpi3-mediated biosynthesis of glycosylphosphatidylinositol
Nat Commun
2020
DOI 10.1038/s41467-020-17221-5
Biosynthesis of the structurally unique polycyclopropanated polyketide-nucleoside hybrid jawsamycin (FR-900848).
Angew Chem Int Ed Engl.
2014
DOI 10.1002/anie.201402623
Biosynthesis of polycyclopropanated high energy biofuels
Joule
2022
DOI 10.1016/j.joule.2022.05.011

July 2022

Lipid of the Month

Vitamin K is essential in forming the enzymes of the blood clotting cascade. It was discovered by accident by Henrik Dam, who was studying cholesterol metabolism in chicks. He was feeding the chicks a cholesterol-free diet by extracting cholesterol from their food with chloroform. The chicks however started haemorrhaging. It was known that they could synthesise cholesterol, and adding vitamins A or D to the diet made no difference, so an unknown substance must be at play. The chloroform had not only extracted cholesterol, but also this unknown substance, initially named Koagulationsvitamin, or vitamin K¹.

Dam was awarded the Nobel Prize in 1943 for its discovery, along with Edward Doisy who elucidated its structure². This was vitamin K1, produced in green plants and also called phylloquinone. Bacteria produce a related family of molecules termed vitamin K2 or menaquinone, in which the prenyl chain is unsaturated and can vary in length.

Vitamin K is essential for humans because enzymes in the blood clotting cascade contain modified glutamic acid amino acids. Vitamin K acts as a co-factor in forming this modification³ and so without vitamin K, these enzymes can’t function and the blood doesn’t clot.

In plants of course, vitamin K1 has nothing to do with blood clotting, or even amino acid modification. It acts instead to move electrons in the photosynthetic machinery⁴. At some point in evolution, animals have repurposed the molecule to do a completely different job.

References

The Antihæmorrhagic Vitamin of the Chick.: Occurrence And Chemical Nature
Nature
1935
DOI 10.1038/135652b0
On the Constitution of Vitamin K1
J Am Chem Soc
1939
DOI 10.1021/ja01876a510
Structural and functional insights into enzymes of the vitamin K cycle
J Thromb Haemost
2016
DOI 10.1111/jth.13217
Phylloquinone in photosystem I: are quinones the secondary electron acceptors in all types of photosynthetic reaction centers?
Trends Biochem Sci
1988
DOI 10.1016/0968-0004(88)90206-X

June 2022

Lipid of the Month

7-dehydrocholesterol is the final precursor to cholesterol in the Kandutsch-Russell biosynthesis pathway¹. It’s also the molecule on which sunlight acts to form vitamin D, and in insects, cholesterol is converted back to 7-dehydrocholesterol on the pathway to synthesise the developmental ecdysone hormones².

Too much 7-dehydrocholesterol is, however, not a good thing. People with mutations in the enzyme which converts it to cholesterol, 7-Dehydrocholesterol reductase, show elevated levels of 7-Dehydrocholesterol. They suffer from a condition called Smith–Lemli–Opitz syndrome. This can manifest in many different ways, including physical, cognitive and behavioural symptoms of varying severity.

Some of the behavioural issues which Smith–Lemli–Opitz syndrome can cause include self-harm³, curiously, a process also seen in brooding female octopuses, and possibly for the same reason. Mother octopuses brooding their eggs change their behaviour dramatically. They fast, decline physiologically and ultimately die, often repeatedly and deliberately injuring limbs during this time. A recent paper⁴ has shown that the optic gland of the California two-spot octopus is key to this behaviour, and removal of the gland, which produces 7-dehydrocholesterol during brooding, stops the self-harm and death of the creature.

For octopuses, as with humans, there is more to 7-dehydrocholesterol than meets the eye.

References

Preputial gland tumor sterols. 3. A metabolic pathway from lanosterol to cholesterol
J Biol Chem
1960
DOI 10.1016/S0021-9258(18)64608-3
Neverland is an evolutionarily conserved Rieske-domain protein that is essential for ecdysone synthesis and insect growth
Development
2006
DOI 10.1242/dev.02428
Behavioral phenotype of RSH/Smith-Lemli-Opitz syndrome
Ment Retard Dev Disabil Res Rev
2000
DOI 10.1002/1098-2779(2000)6:2<131::AID-MRDD7>3.0.CO;2-R
Steroid hormones of the octopus self-destruct system
Curr Biol
2022
DOI 10.1016/j.cub.2022.04.043

May 2022

Lipid of the Month

Your skin has a tough job protecting you from the world. One of the many abuses it suffers is exposure to ultraviolet wavelengths of sunlight. This generates, via singlet oxygen, hydroperoxysqualene from squalene, one of the most abundant lipids on the skin surface.

As any of the double bonds in squalene can be attacked by singlet oxygen, there are six potential forms of singly hydroperoxidated squalene produced¹ which have been shown to accumulate on the skin. Shown here is 2-hydroperoxy-squalene. The presence of hydroperoxysqualene triggers inflammatory reactions, maybe contributing to the body’s response to sunburn² and even to acne³.

Hydroperoxysqualene induces expression of genes linked to inflammation but its effect has been shown to be mitigated by gamma-tocotrienol, a form of vitamin E⁴.

So, if you’re going to be enjoying a lot of sunshine, it might be wise, along with other precautions, to top up your vitamin E.

References

Mass Spectrometric Discrimination of Squalene Monohydroperoxide Isomers
J Oleo Science
2017
DOI 10.5650/jos.ess16159
The possible role of squalene and its peroxide of the sebum in the occurrence of sunburn and protection from the damage caused by U.V. irradiation
J Toxicol Sci
1984
DOI 10.2131/jts.9.151
A possible role for squalene in the pathogenesis of acne. I. In vitro study of squalene oxidation
Br J Dermatol
1986
DOI 10.1111/j.1365-2133.1986.tb04060.x
Gamma-Tocotrienol Reduces Squalene Hydroperoxide-Induced Inflammatory Responses in HaCaT Keratinocytes
Lipids
2010
DOI 10.1007/s11745-010-3458-4

April 2022

Lipid of the Month

Some lipids appear so bizarre that one checks whether the paper describing them was published on April 1st! That was certainly the case with Protegenin A and its sibling protegenins¹. With up to four conjugated carbon-carbon triple bonds in an 18-carbon chain, at first glance one might think these fatty acids must be synthetic, They are however, completely natural and not April Fools!

Protegenins are fatty acids produced by a strain of Pseudomonas protegens as weapons in the continual competition between microbes. The presence of this bacterium in the soil is known to protect plants from fungal infection². Similar families of polyyne lipids have been discovered in other bacteria, for example the Caryoynencins from Pseudomonas (now Trinickia) caryophylli³.

The likely production of protegenins in this bacterium was inferred from the presence of a cluster of genes predicted to have functions in the biosynthesis of polyyne fatty acids. Purification and analysis of the compounds secreted into the growth medium confirmed the existence of the protegenin family of compounds and their chemical structures..

Knocking out a gene essential for protegenin production resulted in significantly more cucumber seedlings rotting when grown in the presence of the knock-out than when grown with the ‘wild type’. While the molecular mechanism of how protegenins act seems as yet unknown, this experiment indicated that they have anti-fungal activity.

As spring is here in the northern hemisphere, and seeds are being sown, there are all kinds of seemingly odd compounds silently aiding their growth.

References

Protegenins A-D, Bacterial Polyynes Involved in the Antioomycete and Biocontrol Activities of Pseudomonas protegens.
ACS Chem Biol
2021
DOI 10.1021/acschembio.1c00276
Pseudomonas protegens sp. nov., widespread plant-protecting bacteria producing the biocontrol compounds 2,4-diacetylphloroglucinol and pyoluteorin
Nat Rev Microbiol
2005
DOI 10.1016/j.syapm.2010.10.005
Caryoynencins, potent antibiotics from a plant pathogen Pseudomonas caryophylli
Tetrahedron Letts
1987
DOI 10.1016/S0040-4039(00)96437-2

March 2022

Lipid of the Month

Those with a classical education might conclude sapienic acid is somehow connected to wisdom. In fact that’s only partly true. It is named after Homo sapiens, ‘wise man’ (allegedly), in whom it is believed to be unique among animals¹. Sapienic acid forms a significant part of sebum- the oily substance secreted by sebaceous glands.

These glands express a delta-six desaturase enzyme which converts palmitic acid to sapienic acid. While delta-six desaturases are common, they usually add a double bond at this position in fatty acids which are already desaturated at the delta-9 position. The skin desaturase is identical to the form found elsewhere, suggesting unique conditions within the sebaceous gland favouring desaturation of palmitic acid, rather than palmitoleic acid.

Sapienic acid acts as an anti-microbial agent, forming part of the skin’s defenses against infection². Why sapienic acid is absent from other animals appears to remain a mystery.

While sapienic acid is unique to humans in the animal kingdom, it is not unique in life. It is the major fatty acid of certain plant seeds, such as Thunbergia alata³. In this species, is it formed by the same route as in humans, by desaturation of palmitic acid. Had sapienic acid been discovered here first, who knows what it might have been called; maybe alatic acid or thunbergic acid?

References

Identification of the Δ-6 Desaturase of Human Sebaceous Glands: Expression and Enzyme Activity
J Invest Dermatol
2003
DOI 10.1046/j.1523-1747.2003.12123.x
Thematic Review Series: Skin Lipids. Antimicrobial lipids at the skin surface
J Lipid Res
2008
DOI 10.1194/jlr.R700016-JLR200
Occurrence of Cis-6-hexadecenoic acid as the major component ofThunbergia alata seed oil
Lipids
1971
DOI 10.1007/BF02531295

February 2022

Lipid of the Month

Eat a deadly carrot, and you’ll know about it. Plants of the Thapsia genus, collectively termed ‘deadly carrots’, cause serious digestive problems and even death in any mammal unfortunate enough to ingest them. Simply touching some can cause skin irritation. The toxicity, and medicinal properties, of deadly carrots has been known since antiquity in the Mediterranean regions where they grow¹. The Romans used its emetic and purgative properties for slimming. Doubtless an unpleasant, and possibly lethal strategy.

Like many umbelliferous species, Thapsia plants contain compounds to deter animals from eating them. The main toxin isolated from Thapsia is a sesquiterpene called thapsigargin. It has a guaianolide skeleton, which is likely derived from farnesyl pyrophosphate, though the biosynthesis has yet to be elucidated². This core is adorned with several fatty acyl groups.

Thapsigargin is a specific inhibitor of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) pump, essential for regulating calcium homeostasis within cells. Because it traps the pump in one conformation, thapsigargin has been essential in solving crystal structures of this protein.

As SERCA is a target for chemotherapeutics, thapsigargin and its analogues are being investigated as potential anti-cancer drugs³ and it has even been suggested as a lead compound for anti-virals against coronavirus⁴. In both cases, its low abundance naturally, and difficulty of chemical synthesis remain a challenge.

Thapsic acid, a 16-carbon dicarboxylic fatty acid, is also said to be named after Thapsia, from which it was first isolated, but the original work describing that seems to be lost, at least to this author.

References

Sesquiterpenoids from Thapsia Species and Medicinal Chemistry of the Thapsigargins
Prog Chem Org Nat Prod

DOI 10.1007/978-3-7091-6529-4_2
Localization and in-Vivo Characterization of Thapsia garganica CYP76AE2 Indicates a Role in Thapsigargin Biosynthesis
Plant Physiol
2017
DOI 10.1104/pp.16.00055
Thapsigargin—From Traditional Medicine to Anticancer Drug
Int J Mol Sci
2021
DOI 10.3390/ijms22010004
Multi-level inhibition of coronavirus replication by chemical ER stress
Nat Commun
2021
DOI 10.1038/s41467-021-25551-1

January 2022

Lipid of the Month

When the Prince of Morocco In Shakespeare’s ‘The Merchant of Venice’ utters the often misquoted line “All that glisters is not gold” these are not his own words, but attributed to Death. January’s lipid of the Month, Staphyloxanthin is golden, but not gold, and the organism that produces it can cause death.

Staphylococcus aureus is a serious human pathogen, frequently fatal in the pre-antibiotic era, and becoming increasingly so again as antibiotic resistance rises. The bacterium is named because of its golden colour, caused at least in part by staphyloxanthin, a carotenoid pigment.

Staphyloxanthin is a glucosyl ester of 4,4'-diaponeurosporen-4-oic acid, the glucose in turn esterified with 12-methyl tetradecanoic acid (anteisopentadecanoic acid). Initially, the alpha anomer of glucose was proposed¹ but later work delineated the biosynthetic pathway and showed the more common beta form of glucose was present².

Staphyloxanthin doesn’t exist just to make S. aureus look pretty on an agar plate. It has an antioxidant role in the cell, which may contribute to its virulence³. Thus drugs which inhibit staphyloxanthin synthesis could act as antibiotics.

One of the early steps in formation of the carotenoid is the joining of two farnesyl diphosphate molecules, this is done by an enzyme very similar to one involved in the early steps of cholesterol biosynthesis in humans and cholesterol-lowering drugs which inhibit this enzyme have been shown to inhibit staphyloxanthin formation too². Very recently, a designed peptide antibiotic termed MSI-1⁴ has been shown to have the same effect.

So while antibiotic resistance remains a major threat to human health, and it remains true that all that glisters is not gold, there remains more than a glister of hope for novel antibiotics.

References

Pigments of Staphylococcus aureus, a series of triterpenoid carotenoids
J Bact
1981
DOI 10.1128/jb.147.3.900-913.1981
Structure and Biosynthesis of Staphyloxanthin from Staphylococcus aureus
J Biol Chem
2005
DOI 10.1074/jbc.M505070200
Staphyloxanthin plays a role in the fitness of Staphylococcus aureus and its ability to cope with oxidative stres
2020
Infect Immun.
DOI 10.1128/IAI.00204-06
MSI-1 combats drug-resistant S. aureus by affecting bacterial viability and inhibiting carotenoid pigment production
Micro Res
2021
DOI 10.1016/j.micres.2021.126909

2021

December 2021

Lipid of the Month

At this time of year, one might get a message from a friend or family member asking

“What do you want from Santa? LOL”

But santalol isn’t Father Christmas laughing out loud, but rather a terpene from the heartwood of the sandalwood tree; Santalum album. If you’re giving, or receiving, perfume this Christmas, santalol might well be in the gift, as it’s valued in the perfume industry.

In fact there are two related santalols, alpha and beta. Alpha-santalol makes up over half of the oil distilled from the wood, beta-santalol being the other major component. Sandalwood oil has been used medicinally and religiously for thousands of years, with various modern medicinal properties ascribed to alpha-santalol¹.

The structure of the tricyclic alpha-santalol was established in 1963², and a chemical synthesis achieved shortly after³. The tree makes santalol by a different route however, starting by cyclisation of farnesyl pyrophosphate, a precursor of many prenol lipids, including cholesterol. There then follows addition of a hydroxyl by cytochrome P450s⁴.

So much sandalwood oil is now used that Santalum album is considered vulnerable to extinction. Recently, santalol has been produced biosynthetically in commercial quantities by cloning santalol-producing genes into Rhodobacter sphaeroides, and even bakers’ yeast⁵ . However, no doubt due to human nature, ‘authentic’ santalol will continue to be more highly valued than the biosynthetic, but identical, form.

References

Medicinal properties of alpha-santalol, a naturally occurring constituent of sandalwood oil: review
Nat Prod Res
2019
DOI 10.1080/14786419.2017.1399387
The stereochemistry of α- and β-santalol
Tetrahedron Letts
1963
DOI 10.1016/S0040-4039(01)90982-7
Total synthesis of α-santalol
Tetrahedron Letts
1967
DOI 10.1016/S0040-4039(00)90958-4
Biosynthesis of Sandalwood Oil: Santalum album CYP76F cytochromes P450 produce santalols and bergamotol
PLoS One
2013
DOI 10.1371/journal.pone.0075053
Optimized biosynthesis of santalenes and santalols in Saccharomyces cerevisiae
Appl Microbiol Biotechnol
2021
DOI 10.1007/s00253-021-11661-9

November 2021

Lipid of the Month

Undoubtedly the hottest lipid of the moment is capsaicin- the molecule which imparts the hot sensation we experience when eating chilli peppers and which helped win David Julius this year’s Nobel Prize in Physiology or Medicine. The concentration, and efficacy of these compounds relate to the ‘hotness’ which is measured on the Scoville scale¹. Capsaicin acts by stimulating heat receptors and Julius’ team used if to identify which particular protein receptor in sensory neurons it triggered². The receptor turned out to be TrpV1, a transmembrane protein located in nerve endings. It is also responsible for detecting high temperature. Put your hand in hot water, or a chilli in your mouth and TrpV1 allows cations to flood into the nerve cell, initiating a signal your brain interprets as heat.

Capsaicin, a vanillylamide of 8-methyl-6-nonenoic acid, is very lipophilic, explaining why milk or yoghurt, containing fats, can ease the spiciness of a curry, but water will not. Its presence in peppers deters mammals from eating the fruit and destroying the seeds by chewing them. This strategy might appear to have failed for humans, but serendipitously, our love of chilli means we now cultivate the plants, actively ensuring its genes live on. The avian version of TrpV1 does not react to capsaicin, so birds can eat peppers without the hot taste. They do not digest the seeds but excrete them, with a lump of fertilizer, to grow a new plant.

While capsaicin causes a sometimes painful burning sensation, and may be responsible for some of the more well-known effects of spicy food³, it can actually be used in the treatment of pain as prolonged exposure desensitizes the receptor such that it can no longer transmit a signal⁴.

So next time you have a meal containing chillies, remember the capsaicin, a Nobel-esque lipid!

References

Note on Capsicums
J. Am. Pharm. Assoc.
1912
DOI 10.1002/jps.3080010520
The capsaicin receptor: a heat-activated ion channel in the pain pathway
Nature
1997
DOI 10.1038/39807
Capsaicin—the spicy ingredient of chili peppers: A review of the gastrointestinal effects and mechanisms
Trends in Food Science & Technology
2021
DOI 10.1016/j.tifs.2021.08.034
Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses
Molecules
2016
DOI 10.3390/molecules21070844

October 2021

Lipid of the Month

October’s Lipid of the Month is N-Retinylidene-N-retinylethanolamine or A2E. It forms rarely, but accumulates in the eye and is associated with age-related eye diseases such as macular degeneration. It’s chemical identity was determined in 1996¹ .

Light falling on receptors in the retina isomerises a double bond in retinal, converting it from cis to trans. This triggers the process of signalling to the brain that you have seen something. There follows a series of reactions to recycle the retinal back to the cis conformation to detect another photon.

Sometimes, the retinal escapes this cycle and reacts with the ethanolamine headgroup of PE lipids. More rarely, but associated with exposure to bright light, this species can react with a second retinal to form A2E. While A2E formation is rare, there is no enzymatic mechanism to degrade it. Over time, this orange-coloured and fluorescent molecule accumulates in retinal pigment epithelial cells.

Clearly, coloured molecules in the eye are going to affect vision, but A2E can also disrupt membrane integrity as it behaves like a detergent. In addition, any (or all) of the double bonds in the retinal can be modified by reactive oxygen species to form epoxides which have been shown to cause DNA damage².

References

Ocular Age Pigment “A2-E”: An Unprecedented Pyridinium Bisretinoid
J. Am. Chem. Soc.
1996
DOI 10.1021/ja953480g
A2E, a byproduct of the visual cycle
Vision Res.
2003
DOI 10.1016/S0042-6989(03)00475-9

September 2021

Lipid of the Month

The most abundant fatty acid in the hair of most mammals, including humans, is 18-methyl-eicosanoic acid (18-MEA). It makes up as much as half of all the fatty acids in hair and is found exclusively on the surface of the cuticle¹. It is covalently linked to the exterior surface of the hair protein via thioester bonds where it functions to maintain a waterproof barrier to the hair surface. It has also been ascribed roles in keeping hair untangled².

Why this particular fatty acid, unusual for its anteiso methyl branch, is found on the hair surface is unclear, but studies have shown that the methyl group affects the way fatty acids are packed on a surface³ . The branched part of 18-MEA is formed from the amino acid isoleucine. Patients with maple syrup urine disease are unable to metabolise isoleucine and consequently their hair lacks 18-MEA⁴.

The thioester bond linking 18-MEA to the hair is broken by alkaline conditions, often found in hair colourants and perms, which means the surface lipid layer is damaged by these treatments. There are hair products on the market which contain 18-MEA, but as the linkage is created enzymatically as the hair grows from its follicle, it is hard to see how these would replace 18-MEA to the natural state.

References

Integral lipids of mammalian hair
Comparative Biochemistry and Physiology Part B: Comparative Biochemistry
1989
DOI 10.1016/0305-0491(89)90264-2
18-MEA and hair appearance
Journal of Cosmetic Science
2010
DOI 10.1111/j.1468-2494.2010.00609_6.x
Self-assembly of long chain fatty acids: effect of a methyl branch
Phys. Chem. Chem. Phys.
2014
DOI 10.1039/C4CP00512K
Hairs from Patients with Maple Syrup Urine Disease Show a Structural Defect in the Fiber Cuticle
Journal of Investigative Dermatology
1996
DOI 10.1111/1523-1747.ep12343618

August 2021

Lipid of the Month

The old joke says that the one thing worse than finding a caterpillar in your apple, is finding half a caterpillar. Of course, finding no caterpillar is even better! One of the chemicals fruit farmers use to keep apples, and other fruit, caterpillar-free is codlemone, 8E,10E-dodecadien-1-ol.

The codling moth (Cydia pomonella) is a major pest of fruit trees, its larvae feed on apples, pears, and also walnuts, causing serious economic damage. Female codling moths emit codlemone as a pheromone to attract a mate, so a trap baited with codlemone lures males in as the Sirens of myth lured sailors to their deaths with song. Alternatively, releasing codlemone throughout an orchard means males cannot locate a female. In either case, mating is disrupted and no larvae are produced to eat the fruit.

Codlemone acts synergistically with other volatile chemicals, some released by the moths and others, such as pear ester (ethyl 2E,4Z-decadienoate), by fruit trees themselves. This enables males to better locate females sitting on a good source of larval food. Mixtures of such pheromones in commercial products lead to more efficient mating disruption and fewer ruined apples¹.

A recent paper² suggests that moths began to produce codlemone via the duplication of fatty acid desaturase genes, allowing different functionalities to evolve which introduce specific double bonds to a lipid. First, a desaturase forms a double bond at carbon nine of lauryl-CoA. There follows a further desaturation resulting in double bonds at carbons eight and ten, before a reductase releases codlemone from the CoA.

Disrupting the mating behaviour of the codling moth with pheromones means less non-specific insecticide needs to be used, but still fewer caterpillars, whole or fractional, in our fruit.

References

Codling Moth Management and Chemical Ecology
Ann. Rev. Entomol.
2008
DOI 10.1146/annurev.ento.53.103106.093323
Evolution of the codling moth pheromone via an ancient gene duplication
BMC Biol.
2021
DOI 10.1186/s12915-021-01001-8

July 2021

Lipid of the Month

On and in the human body, microbes out-number our own cells by about ten to one. Increasingly, we are coming to understand that these commensal bacteria are actively interacting with us, influencing our immune systems, and also our behaviour¹. One way in which they do this is via signalling molecules which mimic those of our own bodies. Bacteroides vulgatus is a bacterium which is found in the human intestinal tract and produces a lipid called commendamide², N-acyl-3-hydroxypalmitoyl-glycine. Commendamide is an abbreviation of ‘commensal mimicking endogenous amide’ and, as the name suggests, it likely mimics amide lipids, such as the endocannabinoids which interact with G-protein coupled receptors (GPCR) to modulate various aspects of physiology as diverse as mood, memory, hormone and and immune system regulation. Endocannabinoids bind to the same GPCRs which are stimulated by compounds in cannabis, the most abundant being tetrahydrocannabinol.

It's unlikely however that commendamide induces the same feeling of being chilled and hungry as THC, as it interacts with a different GPCR to that which the endocannabinoids bind. Commendamide interacts with GPCR132/G2A, which is involved in signalling in the immune system. So B. vulgatus might be using it’s lipid signaling molecule to modulate our immune response to it being around.

There may be multiple roles for commendamide, it has been shown to solubilise cholesterol, lyse red blood cells, and possibly play a role in quorum sensing³. Undoubtedly the relationship between humans and our bacteria is a complex one, with much still to be discovered.

References

Gut Microbiota as a Mediator of Host Neuro-Immune Interactions: Implications in Neuroinflammatory Disorders
Mod Trends Psychiatry
2021
DOI 10.1159/000510416
Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist
Proc Natl Acad Sci U S A.
2015
DOI 10.1073/pnas.1508737112
The Bacteroidales produce an N-acylated derivative of glycine with both cholesterol-solubilising and hemolytic activity
Sci Rep
2017
DOI 10.1038/s41598-017-13774-6

June 2021

Lipid of the Month

On a warm summer evening at Old Warden airfield, England, the faint smell of June’s Lipid of the Month lingers in the still air. It comes from the engines of several antique, but still air-worthy, aeroplanes.

In the early years of the 20th century, castor oil, pressed from seeds of the castor oil plant Ricinus communis, was found to be a good lubricant for rotary aircraft engines¹. Ricinolein is the main component, forming up to 90% of the oil. Ricinolein is a triglyceride of ricinoleic acid, a fatty acid chemically similar to oleic acid but with the addition of a hydroxyl group at the 12 position. It’s likely these hydroxyls, together with the homogeneity of castor oil, confer the properties that make it a much better lubricant than other vegetable oils.

Over time, hot ricinolein will polymerise and could ‘gum up’ an engine, but as rotary engines either burn or eject all of their oil, it is never in the engine long enough for gumming up to be an issue. So successful were the castor-containing lubricants developed and sold by the Wakefield Oil Company, it changed its name to an abbreviation of castor oil, and Castrol sells motor oils to this day.

Ricinolein has many more uses; it’s found in paints, cosmetics, inks and more widely in the chemical industry. It’s even suggested to be a renewable resource for other chemicals which can be derived from it².

Castor oil is also probably most notorious for its laxative properties. Ricinoleic acid mimics prostaglandin E2 to stimulate smooth muscle contraction in the gut³. It is widely said that the continuous ejection of castor oil from aircraft engines had a laxative effect on the First World War pilots sitting behind those engines, but solid evidence for this is surprisingly difficult to find.

References

A History of Aircraft Piston Engine Lubricants
West Coast International Meeting and Exposition
1981
DOI 10.4271/810849
Castor oil as a renewable resource for the chemical industry
Eur. J. Lipid Sci. Technol. 2010
2010
DOI 10.1002/ejlt.200900138
Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors
Proc Natl Acad Sci U S A.
2012
DOI 10.1073/pnas.1201627109

May 2021

Lipid of the Month

May’s Lipid of the Month is generated by one of the immune system’s many mechanisms used to protect the body from pathogens. 2-chlorohexadecanal is formed when the vinyl ether bond of plasmalogen lipids containing a 1Z-hexadecenyl chain (for example 1-(1Z-hexadecenyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine) is attacked by endogenous hypochlorous acid (HOCl)¹. The resulting 2-chloroaldehyde can subsequently oxidise to form a 2-chloro fatty acid.

HOCl is produced by neutrophils from hydrogen peroxide and chloride ions with the aid of the enzyme myeloperoxidase, located in the lysosome. This relatively strong oxidising agent will react with many compounds, essentially destroying anything within the lysosome. HOCl also dissociates to hypochlorite, the active constituent of bleach, but it should not be necessary to stress that attempting to augment the immune system by adding bleach is a very bad idea!!

2-chlorohexadecanal is not simply a lipid breakdown product but acts as a signalling molecule of infection itself. Its presence indicates a site of infection or inflammation and attracts other neutrophils to the site². It can also induce expression of cyclooxygenase-2³, the enzyme which forms prostaglandin H2, another part of the inflammation pathway.

References

Reactive chlorinating species produced by myeloperoxidase target the vinyl ether bond of plasmalogens: identification of 2-chlorohexadecanal
J. Biol. Chem
2001
DOI 10.1074/jbc.M101447200
Reactive Chlorinating Species Produced during Neutrophil Activation Target Tissue Plasmalogens
J. Biol. Chem
2002
DOI 10.1074/jbc.M109489200
2-Chlorohexadecanal and 2-chlorohexadecanoic acid induce COX-2 expression in human coronary artery endothelial cells
Lipids
2008
DOI 10.1007/s11745-008-3189-y

April 2021

Lipid of the Month

Avocados are undoubtedly a dangerous fruit, with around 50,000 avocado-related knife injuries reported over a 10-year period in the US alone¹. But that’s not the only way the avocado plant can harm you. It has been known for a long time that the leaves are toxic to animals, especially to lactating livestock. Necrosis of the mammary gland tissues has been observed in goats and mice and cardiac problems follow eating avocado leaves in a variety of species.

The compound responsible for these effects was identified in 1995 as 1-acetoxy-2R-hydroxy-12Z,15Z-heneicosadien-4-one², more conveniently termed ‘Persin’ (from the Latin name of the Avocado Persea americana). Persin is a 21-carbon, acetylated fatty alcohol, with two double bonds, a keto and a hydroxyl group along the acyl chain. When chemically synthesised, only the R-hydroxyl form was shown to replicate the toxic effects of avocado leaves.

Many toxins can form the basis of drugs and the effects of persin on mammary gland tissue has attracted attention as a potential therapeutic against breast cancer³, though the absence of literature on this subject in very recent years may suggest such research is no longer active.

Evidently, persin is absent in any significant amount from avocado fruit, otherwise they would be inedible, but next time you cut an avocado, don’t hold it in your hand!

References

Avocado-related knife injuries: Describing an epidemic of hand injury
Am J Emerg Med
2020
DOI 10.1016/j.ajem.2019.06.051
Isolation and identification of a compound from avocado (Persea americana) leaves which causes necrosis of the acinar epithelium of the lactating mammary gland and the myocardium
Nat Toxins
1995
DOI 10.1002/nt.2620030504
A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells
Mol Cancer Ther
2006
DOI 10.1158/1535-7163.MCT-06-0170

March 2021

Lipid of the Month

Last month, across the world, people watched the stunning video of NASA’s Perseverance rover as it was lowered to the surface of Mars via the hydrazine-powered rockets of its ‘Skycrane’. It’s main mission: to search for signs of ancient life on the Red Planet. Here on Earth, some of our many forms of life actually produce the rocket fuel hydrazine.

Anammox bacteria, found in the ocean, anaerobic bogs and lakes, and in waste-water treatment plants, oxidise ammonia and nitrate to nitrogen and water, via a hydrazine intermediate. They do so in a lipid-bound compartment called the anammoxosome, the membrane of which contains unique lipids found nowhere else in nature. These molecules, including March’s Lipid of the Month 8-[5]-ladderane-octanoic acid, were first identified in 2002¹ and contain linearly fused cyclobutane groups called ‘ladderanes’ in their fatty acyl chains.

Ladderane lipids form a very tightly-packed membrane which is much less permeable than ‘normal’ membranes, and probably serves to prevent the highly reactive and toxic hydrazine escaping the anammoxosome, as well as efficiently maintaining a proton gradient for the production of ATP.

Hydrazine powers cranes on Mars, but it is contained by ladders on Earth, showing that biology is incredibly resourceful and the diversity of lipids, seemingly endless. Whether Perseverance will find signs of ancient Martian life remains to be seen, but if it does, what sort of lipids might the Martians have contained?

References

Linearly concatenated cyclobutane lipids form a dense bacterial membrane
Nature
2002
DOI 10.1038/nature01128

February 2021

Lipid of the Month

Quite a lot of February’s Lipid of the Month is being injected into people’s arms at the moment. It’s found in both the Pfizer-BioNTech and Moderna vaccines for COVID-19. 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) is a component of the liposome in these vaccines, the vehicle which protects the mRNA encoding the viral spike protein and delivers it into cells for translation.

DSPC is a commonly occurring phospholipid in eukaryotic cell membranes, it has two saturated fatty acyl chains of 18 carbons each and a charged phosphocholine head group. It has been used to study model membranes and liposomes for over forty years, so its physical properties in membranes are very well characterised. Commercially, DSPC is readily available and relatively inexpensive.

In the liposome, DSPC is a structural component, forming a stable lipid bilayer¹ which prevents leakage of the nucleic acid cargo. But the liposome is a complex object, the lipids don’t simply form a ‘bubble’ enclosing the mRNA. The structure is much more lipid-filled; lipids within the liposome interact with each other and with the mRNA cargo in addition to forming the outer ‘shell’.²

While these COVID vaccines are novel in that they are the first examples of mRNA vaccines delivered via liposomes, it is not the first case of drug delivery via liposomes in the clinic, and not even the first example of RNA delivery in this way.³ So while these vaccines are a triumph of science, they build on work, including lipid research, that has taken place over decades.

References

Nanomaterial Delivery Systems for mRNA Vaccines
Vaccines
2021
DOI 10.3390/vaccines9010065
Structure of Lipid Nanoparticles Containing siRNA or mRNA by Dynamic Nuclear Polarization-Enhanced NMR Spectroscopy
J. Phys. Chem. B
2018
DOI 10.1021/acs.jpcb.7b10795
The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs.
Nat. Nanotechnol.
2019
DOI 10.1038/s41565-019-0591-y

January 2021

Lipid of the Month

In more northerly locations, January’s lipid of the month is in relatively short supply. 1α,25-dihydroxyvitamin D3, or calcitriol, is the active form of vitamin D, which binds to the vitamin D receptor to regulate transcription of potentially thousands of genes. While classically known to be involved in controlling calcium and phosphate levels in the body, it also plays a role in many other processes, including inflammation, infection, immunity, and some cancers¹.

Vitamin D is a secosteroid (the prefix seco- from the latin ‘to cut’ indicating one of the sterol rings is broken) formed from 7-dehydrocholesterol. It’s in short supply in winter because the body needs sunlight to make that cut. Ultraviolet light falling on the skin cleaves a bond (between carbons 9 and 10 in the B ring) to form pre-vitamin D3, which isomerises spontaneously to vitamin D3, also known as cholecalciferol.

Cholecalciferol is the form which is found in vitamin supplements, and in foods such as fatty fish and eggs but it is not yet active. It must first undergo two hydroxylation reactions, one at each end of the molecule. The first reaction takes place in the liver to make 25-hydroxyvitamin D3, or calcidiol. Later, in the kidneys and other tissues, calcidiol has another hydroxyl group added, at the opposite end of the molecule to produce calcitriol.

There has been a great deal of research published over the past year on the link between vitamin D and COVID-19. At the time of writing there were over 300 such articles indexed on PubMed. Whether any effect is specific to this virus, or indicative of general immune health, we may never know. Given the many genes influenced by vitamin D, it’s definitely a complicated question to answer.

References

Primary Vitamin D Target Genes of Human Monocytes
Front. Physiol.
2019
DOI 10.3389/fphys.2019.00194

2020

December 2020

Lipid of the Month

In A Christmas Carol, Charles Dickens describes Marley’s ghost as having “a dismal light about it, like a bad lobster in a dark cellar.” Written before electric lighting and refrigeration, luminescent lobsters might have been a more commonly observed phenomenon than they are today.

The dismal light of Dickens’ decaying decapod would have been triggered by an acyl homoserine lactone (AHL), December’s lipid of the month.

Several species of bacteria, including Vibrio harveyi, an opportunistic pathogen of shellfish, produce light. Given it’s ecological niche, there would likely be lots of V. harveyi on the surface of a rotting lobster, and it’s only when there are lots in one place that they make light. AHL is used to sense how many bacteria are around using a system known as quorum sensing. Different species make different AHLs, each with specific acyl groups. In the case of V. harveyi, 3-hydroxybutyryl homoserine lactone is it’s calling-card¹.

Each bacterium secretes AHL and is able to sense its concentration in the environment. If the bacterium is swimming about in the sea, the AHL quickly gets diluted and as the concentration is very low, no light is produced. As a single bacterium could not make enough light to be detected, doing so would be futile. However, if there are lots of bacteria in one place, the concentration of AHL is increased because they’re all secreting it, and it acts to switch on transcription of the genes needed to generate light. Many bacteria in one place make enough light for the blue-green glow to be visible.

While it may be hard to see the evolutionary advantage in making rotting lobsters glow, species related to V. harveyi form symbiotic relationships with squid and fish, and live in their light-emitting organs where producing light is critical for the symbiosis.

Quorum sensing, far from just prompting bacteria to make the ghostly glow Dickens spoke of, is also critical for other bacterial properties, including many which have practical implications for humans. For example, the pathogen Pseudomonas aeruginosa uses N-(3-oxododecanoyl)homoserine lactone to sense how many of its fellow bacteria are around, which contributes to its virulence^2>.

References

Biosynthesis and stereochemistry of the autoinducer controlling luminescence in Vibrio harveyi
J. Bacteriol.
1993
DOI 10.1128/jb.175.12.3856-3862.1993
The Pseudomonas aeruginosa Quorum-Sensing Molecule N-(3-Oxododecanoyl)Homoserine Lactone Contributes to Virulence and Induces Inflammation In Vivo
J. Bacteriol.
2002
DOI 10.1128/jb.184.4.1132-1139.2002

November 2020

Lipid of the Month

Turn the clock back 50 years, and phospholipids were considered solely structural components of cell membranes. However, in the 1970s a compound which caused platelet aggregation, blood clotting, and promoted inflammation was identified. It was named platelet-activating factor (PAF); and in 1979 shown to be a phospholipid ¹

PAF is a phospholipid in which the glycerol has an alkyl group, typically of 16 carbons (though this varies) attached via an ether linkage at the sn-1 position. The sn-2 position is occupied by an acetate group while sn-3 position carries the phosphocholine headgroup. It interacts with a specific G-coupled protein receptor to cause some, if not all, of its effects and is active at picomolar concentrations.

PAF can be synthesised in two ways, either the ‘remodelling pathway’ by which it is synthesised from membrane alkyl/acyl phospholipids via the enzyme phoshpolipase A2 which removes the acyl chain at the sn-2 position, forming a lyso-phosphocholine. The sn-2 position is then enzymatically esterified with an acetyl group to form PAF. The other route to its synthesis is the ‘de novo’ route in which the alkylglycerol part is first formed, then the phosophocholine head group is added. Finally the acetyl group is added via the same enzyme as in the remodelling pathway.

Not only is this lipid involved in inflammatory and allergic processes, but it has also been implicated in cancers, and neurodegenerative diseases such as Alzheimers’². Platelet activating factor does much more than activate platelets and there is doubtless much still to be learnt about this molecule.

References

Platelet-activating factor. Evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators)
J. Biol. Chem
1979
Forty Years Since the Structural Elucidation of Platelet-Activating Factor (PAF): Historical, Current, and Future Research Perspectives
Molecules
2019
DOI 10.3390/molecules24234414

October 2020

Lipid of the Month

It’s October already and here in the northern hemisphere it is what the poet Keats described as ‘the season of mists and mellow fruitfulness’, which, he said, conspires with the sun to ‘swell the gourd’. October’s lipid of the month is found in, and named after, the gourd (Cucurbitaceae) family of plants, including Halloween and Thanksgiving’s iconic gourd, the pumpkin.

Cucurbitacin B is a particularly widespread cucurbitacin, present in many different plant species. Like other cucurbitacins it is a triterpenoid, a huge family of molecules formed from squalene which also encompasses cholesterol and the steroid hormones. Cucurbitacins often occur modified by sugars. Cucurbitacin B glucoside (LMST01010408), where a glucose is linked at the 2-position (the hydroxyl group towards the bottom left of the image) is also called arvenin I as it was first discovered in Anagallis arvensis- not a gourd but a primrose¹.

Many cucurbitacins have a bitter taste, indeed arvenin I is described as ‘strongly bitter’, and are likely produced as a defense to try and prevent the plant (and the pumpkin) being eaten. Ironically, some of these taste properties appeal to humans, so the very things designed to protect, actually encourage us to eat them. Of course this is still beneficial for the plant, as human cultivation ensures success for a species.

Various pharmacological properties have been ascribed to Cucurbitacin B, including anti-inflammatory and anti-cancer properties against several different tumour types, such as those in the liver ². It has even been reported to protect memory in a mouse-model of Alzheimers’ disease³.

So while LIPID MAPS is in no way giving you medical advice, remember if you’re making a pumpkin pie, carving a pumpkin lantern, or maybe both, there’s more to a pumpkin than a wholesome meal and seasonal fun.

References

Isolation and structures of arvenins from Anagallis arvensis L. (Primulaceae). New cucurbitacin glucosides
Chem Pharm Bull (Tokyo)
1978
DOI 10.1248/cpb.26.3107
Cucurbitacin B induces apoptosis and S phase cell cycle arrest in BEL-7402 human hepatocellular carcinoma cells and is effective via oral administration
Cancer Letters
2010
DOI 10.1016/j.canlet.2010.01.029
Cucurbitacin B induces neurogenesis in PC12 cells and protects memory in APP/PS1 mice
Cell Mol Med
2019
DOI 10.1111/jcmm.14514

September 2020

Lipid of the Month

Absentmindedly crush a leaf while out on a country walk and you are likely to set up a whole cascade of reactions within the plant. One of them results in the formation of Arabidopside A¹, a member of the arabidopside family of plant oxylipins discovered in the model plant, Arabidopsis thaliana.

The major lipids in plant membranes, particularly membranes of the chloroplast, are galactolipids, a glycerol esterified by two acyl chains and with a galactose sugar as the polar group. The arabidopsides are galactolipids produced in response to plant wounding or infection². They are characterised by the presence of oxophytodienoic acid and/or dinor-oxophytodienoic acid as the acyl chains. Arabidopside A contains both of these species, the former at the sn1 position, and the latter at sn2. Phytodienoic acids are known plant hormones in their own right and precursors of the well known plant hormone jasmonic acid. They are chemically similar to the mammalian inflammatory signalling molecules, the prostaglandins.

Exactly how the arabidopsides function isn’t really known, it’s been suggested that they are reservoirs of phytodienoic acids which can be released when needed, but that doesn’t explain why their concentration increases when a plant is wounded. Just imagine how much arabidopside you might cause a plant to make when you mow the lawn!

References

Arabidopsides A and B, two new oxylipins from Arabidopsis thaliana
Tetrahedron Letters
1993
DOI 10.1016/S0040-4039(03)01148-1
Wounding Stimulates the Accumulation of Glycerolipids Containing Oxophytodienoic Acid and Dinor-Oxophytodienoic Acid in Arabidopsis Leaves
Plant Physiology
2006
DOI 10.1104/pp.106.082115

August 2020

Lipid of the Month

Coprostanol, August’s lipid of the month, is used as a biomarker indicating the presence of sewage in the environment. It is formed by gut bacteria which reduce dietary cholesterol to produce coprostanol, a highly water-insoluble molecule which, in anaerobic conditions, can be stable for thousands of years. This means that coprostanol is not only useful to monitor modern cases of sewage contamination, but can also be used as an indicator of the presence of sewage in archaeological sites. Its very poor water solubility means that any coprostanol in a sample is likely to have originated within the sample, rather than have been deposited from contaminated water flowing through the area over time.

Just as cholesterol is reduced to coprostanol, other dietary sterols are reduced to their respective stanols by gut bacteria. The plant-based diet of ruminant animals results in more faecal stigmastanol, produced from sitosterol. Stanol biomarker ratios therefore can be diagnostic of the species of the faeces^[1].

A recent study in Science Advances^[2] analysed stanol biomarkers in 12400 year old coprolites (fossilised excreta) found in an Oregon cave. DNA evidence had previously suggested these were human in origin, but a question of contamination with modern DNA remained. Because coprostanol is not able to seep over time into a sample through contaminated water, and contamination during analysis is extremely unlikely (unless you’re doing science really badly!), the ratio of coprostanol to other sterols in the sample confirmed them to be “unequivocally” human in origin. This research adds to the body of knowledge and the debate surrounding the first human settlement of the Americas.

References

The origin of faeces by means of biomarker detection
Environment International
2002
DOI 10.1016/s0160-4120(01)00124-6
Pre-Clovis occupation of the Americas identified by human fecal biomarkers in coprolites from Paisley Caves, Oregon
Science Advances
2020
DOI 10.1126/sciadv.aba6404

July 2020

Lipid of the Month

July’s lipid of the month, chaulmoogric acid, is an ingredient in the first effective leprosy treatment. Found in the seeds of the chaulmoogra tree (Hydnocarpus wightianus), it’s an unusual fatty acid containing a cyclopentenyl group which is thought to act as a biotin mimic, though its mode of action isn’t really known.

Chaulmoogra oil had been used for centuries as an ointment to treat leprosy, but the viscous, insoluble and noxious substance was unsuitable for internal treatment. Alice Ball, a pharmaceutical chemist at the University of Hawaii solved that by developing a method of solubilising the (presumed) active ingredients of chaulmoogra oil, chaulmoogric acid and the related hydnocarpic acid, in useful quantities. Ball’s method was essentially saponification to release the fatty acids from triglycerides and then esterification.

Born in July 1892, Ball died aged only 24, before her method could be published and before she could know how effective it was. The work was continued, with no reference to Ball, by Arthur Dean, the preparation of Chaulmoogra oil becoming known as ‘Dean derivatives’. A review by Harry T Hollmann in 1922^[1] attempted to set the record straight. Hollmann, a doctor at Kalhihi hospital in Hawaii where leprosy patients were sent, had invited Ball to look into producing a soluble chaulmoogra oil derivative. In the review he explains how Ball, the first woman, and first African American to receive a Masters degree from the College of Hawaii, developed the process of producing ethyl esters of chaulmoogra oil. Under the name ‘Dean derivatives’, these were credited with curing 78 patients at the Kalhihi hospital, who were discharged “no longer a menace to society”^[2]. Alice Ball’s preparation remained the treatment for leprosy until the advent of antibiotics in the 1940s.

You can read more about Alice Ball in Brianna Bibel’s excellent blog, ‘The Bumbling Biochemist’

References

The Fatty Acids Of Chaulmoogra Oil In The Treatment Of Leprosy And Other Diseases
Arch Derm Syphilol.
1922
DOI 10.1001/archderm.1922.02350260097010
Treatment Of Leprosy With The Dean Derivatives Of Chaulmoogra Oil
J.Am.Med.Assoc.
1920
DOI 10.1001/jama.1920.02620480021007

June 2020

Lipid of the Month

Fatty acid esters of hydroxyl fatty acids (FAHFAs, or estolides) are a fairly recent addition to the known mammalian lipidome. They were described in 2016 as a class of lipids with both anti-diabetic and anti-inflammatory effects ^[1]. Given the combinatorial possibilities of linking a fatty acid with a further hydroxylated fatty acid, where the hydroxyl could be anywhere along the chain, the FAHFA family has potential to be vast.

One example, the linoleic acid ester of 13-hydroxylinoleic acid (13-LAHLA)^[2] has been shown to have anti-inflammatory effects. It suppresses expression of genes involved in inflammation such as interleukins 6 and 1beta. It also suppresses expression of cyclooxygenase 2, an enzyme in the prostaglandin synthesis pathway and the target of the commonly used drug ibuprofen.

While it is known that some FAHFAs are ligands for G-protein coupled receptors, their precise mechanism of action, and indeed the full extent of the family, remains to be worked out. There is still much work to be done.

References

Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects
Cell
October 2014
DOI 10.1016/j.cell.2014.09.035
Linoleic acid esters of hydroxy linoleic acids are anti-inflammatory lipids found in plants and mammals
J.Biol.Chem
May 2019
DOI 10.1074/jbc.RA118.006956

May 2020

Lipid of the Month

Sterol lipids function as hormones across a wide range of species and can have a dramatic effect on the morphology of an individual. 20-Hydroxyecdysone is one such sterol hormone which controls skin-shedding and body pattern in arthropods such as crabs and insects. Its effects on an individual can be dramatic.

A recent paper ^[1] from Antonia Monteiro’s lab showed 20-Hydroxyecdysone to have a pivotal role in controlling the size of ‘eye spots’ on the wings of the African butterfly Bicyclus anynana. Adults which emerge from their pupae in the wet season have large eyespots on their wings but those which reach adulthood in the dry season, lack eye spots and are a more dull brown colour.

This difference is determined by the temperature experienced by the caterpillar over two specific days of its life, just before it pupates. While many species show a difference in levels of 20-Hydroxyecdysone depending on temperature, Monteiro showed that in B. anynana, cells in the centre of what would become the eyespot contained the 20-Hydroxyecdysone receptor, making them very sensitive to the hormone.

20-Hydroxyecdysone is not just made by arthropods. Some plants also produce this hormone, presumably as a defence mechanism, disrupting the development of insects grazing on them.

References

Origin of the mechanism of phenotypic plasticity in satyrid butterfly eyespots
eLife
February 2020
DOI 10.7554/eLife.49544

April 2020

Lipid of the Month

Humans are unable to synthesise linoleic acid, and so we must obtain it through the food we eat. Linoleic acid was discovered to be essential in the diet by Mildred and George Burr, working at the University of Minnesota in 1930^[1]. They showed that fats were not simply of calorific value but some, including linoleic acid, were absolutely required for health.

Linoleic acid is an 18-carbon fatty acid with two double bonds and present in large amounts in many vegetable oils. It’s one of those polyunsaturated fats which the adverts tell us are good for us.

It’s a precursor to arachidonic acid, which in turn is a precursor to a great many lipidic signalling molecules in the body. A study published in January 2019 looked at the effect of coronavirus infection on cellular lipids and showed that linoleic to arachidonic acid metabolism was “the most perturbed pathway” on infection of cells in their model system.^[2]

References

On the nature and role of the fatty acids essential in nutrition
J. Biol. Chem.
January 1930
Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication.
Viruses
2019, 11(1), 73
DOI 10.3390/v11010073

March 2020

Lipid of the Month

Ergosta-5,7,22E-trien-3β-ol (Ergosterol) is a sterol found in cell membranes of fungi and protozoa, but not animals. The common name, "ergosterol", of this lipid is derived from the group of fungi from which it was first isolated — "ergot" fungi, of genus Claviceps.

The role of ergosterol in fungi is similar to that of cholesterol in animal cells and ergosterol is essential to their survival. Ergosterol is synthesized from lanosterol and several anti-fungal drugs work by targeting erogsterol — either by binding to it, resulting in devastating cellular leakage, or preventing the synthesis of ergosterol from lanosterol.

References

February 2020

Lipid of the Month

9-oxo-11R,15S-dihydroxy-5Z,13E-prostadienoic acid(PGE2) is an oxytocic prostaglandin. PGE2's synthetic equivalent, the drug "dinoprostone", is commonly administered during childbirth — to induce labor by stimulating uterine contraction; to promote cervical ripening; and to control postpartum hemorrhage (PPH). PGE2 has also been shown to be involved in stem cell development via modulation of the Wnt pathway.

References

Nobiletin: efficient and large quantity isolation fromorange peel extract
Biomed. Chromatogr
20: 133 –138 (2006)
DOI 10.1002/bmc.540
Nobiletin restoring beta-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer's disease model rats.
Neurosci Lett.
2006 Jun 12,400(3):230-4. Epub 2006 Apr 3.
DOI 10.1016/j.neulet.2006.02.077
Nobiletin and Derivatives: Functional Compounds from Citrus Fruit Peel for Colon Cancer Chemoprevention
Cancers
2019, 11(6), 867
DOI 10.3390/cancers11060867
The citrus flavonoid nobiletin confers protection from metabolic dysregulation in high-fat-fed mice independent of AMPK
J. Lipid Res.
First Published on January 21, 2020
DOI 10.1194/jlr.RA119000542

January 2020

Lipid of the Month

4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid (DHA) - Fatty Acids and Conjugates [FA01]-> Unsaturated fatty acids [FA0306] - is a long-chain omega-3 polyunsaturated fatty acid [PUFA] commonly found in brain and retina^[1,2]. DHA is thought to play a critical role in brain developent, to be involved in multiple aspects of cardiovascular function^[3], and is implicated in multiple diseases and developmental disorders when deficient^[1,3].

While DHA levels can be measured using isotope tracers, recent research demonstrates that it can be measured by natural abundance carbon isotope ratio analysis, which is less costly and generally safer^[4].

References

Essential Fatty Acids: the Importance of n-3 Fatty Acids in the Retina and Brain
Nutrition Reviews
Volume 50, Issue 4, April 1992, Pages 21–29
DOI 10.1111/j.1753-4887.1992.tb01286.x
Essential role of docosahexaenoic acid towards development of a smarter brain
Neurochem Int
2015 Oct;89:51-62. Epub 2015 Aug 28
DOI 10.1016/j.neuint.2015.08.014
Omega-3 fatty acids EPA and DHA: health benefits throughout life
Adv Nutr
2012 Jan;3(1):1-7. Epub 2012 Jan 5
DOI 10.3945/an.111.000893
Turnover of brain DHA in mice is accurately determined by tracer-free natural abundance carbon isotope ratio analysis
Journal of Lipid Research
January 2020, 61, 116-126
DOI 10.1194/jlr.D119000518

Furan fatty acids – Beneficial or harmful to health?
Progress in Lipid Research.
Volume 68, 2017, Pages 119-137.
DOI 10.1016/j.plipres.2017.10.002
High Concentrations of Furan Fatty Acids in Organic Butter Samples from the German Market.
J. Agric. Food Chem.
2014, 62 (34), pp 8740–8744
DOI 10.1021/jf502975b
Detailed Study of Furan Fatty Acids in Total Lipids and the Cholesteryl Ester Fraction of Fish Liver.
Food Analytical Methods
Volume 9, Issue 2, 2016, pp 459–468
DOI 10.1007/s12161-015-0211-x
Synthesis and scavenging role of furan fatty acids
Proceedings of the National Academy of Sciences of the United States of America.
Volume 111, Issue 33, 2014, pp. 3450-57.
DOI 10.1073/pnas.1405520111 2018

2018

December 2018

Lipid of the Month

2-Arachidonoylglycerol also known as 2-AG is a monoacylglycerol neurotransmitter that binds to cannabinoid receptors located in the mammalian central nervous system (including the brain) and peripheral nervous system ¹. 2-AG and anandamide (LMFA08040001) are involved in regulating a variety of physiological and cognitive processes as part of the endocannabinoid system (ECS) which includes fertility, pregnancy, appetite, pain-sensation, mood (depression and memory) and in mediating the pharmacological effects of cannabis ^(1,2,3). In contrast, ECS is up-regulated in numerous pathophysiological states such as inflammatory, neurodegenerative, gastrointestinal, metabolic and cardiovascular diseases, pain, and cancer therefore enhancement of endogenous endocannabinoid tone by inhibition of endocannabinoid degradation represents a promising therapeutic approach for the treatment of many diseases ⁽⁴⁾.

References

Endocannabinoids, exercise, pain, and a path to health with aging
Molecular Aspects of Medicine.
Volume 64, December 2018, pp. 68-78.
DOI 10.1016/j.mam.2018.10.001
The endocannabinoid system in mental disorders: Evidence from human brain studies
Biochemical Pharmacology
Volume 157, 2018, pp. 97-107
DOI 10.1016/j.bcp.2018.07.009
Chronic pain and cannabinoids. Great expectations or a Christmas carol.
Biochemical Pharmacology,
Volume 157, 2018, pp.33-42.
DOI 10.1016/j.bcp.2018.07.033
Enhanced endocannabinoid tone as a potential target of pharmacotherapy
Life Sciences
Volume 204, 1 July 2018, pp. 20-45.
DOI 10.1016/j.lfs.2018.04.054

November 2018

Lipid of the Month γ-Tocopherol is one of the eight types of vitamin E and abundantly found in seeds (almond, pumpkin, walnuts, pecans, etc.) It has antioxidant properties due to its capability to trap nitrogen-based free radicals or reactive nitrogen oxide species (RNOS). However, when γ-tocopherol is metabolised to 2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman (γ-CEHC) it inhibits cyclooxygenase (COX-2) and prostaglandin E2 activity exhibiting also anti-inflammatory properties⁽¹⁾. Many serious degenerative conditions, including atherosclerosis, various types of cancer and Alzheimer's disease, appear to be promoted by chronic inflammation and COX-2 inhibitors show great potential in the prevention of these diseases.

References

N/A

October 2018

Lipid of the Month

Epigallocatechin 3,3',-di-O-gallate, also known as EGCG is a polyketide lipid that belongs to the main class of flavonoids known as catechins which can be mainly derived or extracted naturally from green and black tea⁽¹⁾. However, as a flavonoid, this compound can be found in many other food products such cocoa, onions, plums, pecan and hazelnuts but in trace amounts. The widespread consumption of green tea around the world has been promoted due to its positive health effects attributed to the antioxidant and anti-inflammatory properties of compounds such EGCG contained within⁽². However, other studies have highlighted that EGCG might protect from oxidative damages and could reduce cancer risk or other diseases caused by free radicals⁽³⁾.

References

Medicinal Plants: Their Use in Anticancer Treatment.
Int Journal of Pharmacological Science Research
Volume 6. Issue 10, 2005, pp. 4103–4112
DOI 10.13040/IJPSR.0975-8232.6(10).4103-12
Green tea polyphenol epigallocatechin-3-gallate differentially modulates oxidative stress in PC12 cell compartments
Toxicology and Applied Pharmacology.
Volume 15. Issue 207(3), pp. 212-20.
DOI 10.1016/j.taap.2005.01.004
Effect of increased tea consumption on oxidative DNA damage among smokers: a randomized controlled study
Journal of Nutrition
Volume 133. Issue 10, 2003, pp. 3303S–3309S
DOI 10.1093/jn/133.10.3303S

September 2018

Lipid of the Month

Oleic acid (Systematic Name:9Z-octadecenoic acid) is a monounaturated fatty acid whose name derives from the latin word 'oleum', which means oil. It is the most common fatty acid in nature, typically occurring in esterified form in glycerolipids and phospholipids. The biosynthesis of oleic acid involves the action of the enzyme stearoyl-CoA 9-desaturase acting on the saturated precursor stearoyl-CoA.

References

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August 2018

Lipid of the Month

Jasmonic acid (systematic name: (1R,2R)-3-oxo-2-(pent-2Z-enyl)-cyclopentaneacetic acid) is an truncated octadecanoid present in several plants including jasmine. Jasmonic acids are a class of plant hormones which are involved in development, abiotic stress responses and plant-microbes interactions in defence and symbiosis. Derivates such as methyl-jasmonate are volatile and participate in long range signalling between plants. Jasmonic acid is synthesized from alpha linolenic acid which is first oxygenated by Lipoxygenase (13-LOX) and subsequently modified by beta oxidation to yield a C12 cyclic product.

References

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July 2018

Lipid of the Month

Sphingomyelins, such as SM(d18:1/16:0) (systematic name: N-(hexadecanoyl)-sphing-4-enine-1-phosphocholine) are a class of sphingolipids composed of the long-chain sphingosine base attached to a fatty acid via an N-acyl linkage and a phosphocholine head group. In humans, sphingomyelins represent ~85% of all sphingolipids, and typically make up 10-20 mol % of plasma membrane lipids. They resemble phosphatidylcholines in their general properties and three-dimensional structure, and in having no net charge on their head groups.

References

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May 2018

Lipid of the Month Deoxycholic acid (systematic name:3alpha,12alpha-Dihydroxy-5beta-cholan-24-oic acid), a C24 bile acid, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria. The two primary bile acids secreted by the liver are cholic acid and chenodeoxycholic acid. Bacteria metabolize chenodeoxycholic acid into the secondary bile acid lithocholic acid, and they metabolize cholic acid into deoxycholic acid. Sodium deoxycholate, the sodium salt of deoxycholic acid, is often used as a biological detergent to lyse cells and solubilise cellular and membrane components.

References

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April 2018

Lipid of the Month

Anandamide (Systematic Name: N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine), also known as N-arachidonoylethanolamine or AEA, is a fatty acid neurotransmitter derived from the non-oxidative metabolism of arachidonic acid an essential w-6 polyunsaturated fatty acid. It is synthesized from N-arachidonoyl phosphatidylethanolamine (NAPE) by multiple pathways and is degraded primarily by the fatty acid amide hydrolase (FAAH) enzyme, which converts anandamide into ethanolamine and arachidonic acid.

References

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March 2018

Lipid of the Month

Palmitelaidic acid (systematic name: 9E-hexadecenoic acid) is a trans fatty acid (the trans isomer of palmitoleic acid). Trans fatty acids are known to cause changes in plasma lipids and lipoprotein phenotypes, but the mechanisms involved are unknown. The major dietary sources of trans fatty acids are partly hydrogenated vegetable oils, mainly elaidic acid (9E-octadecenoic acid). Additional sources are animal and dairy fats (palmitelaidic acid and trans-vaccenic acid (11E-octadecenoic acid)) and partly hydrogenated fish oils. Palmitelaidic acid has been reported as the predominant trans-16:1 isomer in cheeses made with goat and sheep milk.

References

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February 2018

Lipid of the Month

ELV-N34, (Systematic Name:(16Z,19Z,22R,23E,25E,27Z,29S,31Z)-22,29-dihydroxydotetratriaconta-16,19,23,25, 27,31-hexaenoic acid) represents a novel class of lipid mediators biosynthesized in human retinal pigment epithelial (RPE) cells that are oxygenated derivatives of very long-chain polyunsaturated fatty acids (VLC-PUFAs,n-3). These mediators have been named elovanoids (ELV) and are necessary for neuroprotective signaling for photoreceptor cell integrity. Photoreceptor cells express the elongase enzyme ELOVL4 which catalyzes the biosynthesis of elovanoids from 22:6 fatty acids derived from DHA or EPA.

References

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January 2018

Lipid of the Month

Coniferonic acid (Systematic name:5Z,9Z,12Z,15Z-octadecatetraenoic acid) is a C18 Delta(5)-unsaturated bis-methylene-interrupted fatty acid commonly found in pine seed oil. It is assumed to be synthesized from alpha-linolenic acid (ALA; 18:3Delta(9,12,15)) by Delta(5)-desaturation. A unicellular green microalga Chlamydomonas reinhardtii also accumulates this fatty acid in a betaine lipid.

References

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February 2017

Lipid of the Month Hyodeoxycholic acid (HDCA) or 3alpha,6alpha-Dihydroxy-5beta-cholan-24-oic acid is a C-24 secondary bile acid, one of the metabolic byproducts of intestinal bacteria. HDCA is present in mammalian species in different proportions and is the main acid constituent of hog bile. Hyodeoxycholic acid undergoes glucuronidation in human liver and kidneys via the enzyme UDP-glucuronosyltransferase.

References

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January 2017

Lipid of the Month

Myristic acid, or tetradecanoic acid, is a common saturated fatty acid named after the nutmeg Myristica fragrans. Myristic acid is also found in palm kernel oil, coconut oil, butter fat and is a minor component of many other animal fats. It is used to synthesize flavor and as an ingredient in soaps and cosmetics. Myristoylation is a co-translational or post-translational modification where a myristoyl group, derived from myristic acid, is covalently attached by an amide bond to the alpha-amino group of an N-terminal glycine residue. Myristoylation plays an essential role in membrane targeting, protein-protein interactions and functions widely in a variety of signal transduction pathways.

References

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August 2016

Lipid of the Month Chenodeoxycholic acid (3alpha,7alpha-dihydroxy-5ß-cholan-24-oic acid) is a C24 bile acid and one of the main bile acids produced by the liver. Chenodeoxycholic acid is synthesized in the liver from cholesterol and can be conjugated in the liver with taurine or glycine, forming taurochenodeoxycholic acid or glycochenodeoxycholic acid. Chenodeoxycholic acid is the most potent natural bile acid for stimulating the nuclear bile acid receptor, farnesoid X receptor. The transcription of many genes is activated by FXR.

References

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July 2016

Lipid of the Month

Ceramides, such as Cer(d18:1/16:0) (systematic name: N-(hexadecanoyl)-sphing-4-enine) are a class of sphingolipids composed of the long-chain base sphingosine attached to a fatty acid via an N-acyl linkage. Ceramides are found in high concentrations within the cell membrane of cells. De novo synthesis of ceramide occurs in the endoplasmic reticulum. Ceramide is subsequently transported to the Golgi apparatus by either vesicular trafficking or the ceramide transfer protein CERT. Once in the Golgi apparatus, ceramide can be further metabolized to other sphingolipids, such as sphingomyelin (a key component of cell membranes) and the complex glycosphingolipids.

References

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June 2016

Lipid of the Month

Cyanidin (2-(3,4-Dihydroxyphenyl) chromenylium-3,5,7-triol) is a polyketide metabolite belonging to the anthocyanidin subclass of flavonoids. It is a pigment found in many red berries including grapes, bilberry, blackberry and blueberry. Cyanidin, like other anthocyanidins, has putative antioxidant and radical-scavenging effects which may protect cells from oxidative damage and reduce risk of cardiovascular diseases and cancer.

References

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May 2016

Lipid of the Month

Oleanolic acid ((3beta-hydroxyolean-12-en-28-oic acid)) is a naturally occurring pentacyclic triterpenoid related to betulinic acid. It is widely distributed in food and plants where it exists as a free acid or as an aglycone of triterpenoid saponins. Oleanolic acid is relatively non-toxic, hepatoprotective, and exhibits antitumor and antiviral properties.

References

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April 2016

Lipid of the Month

Palmitic acid (LMFA01010001), or hexadecanoic acid, is the most common saturated fatty acid found in animals, plants and microorganisms. As its name indicates, it is a major component of the oil from palm trees (palm oil), but can also be found in meats, cheeses, butter, and dairy products. Palmitic acid is the first fatty acid produced during fatty acid synthesis and the precursor to longer chain fatty acids. Palmitic acid is used to produce soaps and cosmetics. These applications utilize sodium palmitate, which is commonly obtained by saponification of palm oil.

References

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February 2016

Lipid of the Month

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, sperm, testicles and retina. It can be synthesized from alpha-linolenic acid or obtained directly from maternal milk or fish oil. It's systematic name is 4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid. DHA is the most abundant omega-3 fatty acid in the brain and retina. DHA comprises 40% of the polyunsaturated fatty acids (PUFAs) in the brain and 60% of the PUFAs in the retina. Fifty percent of the weight of a neuron's plasma membrane is composed of DHA.

References

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January 2016

Lipid of the Month

Sphingosine-1-phosphate (S1P) is an signaling sphingolipid and is composed of a C18 sphingoid base with a phosphate group at the C1 position. Phosphorylation of sphingosine to S1P is catalyzed by sphingosine kinase, an enzyme ubiquitously found in the cytosol and endoplasmic reticulum of various types of cells. Although S1P is of importance in the entire human body, it is a major regulator of vascular and immune systems. In the vascular system, S1P regulates angiogenesis, vascular stability, and permeability. In the immune system, it is now recognized as a major regulator of trafficking of T- and B-cells.

References

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September 2015

Lipid of the Month Geranial, or 3,7-dimethyl-2E,6-octadienal is a monoterpenoid with the molecular formula C10H16O. The two compounds are double bond isomers. The 2E-isomer is also called citral A. The 2Z-isomer is known as neral or citral B. Geranial is present in the oils of several plants, including limes, lemons and oranges and has a strong lemon odor. It also has strong antimicrobial qualities and pheromonal effects in insects.

References

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August 2015

Lipid of the Month

Mayolene-16 or 11R-hexadecanoyloxyoctadeca-9Z,12Z,15Z-trienoic acid is a member of a class of fatty esters (mayolenes) found in the larvae of the European cabbage butterfly, Pieris rapae. They are composed of esters between straight-chain fatty acids and 11-hydroxy alpha-linolenic acid. The mayolenes have been shown to act as potent chemical deterrents to larval predators such as ants.

References

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July 2015

Lipid of the Month

Myristoleic acid, or 9Z-tetradecenoic acid, is an omega-5 fatty acid. It is biosynthesized from myristic acid by the enzyme delta-9 desaturase, but it is uncommon in nature. One of the major sources of this fatty acid is the seed oil from plants of the family Myristicaceae, comprising up to 30 per cent of the oil in some species.

References

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June 2015

Lipid of the Month

Prostaglandin D2 (or PGD2) is a prostaglandin that binds to the receptor PTGDR, as well as CRTH2. It is a major prostaglandin produced by mast cells and recruits Th2 cells, eosinophils, and basophils. In mammalian organs, large amounts of PGD2 are found only in the brain and in mast cells. It is critical to development of allergic diseases such as asthma. Cellular synthesis occurs through the arachidonic acid cascade with the final conversion from PGH2 performed by PGD2 synthase (PTGDS).

References

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May 2015

Lipid of the Month

Lauric acid, or dodecanoic acid, is a saturated fatty acid with a 12-carbon atom chain. Lauric acid, as a component of triglycerides, comprises about half of the fatty acid content in coconut oil, laurel oil, and palm kernel oil. It is also found in human breast milk (6.2% of total fat), cow's milk and goat's milk. Industrially, it is mainly used for the production of soaps and cosmetics.

References

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April 2015

Lipid of the Month Lithocholic acid, or 3alpha-hydroxy-5beta-cholan-24-oic acid is a monohydroxy secondary bile acid that acts as a detergent to solubilize fats for absorption. Bacterial action in the colon produces lithocholic acid from chenodeoxycholic acid by reduction of the C7 hydroxyl group in the B ring. Lithocholic acid can activate the vitamin D receptor without raising calcium levels as much as vitamin D itself.

References

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March 2015

Lipid of the Month

Aldosterone (LMST02030026) is a steroid hormone of the mineralocorticoid family synthesized from cholesterol in the adrenal gland. It plays a central role in the regulation of blood pressure, mainly by acting on the distal tubules and collecting ducts of the nephron, increasing reabsorption of ions and water. When dysregulated, aldosterone is pathogenic and contributes to the development and progression of cardiovascular and renal disease. Aldosterone is part of the renin-angiotensin system and tends to promote Na⁺ and water retention, and lower plasma K⁺ concentration.

References

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February 2015

Lipid of the Month

Jasmonic Acid (LMFA02020001), is a C12 fatty acid which is is biosynthesized from linolenic acid by the octadecanoid pathway. It is a plant growth regulator involved in the signaling mechanisms for a variety of conditions including plant defense, wound healing, tuberization, fruit ripening, and senescence Jasmonic acid is also converted to a variety of derivatives including esters such as methyl jasmonate and may also be conjugated to amino acids.

References

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January 2015

Lipid of the Month

Chenodeoxycholic Acid (LMST04010032), along with cholic acid, is one of two primary bile acids found in humans. Chenodeoxycholic Acid is synthesized in the liver from cholesterol. It is known to aid digestion and can be used to dissolve gallstones and in the treatment of cerebral cholesterosis.

References

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Lipid of the Month

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