Download Lipids

Lipids
Simple Lipids:
 Triacylglycerols
 Di- &
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monoacylglycerols
Sterols & sterol
esters
Waxes
Tocopherols
Free (unesterified)
fatty acids
Cyanolipids
Complex Glycerolipids:
 Ether lipids
 Phosphatidic acid & related
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lipids
Phosphatidylglycerol
Diphosphatidylglycerol
(cardiolipin)
Phosphatidylinositol &
related lipids
Phosphatidylserine
Phosphatidylethanolamine
Complex Glycerolipids:
Phosphatidylcholine
•Mono- & digalactosyldiacylglycerols & related lipids from plants
•Glycosyldiacylglycerols & related lipids from animals
Sphingolipids:
oLong-chain or sphingoid bases
oCeramides
oSphingomyelin & related lipids
oSphingosine -1-phosphate
oMonoglycosylceramides (cerebrosides)
oOligoglycosylceramides (neutral)
oGangliosides
oSulfoglycosphingolipids
Fatty acids:
oSaturated straight-chain
oMonoenoic straight-chain
oMethylene-interrupted polyenoic
oConjugated & multimethylene-interrupted polyenoic
oBranched-chain
Some Miscellaneous Lipids:
oPhosphonolipids
oCarnitine & acylcarnitines
oCoenzyme A esters
oProteolipids
oAnandamide, oleamide & other fatty amides
Simple Lipids
S-1
Triacylglycerols(Triglyceride):
This includes all the vegetable oils,
such as those from corn (maize),
olive, palm, sunflower, and animal fats,
such as tallow, lard and butter,
as well as commercial products
such as margarines.
Most of these are depots fats where their main function may be
a store of energy, but some triacylglycerols (e.g. those of plasma
or liver) may have a more dynamic function.
S-2 Diacylglycerols
Diacylglycerols (or "diglycerides") are esters of the trihydric
alcohol glycerol in which two of the hydroxyl groups are
esterified with long-chain fatty acids.
S-3 Plant sterols and sterol derivatives
It is believed that sitosterol and 24-methylcholesterol are able to
regulate membrane fluidity and permeability in plant membranes in a
similar manner to cholesterol in mammalian cells. Also, plant sterols
can modulate the activity of membrane-bound enzymes.
Stigmasterol may be required specifically for cell proliferation.
Certain sterols in minute amounts, such as campesterol in
Arabidopsis thaliana, are precursors of oxidized steroids acting as
growth hormones collectively named brassinosteroids, which have
crucial importance for growth and development .
S-4 WAXES
a substance similar in composition and physical properties
to beeswax.
All of these tend to contain wax esters as major components,
i.e. esters of long-chain fatty alcohols with long-chain fatty acids.
Plant leaf surfaces are coated with a thin layer of waxy material
that serves a myriad of functions.
This layer is microcrystalline in structure and forms the outer boundary
of the cuticular membrane; it is the interface between the plant and
the atmosphere.
The major constituents of plant leaf waxes
Compound Structure
n-Alkanes
CH3(CH2)xCH3
Alkyl esters
CH3(CH2)xCOO(CH2)yCH3
Fatty acids
CH3(CH2)xCOOH
Fatty alcohols (primary)
CH3(CH2)yCH2OH
Fatty aldehydes
CH3(CH2)yCHO
Ketones
CH3(CH2)xCO(CH2)yCH3
Fatty alcohols (secondary)
CH3(CH2)xCHOH (CH2)yCH3
ß-Diketones
CH3(CH2)xCOCH2CO(CH2)yCH3
21 to 35C - odd numbered
34 to
62C - even numbered
16 to 32C – even numbered
22 to 32C - even numbered
22 to 32C - even numbered
23 to 33C - odd numbered
23 to 33C - odd numbered
27 to 33C - odd numbere
S-5 TOCOPHEROLS
S-6 TOCOPHEROLS
Tocopherols constitute a series of related benzopyranols (or
methyl tocols) that occur in vegetable oils.
In the tocopherols, the C16 side chain is saturated, and in the
tocotrienols it contains three double bonds.
The four main constituents are termed - alpha (5,7,8-trimethyl),
beta (5,8-dimethyl), gamma (7,8-dimethyl) and delta (8-methyl).
Of these, alpha-tocopherol is most readily absorbed from the
intestines.
They are all important natural antioxidants with some Vitamin E
activity, but only alpha-tocopherol (including synthetic material)
or natural mixtures containing this can be sold as 'Vitamin E'.
However, the tocotrienols are more potent antioxidants, while
gamma-tocopherol has some specific biological properties that
are distinct from those of alpha-tocophe
S-7 CYANOLIPIDS
Cyanolipids are components of the lipids of seeds
in the family Sapindaceae mainly, although some are known
from the Hippocastaneaceae and Boraginaceae.
Thus, type I and II cyanolipids are diesters of
1-cyano-2-hydroxymethylprop-2-en-1-ol and
1-cyano-2-hydroxymethylprop-1-en-3-ol, respectively,
while type III and IV cyanolipids are monoesters of
1-cyano-2-hydroxymethylprop-1-ene and
1-cyano-2-methylprop-2-en-1-ol, respectively.
Complex Lipid
C-1
ETHER LIPIDS
C-1-1 Alkyldiacylglycerols
Ether analogues of triacylglycerols, i.e. 1-alkyldiacyl-sn-glycerols,
are present at trace levels only if at all in most animal tissues,
but they can be major components of some marine lipids, especially.
C-1-2 Ether Phospholipids
C-2 PHOSPHATIDIC ACID AND RELATED LIPIDS
•Phosphatidic acid
•Lysophosphatidic acid
•Cyclic phosphatidic acid
•Pyrophosphatidic acid
•Lysobisphosphatidic acid
C-2-1 Phosphatidic Acid
Phosphatidic acid is not an abundant lipid constituent of any living
organism to common knowledge, but it is extremely important as an
intermediate in the biosynthesis of triacylglycerols and of most
phospholipids.
C-2-2 Lysophosphatidic Acid
Lysophosphatidic acid or 1-acyl-sn-glycerol-3-phosphate (LPA)
differs from phosphatidic acid in having only one mole of fatty acid
per mole of lipid.
Although it is present at very low levels only in animal tissues, it is
extremely important biologically, influencing many biochemical
processes.
These activities seem to be shared by the 1-alkyl- and alkenyl-ether
forms.
In particular, lysophosphatidic acid is an intercellular lipid mediator
with growth factor-like activities, and is rapidly produced and released
from activated platelets to influence target cells.
C-2-3 Cyclic phosphatidic Acid
Cyclic phosphatidic acid (sometimes termed ‘cyclic lysophosphatidic
acid’) was isolated originally from a slime mould, but has now been
detected in a wide range of organisms including humans.
It has a cyclic phosphate at the sn-2 and sn-3 positions of the glycerol
carbons, and this structure is absolutely necessary for its activities.
In particular, it is found in tissues subject to injury, and while it may have
some similar functions to lysophosphatidic acid per se, it also has some
quite distinct biological activities.
For example, cyclic phosphatidic acid is known to be a specific inhibitor
of DNA polymerase alpha.
C-2-4 Pyrophosphatidic Acid
Pyrophosphatidic acid or diacylglycerol pyrophosphate is an unusual
and little known phospholipid that was first identified in yeasts, and is
also know to be a product of a phosphatidic acid kinase reaction in
higher plants.
It is rapidly metabolized back to phosphatidic acid and thence to
diacylglycerols, and may have a function in the phospholipase C
and D signalling cascades in plants.
C-2-5 Lysobisphosphatidic acid
Lysobisphosphatidic acid or bis(monoacylglycerol)phosphate is an
interesting lipid from several standpoints (although it is only superficially
related to phosphatidic acid per se).
For example, its stereochemical configuration differs from that of other
animal glycero-phospholipids in that the phosphodiester moiety is linked
to positions sn-1 and sn-1' of glycerol, rather than to position sn-3, to
which the fatty acids are esterified.
The most abundant fatty acids can be 16:1, 18:1, 20:4 and especially
22:6(n-3), but this is very dependent on the specific tissue or cell type.
For example, the testis lipid contains more than 70% 22:5(n-6).
C-3 PHOSPHATIDYLGLYCEROL
Phosphatidylglycerol is a ubiquitous lipid that can be the main
component of some bacterial membranes, and it is found also in
membranes of plants and animals where it appears to perform
specific functions.
In plants, phosphatidylglycerol is found in all cellular membranes, but
it appears to be especially important in the thylakoid membrane
where it can comprise
10% of the total lipids
with a high proportion
(up to 70%) in the outer
monolayer.
In cereals such as oats,
a form with an additional
fatty acid linked to the
3'-hydroxyl of the
glycerol moiety has
been found.
C-4 DIPHOSPHATIDYLGLYCEROL (CARDIOLIPIN)
Diphosphatidylglycerol or 'cardiolipin' is a unique phospholipid with
in essence a dimeric structure, having four acyl groups and potentially
carrying two negative charges.
C- 5 PHOSPHATIDYLINOSITOL AND RELATED LIPIDS
C-5-1 Phosphatidylinositol
Phosphatidylinositol is an important lipid, both as a key
membrane constituent and as a participant in essential metabolic
processes in plants and animals (and in some bacteria). It is an
acidic (anionic) phospholipid that in essence consists of a
phosphatidic acid backbone, linked via the phosphate group to
inositol (hexahydroxycyclohexane).
C-5-2 Phosphatidylinositol phosphates
These are usually present at low levels only in tissues, typically
at about 1 to 3% of the concentration of phosphatidylinositol.
They are maintained at a steady state level in the inner leaflet of
the plasma membrane by a continuous and sequential series of
phosphorylation and dephosphorylation reactions by specific
kinases and phosphatases, respectively, which are regulated
and/or relocated through cell surface receptors for extracellular
ligands.
C-5-3 Phosphatidylinositol anchors for proteins
Phosphatidylinositol is known to be
the anchor that links a variety of
proteins to the external leaflet of the
plasma membrane via a glycosyl
bridge (glycosylphosphatidylinositol(GPI)-anchored proteins).
C-5-4 Lyso-phosphoinositides and
the glycerolphosphoinositides
It has long been known that the
water-soluble
glycerolphosphoinositides,
the fully deacylated forms of
phosphatidylinositol and the
phosphatidylinositol phosphates
have key roles in cellular signalling
pathways.
C-6 PHOSPHATIDYLSERINE
Phosphatidylserine or 1,2-diacyl-sn-glycero-3-phospho-L-serine is
the only amino acid-containing glycerophospholipid in animal cells.
Although it is distributed widely among animals, plants and
microorganisms, it is usually less than 10% of the total phospholipids,
the greatest concentration being in myelin from brain tissue. However,
it may comprise 10 to 20 mol% of the total phospholipid in the
plasma membrane and endoplasmic reticulum of the cell.
C-7 PHOSPHATIDYLETHANOLAMINE AND
RELATED LIPIDS
C-7-1 Phosphatidylethanolamine
Phosphatidylethanolamine (once given the trivial name 'cephalin') is
usually the second most abundant phospholipid in animal and plant
lipids and it is frequently the main lipid component of microbial
membranes.
As such, it is obviously a key building block of membrane bilayers.
The major pathway for biosynthesis of phosphatidylethanolamine
de novo in animals and plants is -
C-7-2 Lysophosphatidylethanolamine
Lysophosphatidylethanolamine, with one mole of fatty acid per
mole of lipid, is found in small amounts in tissues.
It is formed by hydrolysis of phosphatidylethanolamine by the
enzyme phospholipase A2, as part of a de-acylation/re-acylation
cycle that controls its overall molecular species composition.
C-7-3 N-Acyl phosphatidylethanolamine
N-acyl phosphatidylethanolamine in which the free amino group of
phosphatidylethanolamine is acylated by a further fatty acid is a
common constituent of cereal grains (e.g. wheat, barley and oats)
and of some other seeds, but it may occur in other plant tissues,
especially under conditions of physiological stress.
C-7-4 Mono- and dimethyl-phosphatidylethanolamine
Mono- and dimethyl-phosphatidylethanolamines are formed by
sequential methylation of phosphatidylethanolamine as part of a
minor mechanism for biosynthesis of phosphatidylcholine.
They are never found at greater than trace levels in animal or
plant tissues, and it is not known whether they have any more
specific functions.
On the other hand, they are more abundant in some bacteria,
especially those that interact with plants.
C-7-5 Phosphatidylethanol
Phosphatidylethanol has little in common with
phosphatidylethanolamine other than the obvious structural
similarity.
It is formed slowly in cell membranes, especially erythrocytes,
by a transphosphatidylation reaction from phosphatidylcholine in
the presence of ethanol, and catalysed by the enzyme
phospholipase D.
As such, it has been proposed as a biochemical marker for
alcohol abuse, since chronic alcoholics have very much higher
levels in the blood than healthy subjects who consume alcohol
in moderation.
C-8 PHOSPHATIDYLCHOLINE AND RELATED LIPIDS
C-8-1 PHOSPHATIDYLCHOLINE
Phosphatidylcholine (once given the trivial name 'lecithin')
is usually the most abundant phospholipid in animal and plants,
often amounting to almost 50% of the total, and as such
it is obviously the key building block of membrane bilayers.
C-8-2 Lysophosphatidylcholine
Lysophosphatidylcholine, with one mole of fatty acid per mole of
lipid in position sn-1, is found in small amounts in most tissues.
It is formed by hydrolysis of phosphatidylcholine by the enzyme
phospholipase A2, as part of the de-acylation/re-acylation cycle
that controls its overall molecular species composition.
C-8-3 Platelet-activating factor
Platelet-activating factor (PAF) or 1-alkyl-2-acetyl-sn-glycero-3phosphocholine is an ether analogue of phosphatidylcholine that
are biologically active.
C-8 MONO- AND DIGALACTOSYLDIACYLGLYCEROLS
AND RELATED LIPIDS FROM PLANTS
C-8-1 1. Mono- and digalactosyldiacylglycerols
Monogalactosyldiacylglycerols and digalactosyldiacylglycerols
are the main glycolipid components of the various membranes of
chloroplasts and related organelles, and indeed these are the most
abundant lipids in all photosynthetic tissues, including those of higher
plants, algae and certain bacteria.
In non-photosynthetic tissues of plants, the proportion of
glycosyldiacylglycerols is greatly reduced.
The predominant structures are 1,2-di-O-acyl-3-O-beta-Dgalactopyranosyl-sn-glycerol and 1,2-di-O-acyl-3-O-(6'-O-alpha-Dgalactopyranosyl-beta-D-galactopyranosyl)-sn-glycerol.
In higher plants, the galactolipids contain a high proportion of
polyunsaturated fatty acids, up to 95% of which can be linolenic acid
(18:3(n-3)).
It is clear that the galactosyldiacylglycerols have important functions
in photosynthesis, and the nature of these functions is the topic of
active research although much of the detail remains obscure.
C-8-2 Other neutral glycosyldiacylglycerols
1,2-Di-O-acyl-3-O-beta-D-glucopyranosyl-sn-glycerol has been
found in rice bran, where it occurs with the corresponding
galactolipids in an approximate ratio of 1:2. Interestingly, the two
forms differ appreciably in their fatty acid compositions.
C-8-3 Sulfoquinovosyldiacylglycerol
Sulfoquinovosyldiacylglycerol or 1,2-di-O-acyl-3-O-(6'-deoxy-6'sulfo-alpha-D-glucopyranosyl)-sn-glycerol (quinovose = 6deoxyglucose) is the single glycolipid most characteristic of
photosynthetic organisms.
It appears that this is the only lipid known to have a sulfonic acid
linkage.
Sphingolipids
Sph-1 LONG-CHAIN OR SPHINGOID BASES
Long-chain bases (sphingoids or sphingoid bases) are the
characteristic or defining structural unit of the sphingolipids (the root
term “sphingo-” was first coined by J.L.W. Thudichum in 1884
because the enigmatic nature of the molecules reminded him of the
riddle of the sphinx).
The bases are long-chain aliphatic amines, containing two or three
hydroxyl groups, and often a distinctive trans-double bond in position
4. To be more precise, they are 2-amino-1,3-dihydroxy-alkanes or
alkenes with (2S,3R)-erythro stereochemistry, with various further
structural modifications.
phytosphingosine or 4D-hydroxy-sphinganine ((2S,3R,4R)-2amino-octadecanetriol), although unsaturated analogues, for
example with a trans double bond in position 8, i.e.
dehydrophytosphingosine or 4D-hydroxy-8-sphingenine, tend to be
much more abundant.
Sphingoid bases are unusual amongst lipids in that they bear a small
positive charge at neutral pH, a consequence of intra-molecular hydrogen
bonding.
This enables them to cross membranes or move between membranes
with relative ease.
They inhibit protein kinase C indirectly, for example, by a mechanism
involving inhibition of diacylglycerol synthesis.
In addition, sphingoid bases are known to be potent inhibitors of cell
growth, although they stimulate cell proliferation and DNA synthesis.
They may have a protective role against cancer of the colon in humans.
Sph-2 CERAMIDES
Ceramides consist of a long-chain or
sphingoid base linked to a fatty acid via an amide bond.
They are rarely found at greater than trace levels in tissues, although
they can exert important biological effects.
Ceramides are formed as the key intermediates in the biosynthesis
of all the complex sphingolipids, in which the terminal primary
hydroxyl group is linked to carbohydrate, phosphate, etc.
Each organism and indeed each tissue may synthesise ceramides in
which there are a variety of di- and trihydroxy long-chain bases and
fatty acids, the latter consisting mainly of longer-chain saturated and
monoenoic (mainly (n-9)) chains (to C24 or greater), sometimes with
a hydroxyl group in position 2.
In plants, 2-hydroxy acids predominate sometimes accompanied by
small amounts 2,3-dihydroxy acids. However, ceramides are usually
converted rapidly to more complex sphingolipids, and the precursors
never accumulate.
Sph-3 SPHINGOMYELIN AND RELATED LIPIDS
Sphingomyelin (or ceramide phosphorylcholine) consists of a
ceramide unit with a phosphorylcholine moiety attached to position 1.
It is thus the sphingolipid analogue of phosphatidylcholine.
It is a ubiquitous component of animal cell membranes, where it is by
far the most abundant sphingolipid.
Indeed, it can comprise as much as 50% of the lipids in certain tissues,
though it is usually less abundant than phosphatidylcholine.
For example, it makes up about 10% of the lipids of brain. It is the
single most abundant lipid in erythrocytes of most ruminant animals,
where it replaces phosphatidylcholine entirely.
In this instance, there is known to be a highly active phospholipase A
that breaks down the glycerophospholipids, but not sphingomyelin.
Like phosphatidylcholine, sphingomyelin tends to be most abundant in
the plasma membrane, and especially in the outer leaflet, of cells.
Sphingomyelin does not appear to occur in plants or microorganisms,
and its evolutionary significance is a matter for speculation.
Sph-4 SPHINGOSINE-1-PHOSPHATE
Sphingosine-1-phosphate is an important cellular metabolite,
derived from ceramide that is synthesized de novo or as part of
the sphingomyelin cycle (in animal cells).
It has also been found in insects, yeasts and plants.
Like its precursors, sphingosine-1-phosphate is a potent
messenger molecule that perhaps uniquely operates both intraand inter-cellularly, but with very different functions from
ceramides and sphingosine.
The balance between these various sphingolipid metabolites
may be important for health.
For example, within the cell, sphingosine-1-phosphate promotes
cellular division (mitosis) as opposed to cell death (apoptosis),
which it inhibits in fact. Intracellularly, it also functions to regulate
calcium mobilization and cell growth in response to a variety of
extracellular stimuli.
Current opinion appears to suggest that the balance between
sphingosine-1-phosphate and ceramide and/or sphingosine
levels in cells is critical for their viability.
Sph-5 MONOGLYCOSYLCERAMIDES (CEREBROSIDES)
Galactosylceramide (Galß1-1'Cer) is the principal glycosphingolipid
in brain tissue, hence the trivial name "cerebroside", which was first
conferred on it in 1874, although it was much later before it was
properly characterized.
In fact, galactosylceramides are found in all nervous tissues, but
they can amount to 2% of the dry weight of gray matter and 12% of
white matter.
Presumably, it functions as part of the water permeability barrier. In
addition, higher than normal concentrations of glycosphingolipids
have been reported for the apical plasma membrane domain of
epithelial cells from intestine and urinary bladder.
However, of greater importance than the natural occurrence of
glucosylceramide per se is its role as the biosynthetic precursor of
lactosylceramide, and thence of the complex neutral
oligoglycolipids and gangliosides.
Glucosylceramide is usually the principal glycosphingolipid in plants,
especially in photosynthetic tissues, where the main long-chain
bases are C18 4,8-diunsaturated (Z/Z and E/Z) (not sphingosine as
illustrated).
Sph-6 LACTOSYLCERAMIDE AND
NEUTRAL OLIGOGLYCOSYLCERAMIDES
The most important and abundant of the diosylceramides is ß-Dgalactosyl-(1-4)-ß-D-glucosyl-(1-1')-ceramide, more conveniently
termed lactosylceramide (LacCer), using the trivial name of the
disaccharide.
Lactosylceramide may assist in stabilizing the plasma
membrane and activating receptor molecules in the special
micro-domains or rafts, as with the cerebrosides.
Neutral oligoglycosylceramides with from three to more than
twenty monosaccharide units in the chain have been detected in
animal tissues ('megaloglycolipids' with up to 50 carbohydrate
groups occur in erythrocytes).
Fucolipids are oligoglycolipids in any of the above series in
which a fucose (Fuc) residue substitutes for one of the usual
carbohydrate residues. In addition, certain of the oligoglycolipids
exist as lipid sulphates, and others are linked to sialic acid
residues, i.e. gangliosides.
Sph-7 GANGLIOSIDES
The name gangliosides was first applied by the German scientist
Ernst Klenk in 1942 to lipids newly isolated from ganglion cells of
brain.
They were shown to be oligoglycosylceramides containing Nacetylneuraminic acid (sialic acid or 'NANA' or 'SA' or Neu5Ac)
residues (or less commonly N-glycoloyl-neuraminic acid, Neu5Gc),
joined via glycosidic linkages to one or more of the monosaccharide
units, i.e. via the hydroxyl group on position 2, or to another sialic
acid residue.
In experimental systems, gangliosides have been shown to control
growth and differentiation of cells, and they have an important role in
the interactions between cells.
In particular, they have key functions in the immune defense systems,
and they are involved in pathological states such as cancer.
They act as receptors of interferon, epidermal growth factor, nerve
growth factor and insulin and in this way may regulate cell signaling.
Also, they bind specifically to various bacterial toxins, such as those
from botulinum, tetanus and cholera.
Sph-8 SULFOGLYCOSPHINGOLIPIDS
Sulfoglycosphingolipids (sometimes termed "sulfatides" or
"sulfatoglycosphingolipids") are glycosphingolipids carrying a
sulfate ester group attached to the carbohydrate moiety.
They were first identified in brain tissue by the pioneering lipid
chemist Thudichum in 1884, although it was much later before they
were properly characterized.
Although sulfoglycosphingolipids tend to be minor components of
tissues, 3'-sulfo-galactosylceramide or galactosylceramide-I3-sulfate
(illustrated) is one of the more abundant glycolipid constituents of
brain myelin, and it is also present in many other organs, especially
the kidney.
There are suggestions that they may have a similar role in kidney. A
high content of sulfatides in the gastric and duodenal mucosa,
where mucosa can be attacked by acid, pepsin and bile salts, may
be closely related to a function in mucosal protection.
Fatty acids
F-1 STRAIGHT-CHAIN SATURATED FATTY ACIDS
Straight- or normal-chain, saturated components (even-numbered)
make up 10-40% of the total fatty acids in most natural lipids.
The most abundant saturated fatty acids in animal and plant tissues
are straight-chain compounds with 14, 16 and 18 carbon atoms, but
all the possible odd- and even-numbered homologues with 2 to 36
carbon atoms have been found in nature in esterified form.
They are named systematically from the saturated hydrocarbon
with the same number of carbon atoms, the final 'e' being changed
to 'oic'
Acetic or ethanoic acid is of great importance in living tissues,
as the biosynthetic precursor of fatty acids and a range of other
metabolites.
 However, it is not often found in association with fatty acids of
higher molecular weight in esterified form in lipid molecules,
although it does occur esterified to glycerol in ruminant milk fats
(presumably in position sn-3).
 It is also the most common fatty acid linked to platelet-activating
factor.
 In seed oils, acetic acid occurs in position sn-3 of triacylglycerols of
Euonymus verrucosus, and in other vegetable oils, it has been
detected in linkage to the hydroxyl group of a hydroxy fatty acid,
which is in turn esterified to glycerol, i.e. as an estolide.
 Acetates of long-chain alcohols are found in plant and insect waxes
and as insect pheromones.
Propanoic acid is important as the biosynthetic precursor of
some amino acids.
 It is rarely found in esterified form in natural lipids, and to my
knowledge the only exception is for molecules related to plateletactivating factor.
Butanoic acid comprises 3-4% by weight (much more in molar terms)
of the total fatty acids in cow's milk, where it is found exclusively in
position 3 of the triacyl-sn-glycerols.
 It is found in milk fats of other ruminants, but not in the lipids of other
tissues of these species.
Hexanoic acid comprises 1-2% of the totals fatty acids in ruminant
milk triacylglycerols, where most of it is esterified to position 3 of the
triacyl-sn-glycerols.
 It is also found as a minor component of certain seed oils rich in
medium-chain saturated fatty acids (see below).
Medium-chain fatty acids, such as octanoic, decanoic and
dodecanoic, are found in esterified form in most milk fats, including
those of non-ruminants, though usually as minor components, but
not elsewhere in animal tissues in significant amounts.
 They are never detected in membrane lipids, for example. They are
absent from most vegetable fats, but with important exceptions.
 Thus, they are major components of such seed oils and coconut oil,
palm kernel oil and Cuphea species.
Myristic acid is a ubiquitous component of lipids in most living
organisms, but usually at levels of 1-2% only.
 However, it is more abundant in cow's milk fat, some fish oils and in those
seed oils enriched in medium-chain fatty acids (e.g. coconut and palm
kernel). This fatty acid is found very specifically in certain proteolipids,
where it is linked via an amide bond to an N-terminal glycine residue.
Palmitic acid is usually considered the most abundant saturated fatty
acid in nature, and it is found in appreciable amounts in the lipids of
animals, plants and lower organisms.
 It comprises 20-30% of the lipids in most animal tissues, and it is present in
amounts that vary from 10 to 40% in seed oils.
 Among commercial sources, it is most abundant in palm oil (40% or more).
Stearic acid is the second most abundant saturated fatty acid in nature,
and again it is found in the lipids of most living organisms.
 In lipids of some commercial importance, it occurs in the highest
concentrations in ruminant fats (milk fat and tallow) or in vegetable oils
such as cocoa butter, and of course in industrially hydrogenated fats.
 It can comprise 80% of the total fatty acids in gangliosides.
Eicosanoic acid can be detected at low levels in most lipids of
animals, and not infrequently in plants and microorganisms.
 They do occur in many plant waxes, which by some estimations are
the most abundant lipids on earth, and in some animal waxes such
as wool wax. Saturated fatty acids up to 26:0 are normal
constituents of animal sphingolipids
Biosynthesis of saturated fatty acids
The biosynthesis of saturated fatty acids requires a primer
molecule, usually acetic acid in the form of its Coenzyme A ester,
and a chain extender, malonyl-CoA.
The latter is formed from acetyl CoA by the activity of the enzyme
acetyl-CoA carboxylase in which biotin is the prosthetic group
(and thus can be inhibited by avidin).
In the first step of the reaction, carbon dioxide is linked to the
biotin moiety, and this is subsequently transferred to acetyl-CoA
to form malonyl-CoA.
As a first step, both the primer and extender substrates are attached to
acyl carrier protein (ACP), which has the same prosthetic group as
Coenzyme A.
A sequence of reactions follows in which the chain is extended and
butanoate is formed, as illustrated.
First, 3-oxobutanoate is formed by a reaction catalysed by ß-ketoacylACP synthetase, this is reduced to 3-hydroxy-butanoate by ß-ketoacylACP reductase, which is in turn dehydrated to trans-2-butenoate by ßhydroxyacyl-ACP hydratase before it is reduced to butanoate by
enoyl-ACP reductase.
The process then continues with the addition of a further six units of
malonyl-ACP by successive cycles of these reactions until palmitylACP is formed.
At this point, a thioesterase removes the fatty acyl product and
converts it to the CoA-ester, which can then enter into the various
biosynthetic pathways for the production of specific lipids.
Or, the palmityl-CoA can be further elongated by C2 units to form
longer-chain fatty acids by a Type III fatty acid synthetase.
Medium-chain fatty acids are produced by enzymes in which the
specificity of the thioesterase component differs from normal, i.e. the
chain-elongation cycle is terminated prematurely.
F-2 STRAIGHT-CHAIN MONOENOIC FATTY ACIDS
Straight- or normal-chain (even-numbered), monoenoic components,
i.e. with one double bond, make up a high proportion of the total fatty
acids in most natural lipids.
Normally the double bond is of the cis- or Z-configuration, although
some fatty acids with trans- or E-double bonds are known.
The most abundant monoenoic fatty acids in animal and plant tissues
are straight-chain compounds with 16 or 18 carbon atoms, but
analogous fatty acids with 10 to 36 carbon atoms have been found in
nature in esterified form.
They are named systematically from the saturated hydrocarbon with
the same number of carbon atoms, the final 'ane' being changed to
'enoic'. Thus, the fatty acid with 18 carbon atoms and the structural
formula is systematically named cis-9-octadecenoic acid, although it
is more usual to see the trivial name oleic acid in the literature.
F-3 METHYLENE-INTERRUPTED DOUBLE BONDS
The lipids of all higher organisms contain appreciable quantities of
polyunsaturated fatty acids ('PUFA') with
methylene-interrupted double bonds, i.e.
with two or more double bonds of the
cis-configuration separated by a single methylene group.
In higher plants, the number of double bonds in fatty acids only rarely
exceeds three, but in algae and animals there can be up to six.
Two principal families of polyunsaturated fatty acids occur in nature that
are derived biosynthetically from linoleic (9-cis,12-cis-octadecadienoic)
and alpha-linolenic (9-cis,12-cis,15-cis-octadecatrienoic) acids.
Linoleic acid is a ubiquitous component of plant lipids, and of
all the seed oils of commercial importance.
 For example, corn, sunflower and soybean oils usually contain over
50% of linoleate, and safflower oil contains up to 75%.
 Although all the linoleate in animal tissues must be acquired from
the diet, it is usually the most abundant di- or polyenoic fatty acid in
mammals (and in most lipid classes) typically at levels of 15 to 25%,
although it can amount to as much as 75% of the total fatty acids of
heart cardiolipin.
gamma-Linolenic acid ('GLA' or 6-cis,9-cis,12-cisoctadecatrienoic acid or 18:3(n-6)) is usually a minor component
of animal tissues in quantitative terms (< 1%), as it is rapidly
converted to higher metabolites.
 It is found in a few seed oils, and those of evening primrose, borage
and blackcurrant have some commercial importance.
 Evening primrose oil (달맞이꽃)contains about 10% GLA, and is
widely used both as a nutraceutical and a medical product.
8-cis,11-cis,14-cis-Eicosatrienoic acid (dihomo-gamma-linolenic acid
or 20:3(n-6)) is the immediate precursor of arachidonic acid, and of a
family of eicosanoids (PG1 prostaglandins).
 However, it does not accumulate to a significant extent in animal tissue
lipids, and is typically about 1-2% of the phospholipid fatty acids.
Arachidonic acid (5-cis,8-cis,11-cis,14-cis-eicosatetraenoic acid or
20:4(n-6) is the most important metabolite of linoleic acid in animal
tissues, both in quantitative and biological terms.
 It is often the most abundant polyunsaturated component of the
phospholipids, and can comprise as much as 40% of the fatty acids of
phosphatidylinositol.
 Several families of eicosanoids are derived from arachidonate, including
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prostaglandins (PG2 series), thromboxanes, leukotrienes, and lipoxins, with
phosphatidylinositol being the primary source.
In addition, 2-arachidonoylglycerol and anandamide (Narachidonoylethanolamine) have important biological properties, although
they are minor lipids in quantitative terms.
While arachidonate is found in all fish oils, polyunsaturated fatty acids of the
(n-3) families tend to be present in much larger amounts.
Arachidonic acid is frequently found as a constituent of mosses, liverworts
and ferns, but there appears to be only one definitive report of its
occurrence in a higher plant (Agathis robusta).
The fungus Mortierella alpina is a commercial source or arachidonate.
alpha-Linolenic acid (9-cis,12-cis,15-cis-octadecatrienoic acid or
18:3(n-3)) is a major component of the leaves and especially of the
photosynthetic apparatus of algae and higher plants, where most of it
is synthesised.
 It can amount to 65% of the total fatty acids of linseed oil, where its
relatively susceptibility to oxidation has practical commercial value in
paints and related products.
 In contrast, soybean and rapeseed oils have up to 7% of linolenate, and
this reduces the value of these oils for cooking purposes. alpha-Linolenic
acid is the biosynthetic precursor of jasmonates in plants, which appear to
have functions that parallel those of the eicosanoids in animals.
 In animal tissue lipids, alpha-linolenic acid tends to be a minor component
(<1%), the exception being grazing non-ruminants such as the horse or
goose, where it can amount to 10% of the adipose tissue lipids.
11,14,17-Eicosatrienoic acid (20:3(n-3)) can usually be detected in
the phospholipids of animal tissue but rarely at above 1% of the total.
Somewhat higher concentrations may be found in fish oils.
Stearidonic acid (6,9,12,15-octadecatetraenoic or 18:4(n-3)) is
occasionally found in plants as a minor component, and it occurs in
algae and fish oils.
3,6,9,12,15-Octadecapentaenoic acid or 18:5(n-3) is a significant
component of the lipids of dinoflagellates, and it can enter the
marine food chain from this source.
8,11,14,17-Eicosatetraenoic acid (20:4(n-3)) is found in most fish
oils and as a minor component of animal phospholipids.
 It is frequently encountered in algae and mosses, but rarely in higher
plants.
5,8,11,14,17-Eicosapentaenoic acid ('EPA' or 20:5(n-3)) is one of
the most important fatty acids of the (n-3) family.
 It occurs widely in algae and in fish oils, which are major commercial
sources, but there are few definitive reports of its occurrence in higher
plants.
 It is an important constituent of the phospholipids in animal tissues,
especially in brain, and it is the precursor of the PG3 series of
prostaglandins.
 There is currently great interest in the role of this acid in neurological
disorders such as schizophrenia.
7,10,13,16,19-Docosapentaenoic acid (22:5(n-3)) is an important
constituent of fish oils, and it is usually present in animal
phospholipids at a level of 2-5%.
4,7,10,13,16,19-Docosahexaenoic acid ('DHA' or 22:6(n-3))
is usually the end point of alpha-linolenic acid metabolism in
animal tissues.
 It is a major component of fish oils, especially from tuna eyeballs,
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and of animal phospholipids, those of brain synapses and retina
containing particularly high proportions.
While it is found in high concentrations in many species of algae,
especially those of marine origin, it is not present in higher plants.
DHA has recently been shown to be the precursor of docosanoids,
termed 'resolvins', which are analogous to the eicosanoids and
may have related biological activities.
The concentration of DHA in tissues has been correlated with a
number of human disease states, and it is essential to many
neurological functions.
As a phospholipid constituent, it has profound effects on
membrane properties, and together with cholesterol may act by
modulating the structure and function of membranes.
The linoleic acid, which is the
primary precursor molecule for
the (n-6) family of fatty acids,
must come from the diet.
Biosynthesis of
polyunsaturated fatty acids
requires a sequence of chain
elongation and desaturation
steps, as illustrated below,
and the various enzymes
require the acyl-Coenzyme A
esters as substrates not intact
lipids (unlike plants).
The liver is the main organ
involved in the process.
Again, the alpha-linoleic acid,
which is the primary precursor
molecule for the (n-3) family
of fatty acids in animal tissues,
must come from the diet.
The main pathway to the
formation of
docosahexaenoic acid
(22:6(n-3)) requires a
sequence of chain elongation
and desaturation steps
(Delta-5 and Delta-6
desaturases), as illustrated
below, with acyl-Coenzyme A
esters as substrates.
F-4 POLYUNSATURATED WITH OTHER THAN
METHYLENE-INTERRUPTED DOUBLE BONDS
Conjugated fatty acids from animal tissues
Fatty acids with conjugated diene systems are found in tissues of
ruminant animals, and thence in meat and dairy products, where it is
formed as an intermediate or by-product in the biohydrogenation of
linoleic acid by microorganisms in the rumen.
The main isomer, 9-cis,11-trans-octadecadienoic acid, amounts to
about 1% of milk fat, and it may be accompanied by a small
proportion of positional and geometrical isomers (6,8- to 12,14-18:2).
There is considerable interest in conjugated linoleic acid ('CLA') at
present because of reports that it has a number of beneficial medical
properties, especially anti-cancer effects. It is also claimed to have
anti-atherosclerosis effects, to help the immune system and to affect
energy metabolism, promoting protein deposition as opposed to fat
(see our web-pages on CLA).
Conjugated fatty acids from plants
trans-10,trans-12-Octadecadienoic acid comprises about
10% of the seed oil of Chilopsis linearis and appears to be the
only long-chain conjugated dienoic fatty acid from plant
sources, although trans-2,cis-4-decadienoic acid is present in
estolide linkage to an allenic hydroxy acid in Stillingia oil.
 Conjugated dienoic fatty acids in refined oils are mainly artefacts
of processing.
In contrast, fatty acids with conjugated triene systems have
been found in a large number of different plant species. Of
these, 9-cis,11-trans,13-trans-octadecatrienoic (alphaeleostearic) acid is the most widespread and best known.
Tung oil is the main commercial source.
Bis- and polymethylene-interrupted unsaturated fatty acids
from animal tissues
The primitive animals, the sponges (family - Spongillidae) and
some other marine invertebrates are known to contains a wide
range of distinctive fatty acids, the demospongic acids, with
bis-methylene-interrupted cis-double bonds, and ranging in
chain-length from C16 to C34.
These have a cis,cis-dienoic system, either with the double
bonds in positions 5 and 9, or derived from 5,9-16:2 by chainelongation.
The last is usually a relatively minor component of sponges, and
was first reported from the cellular slime mould Dictyostelium
discoideum.
Bis- and polymethylene-interrupted unsaturated fatty acids from plants
Delta-5-unsaturated polymethylene-interrupted fatty acids, with cis-double
bonds only, are found in appreciable amounts in seeds, leaves and other
tissues of the relatively primitive plants, the gynosperms (conifers).
Of these, the best known is probably 5-cis,9-cis,12-cis-octadecatrienoic
('pinolenic') acid, which is widespread in species of pines.
5-cis,13-cis-Docosadienoic acid (16% of the total fatty acids) occurs in
the seed oil of a plant from a quite different family Limnanthes alba
(meadowfoam).
Trace levels of dienoic fatty acids with cis-double bonds in positions 5 and
9 have been found in a few other plant species, while 9,15octadecadienoate occurs in mango pulp. In addition, an analogue of
pinolenic acid with a trans double bond in position 5 (5t,9c,12c-18:3) is
the main fatty acid constituent of the seed oil of Aquilegia vulgaris
(columbine).
A positional isomer of this, i.e. 3-trans,9-cis,12-cis-octadecatrienoate, is
a common constituent of seed oils from the Compositae, and the all-cis
isomer has also been described.
F-5 BRANCHED-CHAIN FATTY ACIDS
Branched-chain fatty acids are common constituents of the
lipids of bacteria and animals, although they are rarely found in
the integral lipids of higher plants.
Normally, the fatty acyl chain is saturated and the branch is a
methyl-group.
However, unsaturated branched-chain fatty acids are found in
marine animals, and branches other than methyl may be
present in microbial lipids.
The most common branched chain fatty acids are mono-methylbranched, but di- and poly-methyl-branched fatty acids are also
known.
Their main function may be to increase the fluidity of lipids as an
alternative to double bonds, which are more liable to oxidation.
Saturated iso- and anteiso-methyl-branched fatty acids
iso-Methyl branched fatty acids have the branch point on the
penultimate carbon (one from the end), while anteiso-methylbranched fatty acids have the branch point on the antepenultimate carbon atom (two from the end) as illustrated.
Fatty acids with structures of this type and with 10 to more than
30 carbons in the acyl chain are found in nature, but those
most often encountered have 14 to 18 carbons.
They are common constituents of bacteria but are rarely found
in other microorganisms.
In higher plants, 14-methylhexadecanoic occurs at a level of
0.5 to 1% in seed oils from the family Pinaceae, where it
appears to be a useful taxonomic marker.
iso-/anteiso-Methyl-branched fatty acids are major components
of plant surface waxes.
Saturated mid-chain methyl-branched fatty acids
10-R-Methyloctadecanoic acid or tuberculostearic acid is a major
component of the lipids of the tubercle bacillus and related
bacterial species.
Indeed its presence in bacterial cultures and sputum from
patients is used in the diagnosis of tuberculosis.
It is also found in Corynebacterium and many other species.
Biosynthesis of branched chain fatty acids of this type involves
methylation of oleic acid esterified as a component of a
phospholipid, with S-adenosylmethionine as the methyl donor.
The resulting 10-methyleneoctadecanoyl residue is reduced to
the 10-methyl compound with NADPH as the cofactor.
A related mechanism is in used for biosynthesis of cyclopropane
fatty acids in bacteria.
Di- and poly-methyl-branched fatty acids
A number of isoprenoid fatty acids occur naturally in animal tissues
that are derived from the metabolism of phytol (3,7,11,15tetramethylhexadec-trans-2-en-1-ol), the aliphatic alcohol moiety of
chlorophyll.
These range from 2,6-dimethylheptanoic to 5,9,13,17tetramethyloctadecanoic acids, but those encountered most often
are 3,7,11,15-tetramethylhexadecanoic (phytanic) and 2,6,10,14tetramethylpentadecanoic (pristanic) acids.
4,8,12-Trimethyltridecanoic acid is especially common in fish and
other marine organisms.
Phytanic acid is formed in animal tissues by oxidation of phytol to
phytenic acid (only encountered in tissues under artificial feeding
conditions), followed by reduction.
The shorter chain isoprenoid fatty acids are formed from this by
sequential alpha- and/or beta-oxidation reactions.
In natural phytanic acid, each of the methyl groups would be
expected to have the D-configuration, but in that prepared via
chemical hydrogenation of phytol, the 3-methyl group is racemic
(D,L).
Unsaturated methyl-branched fatty acids
Monounsaturated methyl branched-chain fatty acids have been
detected in bacteria and marine animals.
Often, usually the branch is in the iso/anteiso-positions, but it can
also be more central in the aliphatic chain.
For example, one of the first acids of this type to be described was
7-methyl-7-hexadecenoic acid from lipids of the ocean sunfish
(Mola mola), while 7-methyl-6- and 7-methyl-8-hexadecenoic
acids were later found in a sponges.
Similar fatty acids with iso-/anteiso-methyl groups found in related
marine organisms include 13-methyltetradec-4-enoic, 14methylhexadec-6-enoic, 14-methylpentadec-6-enoic and 17methyloctadec-8-enoic acids, and many others.
It is possible that the primary origin of these fatty acids is in
bacteria, since many comparable fatty acids have been found in
bacteria, for example in Bacillus cereus and Desulfovibrio
desulfuricans.
Unsaturated methyl-branched fatty acids
Monounsaturated methyl branched-chain fatty acids have been
detected in bacteria and marine animals.
Often, usually the branch is in the iso/anteiso-positions, but it can
also be more central in the aliphatic chain.
For example, one of the first acids of this type to be described
was 7-methyl-7-hexadecenoic acid from lipids of the ocean
sunfish (Mola mola), while 7-methyl-6- and 7-methyl-8hexadecenoic acids were later found in a sponges.
Similar fatty acids with iso-/anteiso-methyl groups found in
related marine organisms include 13-methyltetradec-4-enoic, 14methylhexadec-6-enoic, 14-methylpentadec-6-enoic and 17methyloctadec-8-enoic acids, and many others.
It is possible that the primary origin of these fatty acids is in
bacteria, since many comparable fatty acids have been found in
bacteria, for example in Bacillus cereus and Desulfovibrio
desulfuricans.
Mycolic acids
The mycolic acids, major components of the Mycobacteria and
related species, are beta-hydroxy-alpha-alkyl branched structures of
high molecular weight (88 carbons or more).
Depending on species, these can contain a variety of functional
groups, including double bonds of both the cis- and transconfiguration (but when the latter they also possess an adjacent
methyl branch) and cyclopropane rings, which can also be of the cisand trans-configuration.
In addition, they can contain, methoxy-, epoxy- and keto groups,
which are also adjacent to a methyl branch normally.
The mycolic acids are key structural components of the membranes
of mycobacteria, where they appear to confer distinctive properties,
including a low permeability to hydrophobic compounds, resistance to
dehydration, and the capacity to survive the hostile environment of
the macrophage.
The beta-hydroxy group is especially important in that it is believed to
modulate both the phase transition temperature and the molecular
packing within the membrane.
While there is evidence that mycolic acid-containing glycolipids have
some influence on the host immune system, they do not appear to be
important for the virulence of the pathogenic Mycobacteria.
Some Miscellaneous Lipids
PHOSPHONOLIPIDS
Phosphonolipids consist of aminoethylphosphonic acid
residues, i.e. with a phosphorus-carbon bond, attached to a lipid
backbone, which can be either a ceramide or diacylglycerol.
The first of the sphingolipids to be discovered was ceramide 2aminoethylphosphonate, which was found in sea anemones.
Subsequently, it was detected in a variety of molluscs, protozoa,
bacteria, and even
bovine brain tissue,
sometimes
accompanied by
an N-methylethanolamine
analogue.
CARNITINE AND ACYLCARNITINES
Carnitine (L-3-hydroxy-4-aminobutyrobetaine or L-3-hydroxy-4N-trimethylaminobutanoic acid), and its acyl esters
(acylcarnitines) are essential compounds for the metabolism of
fatty acids.
Carnitine can be synthesised de novo in animal cells, but it is
believed that most comes from the diet. Its main function is to
assist the transport and metabolism of fatty acids
into mitochondria, where they are oxidized for energy production.
In so doing, carnitine maintains a balance between free and
esterified coenzyme A, since an excess of acyl- CoA
intermediates is potentially toxic to cells.
In addition, carnitine is required to remove any surplus of acyl
groups from mitochondria.
Coenzyme A esters
Before a fatty acid can be metabolized in tissues, for example by
being esterified, oxidized or subjected to synthetic modification, it
must usually be activated by conversion to a Coenzyme A ester or
acyl-CoA, with the fatty acid group linked to the terminal thiol moiety.
The thiol ester is a highly energetic bond that permits a facile
transfer of the acyl group to receptor molecules. This is true for the
simplest fatty acid of all, acetic acid (i.e. as acetyl-CoA), as well as
for long-chain fatty acids.
Coenzyme A (CoASH) itself is a highly polar molecule, consisting of
adenosine 3',5'-diphosphate linked to 4-phosphopantethenic acid
(Vitamin B5) and thence to ß-mercaptoethylamine.
Not only is it intimately associated with most reactions of fatty acids,
but it is also a key molecule in the catabolism of carbohydrates via
the citric acid cycle in which acetyl-CoA is a major end-product.
It is interesting that the 4-phosphopantetheine moiety, linked via its
phosphate group to the hydroxyl group of serine, is the active
component in another important molecule in lipid metabolism, acyl
carrier protein.
This is a small protein (8.8 kDa), which is part of the mechanism of
fatty acid synthesis.
PROTEOLIPIDS
In 1951, proteins that were soluble in organic solvents such as
chloroform-methanol were found in rat brain myelin, although it was
another twenty years before it was shown that they contained
covalently bound fatty acids and so differed from the lipoproteins.
Such proteins are now known to be widespread in nature with a
variety of important functions.
The term proteolipid is
used to define
all proteins
containing covalently
bound lipid moieties,
including fatty acids,
isoprenoids, cholesterol
and
glycosylphosphatidylinositol.
In the N-myristoylated proteins, myristic acid (14:0) specifically,
which is a ubiquitous but usually minor component of cellular lipids,
is bound to the amino-terminal glycine residue (of a relatively
conserved sequence of the protein) via an amide linkage that is
relatively stable to hydrolysis.
In the palmitoylated proteins, palmitic acid (16:0) is linked to one
or more (up to four) internal cysteine (or occasionally threonine or
serine) residues via labile thioester bonds.
Prenylated proteins are formed by attachment of isoprenoid lipid
units, farnesyl (C15) or geranylgeranyl (C20), via cysteine thio-ether
bonds at or near the carboxyl terminus. Such proteins are ubiquitous
in mammalian cells, where they can amount to up to 2% of the total
proteins, and they are increasingly being found in plants.
Relatively recently, proteins linked covalently to cholesterol was
discovered that cholesterol can be found in covalent linkage to
specific proteins, known as the "hedgehog" signalling family. These
are formed post-translationally by attachment of cholesterol via an
ester bond to glycine in a highly conserved region of the protein.
ANANDAMIDE, OLEAMIDE AND OTHER FATTY AMIDES
Fatty amides are produced synthetically in industry in large amounts (>
300,000 tons per annum) for use as ingredients of detergents, lubricants,
inks and many other products. In nature, fatty acids are linked to the
complex sphingolipids via amide bonds. However, here we are
concerned only with those simple fatty amides that occur naturally and
have profound biological functions.
Long-chain N-acylethanolamines are ubiquitous trace constituents of
animal and human cells, tissues and body fluids, with important
pharmacological properties.
Anandamide or N-arachidonoylethanolamine has attracted special
interest, because of its marked biological activities.
 Like the pharmacologically active compounds in marijuana or cannabis (from
Cannabis sativa), it exerts its effects through binding to and activating
specific cannabinoid receptors, designated 'CB1' and 'CB2', both of which are
membrane-bound G-proteins.
 CB1 is found in the central nervous
system and in some other organs,
including the heart, uterus, testis and
small intestine, while the CB2 receptor
is found in the periphery of the spleen
and other cells associated with
immunochemical functions,
but not in brain.
cis-9,10-Octadecenamide or 'oleamide' is a primary fatty acid
amide. It was first isolated from the cerebrospinal fluid of sleepdeprived cats, and has been characterized and identified as the
signalling molecule responsible for causing sleep.
Very recently, N-arachidonoyldopamine has been detected as
an endogenous component of mammalian nervous tissue with
distinctive biological effects.
N-Acylglycine derivatives of short-chain fatty acids (C2 to C12)
have long been recognized as minor constituents of urine and
blood, and their compositions may have some relation to
metabolic disease.
However, more recently, it has become apparent hat Narachidonylglycine is present in bovine and rat brain as well as
other tissues at low levels, and that it suppresses inflammatory
pain.