Lipids are a broad group of organic compounds which include , , , fat-soluble vitamins (such as vitamins Vitamin A, Vitamin D, Vitamin E and Vitamin K), , , , and others. The functions of lipids include storing energy, lipid signaling, and acting as structural components of .
Lipids are broadly defined as Hydrophobe or Amphiphile small molecules; the amphiphilic nature of some lipids allows them to form structures such as vesicles, multilamellar/unilamellar liposomes, or membranes in an aqueous environment. Biological lipids originate entirely or in part from two distinct types of biochemical subunits or "building-blocks": ketoacyl and isoprene groups.
Although the term lipid is sometimes used as a synonym for fats, fats are a subgroup of lipids called . Lipids also encompass molecules such as and their derivatives (including tri-, di-, monoglycerides, and phospholipids), as well as other sterol-containing such as cholesterol.
History
In 1815,
Henri Braconnot classified lipids (
graisses) in two categories,
suifs (solid greases or tallow) and
huiles (fluid oils).
In 1823, Michel Eugène Chevreul developed a more detailed classification, including oils, greases, tallow, waxes, resins, balsams and volatile oils (or essential oils).
The first synthetic triglyceride was reported by Théophile-Jules Pelouze in 1844, when he produced tributyrin by treating butyric acid with glycerin in the presence of concentrated sulfuric acid.[ Comptes rendus hebdomadaires des séances de l'Académie des Sciences, Paris, 1853, 36, 27; Annales de Chimie et de Physique 1854, 41, 216]
In 1827, William Prout recognized fat ("oily" alimentary matters), along with protein ("albuminous") and carbohydrate ("saccharine"), as an important nutrient for humans and animals.
For a century, chemists regarded "fats" as only simple lipids made of fatty acids and glycerol (glycerides), but new forms were described later. Theodore Gobley (1847) discovered phospholipids in mammalian brain and hen egg, called by him as "". Thudichum discovered in human brain some phospholipids (cephalin), glycolipids (cerebroside) and sphingolipids (sphingomyelin).
The terms lipoid, lipin, lipide and lipid have been used with varied meanings from author to author.
The word lipide, which stems etymologically from Greek λίπος, lipos 'fat', was introduced in 1923 by the French pharmacologist Gabriel Bertrand.
In 1947, T. P. Hilditch defined "simple lipids" as greases and waxes (true waxes, sterols, alcohols).
Categories
Lipids have been classified into eight categories by the
LIPID MAPS consortium
as follows:
Fatty acyls
Fatty acyls, a generic term for describing fatty acids, their conjugates and derivatives, are a diverse group of molecules synthesized by chain-elongation of an
acetyl-CoA primer with
malonyl-CoA or methylmalonyl-CoA groups in a process called fatty acid synthesis.
They are made of a hydrocarbon chain that terminates with a
carboxylic acid group; this arrangement confers the molecule with a polar,
hydrophilic end, and a nonpolar,
hydrophobic end that is
insoluble in water. The fatty acid structure is one of the most fundamental categories of biological lipids and is commonly used as a building-block of more structurally complex lipids. The carbon chain, typically between four and 24 carbons long,
may be saturated or unsaturated, and may be attached to
containing
oxygen,
,
nitrogen, and
sulfur. If a fatty acid contains a double bond, there is the possibility of either a
cis or
trans geometric isomerism, which significantly affects the molecule's configuration.
Cis-double bonds cause the fatty acid chain to bend, an effect that is compounded with more double bonds in the chain. Three double bonds in 18-carbon
linolenic acid, the most abundant fatty-acyl chains of plant
thylakoid membranes, render these membranes highly
fluid despite environmental low-temperatures,
and also makes linolenic acid give dominating sharp peaks in high resolution 13-C NMR spectra of chloroplasts. This in turn plays an important role in the structure and function of cell membranes.
Most naturally occurring fatty acids are of the
cis configuration, although the
trans form does exist in some natural and partially hydrogenated fats and oils.
Examples of biologically important fatty acids include the , derived primarily from arachidonic acid and eicosapentaenoic acid, that include , , and . Docosahexaenoic acid is also important in biological systems, particularly with respect to sight.
Glycerolipids
Glycerolipids are composed of mono-, di-, and tri-substituted
,
the best-known being the fatty acid
Ester of glycerol, called
. The word "triacylglycerol" is sometimes used synonymously with "triglyceride". In these compounds, the three hydroxyl groups of glycerol are each esterified, typically by different fatty acids. Because they function as an energy store, these lipids comprise the bulk of storage
fat in animal tissues. The hydrolysis of the ester bonds of triglycerides and the release of glycerol and fatty acids from
adipose tissue are the initial steps in metabolizing fat.
Additional subclasses of glycerolipids are represented by glycosylglycerols, which are characterized by the presence of one or more monosaccharide attached to glycerol via a glycosidic linkage. Examples of structures in this category are the digalactosyldiacylglycerols found in plant membranes
Glycerophospholipids
Glycerophospholipids, usually referred to as
(though
are also classified as phospholipids), are ubiquitous in nature and are key components of the
lipid bilayer of cells,
as well as being involved in
metabolism and
cell signaling.
Neural tissue (including the brain) contains relatively high amounts of glycerophospholipids, and alterations in their composition has been implicated in various neurological disorders.
Glycerophospholipids may be subdivided into distinct classes, based on the nature of the polar headgroup at the
sn-3 position of the glycerol backbone in
and eubacteria, or the
sn-1 position in the case of
archaebacteria.
Examples of glycerophospholipids found in biological membranes are phosphatidylcholine (also known as PC, GPCho or lecithin), phosphatidylethanolamine (PE or GPEtn) and phosphatidylserine (PS or GPSer). In addition to serving as a primary component of cellular membranes and binding sites for intra- and intercellular proteins, some glycerophospholipids in eukaryotic cells, such as phosphatidylinositols and phosphatidic acids are either precursors of or, themselves, membrane-derived second messengers.
Sphingolipids
Sphingolipids are a complicated family of compounds
that share a common structural feature, a
sphingoid base backbone that is synthesized
de novo from the amino acid
serine and a long-chain fatty acyl CoA, then converted into
, phosphosphingolipids, glycosphingolipids and other compounds. The major sphingoid base of mammals is commonly referred to as
sphingosine. Ceramides (N-acyl-sphingoid bases) are a major subclass of sphingoid base derivatives with an
amide-linked fatty acid. The fatty acids are typically saturated or mono-unsaturated with chain lengths from 16 to 26 carbon atoms.
The major phosphosphingolipids of mammals are (ceramide phosphocholines),
Sterols
Sterols, such as
cholesterol and its derivatives, are an important component of membrane lipids,
along with the glycerophospholipids and sphingomyelins. Other examples of sterols are the
and their conjugates,
which in mammals are oxidized derivatives of cholesterol and are synthesized in the liver. The plant equivalents are the
phytosterols, such as β-sitosterol,
stigmasterol, and
brassicasterol; the latter compound is also used as a
biomarker for
algae growth.
The predominant sterol in
fungal cell membranes is
ergosterol.
Sterols are in which one of the hydrogen atoms is substituted with a hydroxyl group, at position 3 in the carbon chain. They have in common with steroids the same fused four-ring core structure. Steroids have different biological roles as and signaling molecules. The eighteen-carbon (C18) steroids include the estrogen family whereas the C19 steroids comprise the such as testosterone and androsterone. The C21 subclass includes the progestogens as well as the and mineralocorticoids.
Prenols
Prenol lipids are synthesized from the five-carbon-unit precursors isopentenyl diphosphate and dimethylallyl diphosphate, which are produced mainly via the
mevalonic acid (MVA) pathway.
The simple isoprenoids (linear alcohols, diphosphates, etc.) are formed by the successive addition of C5 units, and are classified according to number of these
terpene units. Structures containing greater than 40 carbons are known as polyterpenes.
are important simple isoprenoids that function as
and as precursors of
vitamin A.
Another biologically important class of molecules is exemplified by the
and
, which contain an isoprenoid tail attached to a quinonoid core of non-isoprenoid origin.
and
vitamin K, as well as the
, are examples of this class. Prokaryotes synthesize polyprenols (called
) in which the terminal isoprenoid unit attached to oxygen remains unsaturated, whereas in animal polyprenols (
) the terminal isoprenoid is reduced.
Saccharolipids
describe compounds in which fatty acids are linked to a sugar backbone, forming structures that are compatible with membrane bilayers. In the saccharolipids, a
monosaccharide substitutes for the glycerol backbone present in glycerolipids and glycerophospholipids. The most familiar saccharolipids are the acylated
glucosamine precursors of the
lipid A component of the lipopolysaccharides in Gram-negative bacteria. Typical lipid A molecules are
disaccharides of glucosamine, which are derivatized with as many as seven fatty-acyl chains. The minimal lipopolysaccharide required for growth in
Escherichia coli is Kdo
2-Lipid A, a hexa-acylated disaccharide of glucosamine that is glycosylated with two 3-deoxy-D-manno-octulosonic acid (Kdo) residues.
Polyketides
Polyketide are synthesized by polymerization of
acetyl and
Propionyl-CoA subunits by classic enzymes as well as iterative and multimodular enzymes that share mechanistic features with the fatty acid synthases. They comprise many secondary metabolites and
natural products from animal, plant, bacterial, fungal and marine sources, and have great structural diversity.
Many
are cyclic molecules whose backbones are often further modified by
glycosylation,
methylation,
hydroxylation,
oxidation, or other processes. Many commonly used
antimicrobial,
antiparasitic, and
anticancer agents are polyketides or polyketide derivatives, such as
, tetracyclines,
, and antitumor
.
Biological functions
Component of biological membranes
Eukaryote cells feature the compartmentalized membrane-bound
that carry out different biological functions. The glycerophospholipids are the main structural component of biological membranes, as the cellular
plasma membrane and the intracellular membranes of organelles; in animal cells, the plasma membrane physically separates the
intracellular components from the
extracellular environment. The glycerophospholipids are
amphipathic molecules (containing both hydrophobic and hydrophilic regions) that contain a glycerol core linked to two fatty acid-derived "tails" by ester linkages and to one "head" group by a
phosphate ester linkage. While glycerophospholipids are the major component of biological membranes, other non-glyceride lipid components such as
sphingomyelin and
(mainly cholesterol in animal cell membranes) are also found in biological membranes.
In plants and algae, the galactosyldiacylglycerols,
[Heinz E. (1996). "Plant glycolipids: structure, isolation and analysis", pp. 211–332 in Advances in Lipid Methodology, Vol. 3. W.W. Christie (ed.). Oily Press, Dundee. ] and sulfoquinovosyldiacylglycerol,
which lack a phosphate group, are important components of membranes of chloroplasts and related organelles and are among the most abundant lipids in photosynthetic tissues, including those of higher plants, algae and certain bacteria.
Plant thylakoid membranes have the largest lipid component of a non-bilayer forming monogalactosyl diglyceride (MGDG), and little phospholipids; despite this unique lipid composition, chloroplast thylakoid membranes have been shown to contain a dynamic lipid-bilayer matrix as revealed by magnetic resonance and electron microscope studies.
A biological membrane is a form of lamellar phase lipid bilayer. The formation of lipid bilayers is an energetically preferred process when the glycerophospholipids described above are in an aqueous environment.
The formation of lipids into protocell membranes represents a key step in models of abiogenesis, the origin of life.
Energy storage
Triglycerides, stored in adipose tissue, are a major form of energy storage both in animals and plants. They are a major source of energy in aerobic respiration. The complete oxidation of fatty acids releases about 38 kJ/g (9 kcal/g), compared with only 17 kJ/g (4 kcal/g) for the oxidative breakdown of
and
. The
adipocyte, or fat cell, is designed for continuous synthesis and breakdown of triglycerides in animals, with breakdown controlled mainly by the activation of hormone-sensitive enzyme
lipase.
Migratory birds that must fly long distances without eating use triglycerides to fuel their flights.
Signaling
Evidence has emerged showing that
lipid signaling is a vital part of the
cell signaling.
Lipid signaling may occur via activation of G protein-coupled or
, and members of several different lipid categories have been identified as signaling molecules and cellular messengers.
These include sphingosine-1-phosphate, a sphingolipid derived from ceramide that is a potent messenger molecule involved in regulating calcium mobilization,
cell growth, and apoptosis;
and the phosphatidylinositol phosphates (PIPs), involved in calcium-mediated activation of protein kinase C;
the
prostaglandins, which are one type of fatty-acid derived eicosanoid involved in
inflammation and immunity;
the steroid hormones such as
estrogen,
testosterone and
cortisol, which modulate a host of functions such as reproduction, metabolism and blood pressure; and the
such as 25-hydroxy-cholesterol that are liver X receptor
.
Phosphatidylserine lipids are known to be involved in signaling for the phagocytosis of apoptotic cells or pieces of cells. They accomplish this by being exposed to the extracellular face of the cell membrane after the inactivation of
which place them exclusively on the cytosolic side and the activation of scramblases, which scramble the orientation of the phospholipids. After this occurs, other cells recognize the phosphatidylserines and phagocytosize the cells or cell fragments exposing them.
Other functions
The "fat-soluble" vitamins (
retinol,
Calciferol,
tocopherol and
Phylloquinone) – which are
isoprene-based lipids – are essential nutrients stored in the liver and fatty tissues, with a diverse range of functions. Acyl-carnitines are involved in the transport and metabolism of fatty acids in and out of mitochondria, where they undergo
beta oxidation.
Polyprenols and their phosphorylated derivatives also play important transport roles, in this case the transport of
across membranes. Polyprenol phosphate sugars and polyprenol diphosphate sugars function in extra-cytoplasmic glycosylation reactions, in extracellular polysaccharide biosynthesis (for instance,
peptidoglycan polymerization in bacteria), and in eukaryotic protein N-
glycosylation.
are a subclass of glycerophospholipids containing four acyl chains and three glycerol groups that are particularly abundant in the inner mitochondrial membrane.
They are believed to activate enzymes involved with oxidative phosphorylation.
Lipids also form the basis of steroid hormones.
Metabolism
The major dietary lipids for humans and other animals are animal and plant triglycerides, sterols, and membrane phospholipids. The process of lipid metabolism synthesizes and degrades the lipid stores and produces the structural and functional lipids characteristic of individual tissues.
Biosynthesis
In animals, when there is an oversupply of dietary carbohydrate, the excess carbohydrate is converted to triglycerides. This involves the synthesis of fatty acids from
acetyl-CoA and the
esterification of fatty acids in the production of triglycerides, a process called
lipogenesis.
Fatty acids are made by fatty acid synthases that polymerize and then reduce acetyl-CoA units. The acyl chains in the fatty acids are extended by a cycle of reactions that add the acetyl group, reduce it to an alcohol, dehydrate it to an
alkene group and then reduce it again to an
alkane group. The enzymes of fatty acid biosynthesis are divided into two groups, in animals and fungi all these fatty acid synthase reactions are carried out by a single multifunctional protein,
while in plant
and bacteria separate enzymes perform each step in the pathway.
The fatty acids may be subsequently converted to triglycerides that are packaged in
lipoproteins and secreted from the liver.
The synthesis of unsaturated fatty acids involves a desaturase reaction, whereby a double bond is introduced into the fatty acyl chain. For example, in humans, the desaturation of stearic acid by stearoyl-CoA desaturase-1 produces oleic acid. The doubly unsaturated fatty acid linoleic acid as well as the triply unsaturated α-linolenic acid cannot be synthesized in mammalian tissues, and are therefore essential fatty acids and must be obtained from the diet.
Triglyceride synthesis takes place in the endoplasmic reticulum by metabolic pathways in which acyl groups in fatty acyl-CoAs are transferred to the hydroxyl groups of glycerol-3-phosphate and diacylglycerol.
and terpenoid, including the , are made by the assembly and modification of isoprene units donated from the reactive precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate.
Degradation
Beta oxidation is the metabolic process by which fatty acids are broken down in the
mitochondria or in
peroxisomes to generate
acetyl-CoA. For the most part, fatty acids are oxidized by a mechanism that is similar to, but not identical with, a reversal of the process of fatty acid synthesis. That is, two-carbon fragments are removed sequentially from the carboxyl end of the acid after steps of
dehydrogenation, hydration, and
oxidation to form a
keto acid, which is split by
thiolysis. The acetyl-CoA is then ultimately converted into adenosine triphosphate (ATP), CO
2, and H
2O using the citric acid cycle and the electron transport chain. Hence the citric acid cycle can start at acetyl-CoA when fat is being broken down for energy if there is little or no glucose available. The energy yield of the complete oxidation of the fatty acid palmitate is 106 ATP.
Unsaturated and odd-chain fatty acids require additional enzymatic steps for degradation.
Nutrition and health
Most of the fat found in food is in the form of triglycerides, cholesterol, and phospholipids. Some dietary fat is necessary to facilitate absorption of fat-soluble vitamins (
retinol,
calciferol,
tocopherol, and
phylloquinone) and
carotenoids.
Humans and other mammals have a dietary requirement for certain essential fatty acids, such as
linoleic acid (an omega-6 fatty acid) and alpha-linolenic acid (an omega-3 fatty acid) because they cannot be synthesized from simple precursors in the diet.
Both of these fatty acids are 18-carbon polyunsaturated fatty acids differing in the number and position of the double bonds. Most
are rich in linoleic acid (
Safflower oil,
sunflower oil, and
Corn oil oils). Alpha-linolenic acid is found in the green leaves of plants and in some seeds, nuts, and legumes (in particular
linseed oil,
rapeseed,
walnut, and
soy).
are particularly rich in the longer-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid.
Many studies have shown positive health benefits associated with consumption of omega-3 fatty acids on infant development, cancer, cardiovascular diseases, and various mental illnesses (such as depression, attention-deficit hyperactivity disorder, and dementia).
In contrast, it is now well-established that consumption of , such as those present in partially hydrogenated vegetable oils, are a risk factor for cardiovascular disease. Fats that are good for one may be turned into trans fats by improper cooking methods that result in overcooking the lipids.
A few studies have suggested that total dietary fat intake is linked to an increased risk of obesity.
See also
-
, a class of natural products composed of long aliphatic chains and phenolic rings that occur in plants, fungi and bacteria
Bibliography
External links
Introductory
Nomenclature
Databases
-
LIPID MAPS – Comprehensive lipid and lipid-associated gene/protein databases.
-
LipidBank – Japanese database of lipids and related properties, spectral data and references.
General
-
ApolloLipids – Provides dyslipidemia and cardiovascular disease prevention and treatment information as well as continuing medical education programs
-
National Lipid Association – Professional medical education organization for health care professionals who seek to prevent morbidity and mortality stemming from dyslipidemias and other cholesterol-related disorders.
