Lipid

Lipids are broadly defined as any fat-soluble (signaling molecules. The smooth endoplasmic reticulum also processes these lipids, which store energy.

Although the term lipid is sometimes used as a synonym for fat, fats are in fact a subgroup of lipids called cholesterol.

Lipids are a diverse and ubiquitous group of compounds which have many key biological functions, such as acting as structural components of cell membranes, serving as energy storage sources and participating in signaling pathways. Lipids may be broadly defined as hydrophobic or amphipathic small molecules that originate entirely or in part from two distinct types of biochemical subunits or "building blocks": ketoacyl and isoprene groups.^[2] Using this approach, lipids may be divided into eight categories : Fatty Acyls, Glycerolipids, Glycerophospholipids, Sphingolipids, Saccharolipids and Polyketides (derived from condensation of ketoacyl subunits); and Sterol Lipids and Prenol Lipids (derived from condensation of isoprene subunits). Although the term lipid is sometimes used as a synonym for fat, fats are generally triesters of fatty acids and are covered by a category of lipids called Glycerolipids (which include mono-, di- and triglycerides).

Categories of Lipids

Fatty Acyls (including fatty acids) are a diverse group of molecules synthesized by chain-elongation of an anandamide.

Glycerolipids are composed mainly of mono-, di- and tri-substituted glycerols,^[5] the most well-known being the fatty acid esters of glycerol (triacylglycerols), also known as triglycerides. these comprise the bulk of storage fat in animal tissues. Additional subclasses are represented by glycosylglycerols, which are characterized by the presence of one or more sugar residues attached to glycerol via a glycosidic linkage. Examples of structures in this category are the digalactosyldiacylglycerols found in plant membranes and seminolipid from mammalian spermatazoa.

Glycerophospholipids, also referred to as 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 are themselves, membrane-derived second messengers. Typically one or both of these hydroxyl groups are acylated with long-chain fatty acids, but there are also alkyl-linked and 1Z-alkenyl-linked (plasmalogen) glycerophospholipids, as well as dialkylether variants in prokaryotes.

Sphingolipids are a complex family of compounds^[7] that share a common structural feature, a sphingoid base backbone that is synthesized de novo from serine and a long-chain fatty acyl CoA, then converted into ceramides, phosphosphingolipids, glycosphingolipids and other species. 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 14 to 26 carbon atoms. The major phosphosphingolipids of mammals are sphingomyelins (ceramide phosphocholines), whereas insects contain mainly ceramide phosphoethanolamines and fungi have phytoceramidephosphoinositols and mannose containing headgroups. The Glycosphingolipids are a diverse family of molecules composed of one or more sugar residues linked via a glycosidic bond to the sphingoid base. Examples of these are the simple and complex glycosphingolipids such as cerebrosides and gangliosides.

Sterol lipids, such as Vitamin D, are characterized by cleavage of the B ring of the core structure. Other examples of sterols are the bile acids and their conjugates,^[9] which in mammals are oxidized derivatives of cholesterol and are synthesized in the liver.

Prenol lipids are synthesized from the 5-carbon precursors isopentenyl diphosphate and dimethylallyl diphosphate that are produced mainly via the mevalonic acid (MVA) pathway^[10]. The simple isoprenoids (linear alcohols, diphosphates, etc.) are formed by the successive addition of C5 units, and are classified according to number of these Vitamin K, as well as the ubiquinones, are examples of this class. Bacteria synthesize polyprenols (called bactoprenols) in which the terminal isoprenoid unit attached to oxygen remains unsaturated, whereas in animal polyprenols (dolichols) the terminal isoprenoid is reduced.

Saccharolipids describe compounds in which fatty acids are linked directly to a sugar backbone, forming structures that are compatible with membrane bilayers. In the saccharolipids, a sugar substitutes for the glycerol backbone that is present in glycerolipids and glycerophospholipids. The most familiar saccharolipids are the acylated 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 E. coli is Kdo₂-Lipid A, a hexa-acylated disaccharide of glucosamine that is glycosylated with two 3-deoxy-D-manno-octulosonic acid (Kdo) residues.^[11]

Polyketides are synthesized by polymerization of acetyl and propionyl subunits by classic enzymes as well as iterative and multimodular enzymes that share mechanistic features with the fatty acid synthases. They comprise a very large number of secondary metabolites and natural products from animal, plant, bacterial, fungal and marine sources, and have great structural diversity.^[12] Many epothilones.

Biological Functions

Membranes

The cholesterol in animal cell membranes) are also found in biological membranes. In plants and algae, the galactosyldiacylglycerols,^[13] and sulfoquinovosyldiacylglycerol,^[14] which lack a phosphate group, are important components of membranes of chloroplasts and related organelles and are the most abundant lipids in photosynthetic tissues, including those of higher plants, algae and certain bacteria.

A biological membrane is a form of lipid bilayer, as is a liposome. The formation of lipid bilayers is an energetically-preferred process when the Phase behaviour is a complicated area within biophysics and is the subject of current academic research. Micelles and bilayers form in the polar medium by a process known as the clathrate" cage around the dissolved lipophilic molecule.^[16]

Energy storage and metabolism

Triacylglycerols, stored in adipose tissue, are a major form of energy storage in animals. Animals use triglycerides for energy storage because of its high caloric content (9 KCal/g), whereas plants, which do not require energy for movement, can afford to store food for energy in a less compact but more easily accessible form, such as starch (carbohydrate). Triglycerides and phospholipids are broken down into free fatty acids by the action of lipases. lipoproteins (VLDL's) and secreted from the liver.

Signaling

In recent years, evidence has emerged showing that Liver X receptor (LXR) agonists.

Other functions

The "fat-soluble" vitamins (A, D, E and K) which are isoprene-based lipids are essential nutrients stored in the liver and fatty tissues. These have a diverse range of functions discussed elsewhere. Acyl-carnitines are involved in the transport and metabolism of fatty acids in and out of mitochondria, where they undergo beat oxidation. Polyprenols and their phosphorylated derivatives also play important transport roles, in this case the transport of oligosaccharides across membranes. Polyprenol phosphate sugars and polyprenol diphosphate sugars function in extra-cytoplasmic glycosylation reactions, in extra-cellular polysaccharide biosynthesis (for instance peptidoglycan polymerization in bacteria, and in eukaryotic protein N-glycosylation.^[20] Cardiolipins 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 invoved with oxidative phosphorylation.^[21]

Nutrition and health

Lipids play diverse and important roles in nutrition and health.^[22] Many lipids are absolutely essential for life. However, there is also considerable awareness that abnormal levels of certain lipids, particularly cholesterol (in hypercholesterolemia) and trans fatty acids, are risk factors for heart disease amongst others.

Humans have a requirement for certain essential fatty acids, such as docosahexaenoic acid (DHA). Most of the lipid found in food is in the form of triacylglycerols, cholesterol and phospholipids.

Most of the saturated fatty acids (as triacylglycerols) in the diet are incorporated into adipose tissue stores, because the absence of double bonds allows a higher energy yield per carbon than is obtained from oxidation of unsaturated fatty acids. The longer chain fatty acids are incorporated into cell membranes as phospholipids regardless of degree of saturation. Since dietary fatty acids are exchanged with membrane fatty acids, dietary fat composition is reflected in membrane lipid composition. Thus dietary fatty acids can influence cell function through effects on membrane properties. Dietary fat provides an average energy intake which is approximately twice that of carbohydrate or protein. A minimum amount of dietary fat is necessary to facilitate absorption of fat-soluble vitamins (A, D, E and K) and carotenoids. A minimal amount of body fat is also necessary to provide insulation that prevents heat loss and protects vital organs from shock due to ordinary activities.

High fat intake contributes to increased risk of obesity, diabetes and atherosclerosis. Atherosclerosis is the primary cause of coronary and cardiovascular diseases and is primarly due to the buildup of plaque on the inside walls of arteries. Plaque is made up of cholesterol-rich low density lipoproteins (LDL), macrophages, smooth muscle cells, platelets, and other substances. In North America and most other western countries, atherosclerosis is the leading cause of illness and death, almost doubling the number of deaths from cancers. Despite significant medical advances, coronary artery disease and atherosclerotic stroke are responsible for more deaths than all other causes combined.A substantial amount of scientific evidence supports the impact of dietary fatty acids on cardiovascular health. Saturated fats have a profound hypercholesterolemic (increase blood cholesterol levels) effect and tend to increase plasma LDL. They are found predominantly in animal products (butter, cheese and meat) but coconut oil and palm oil are common vegetable sources. Intake of monounsaturated fats in oils such as olive oil is thought to be preferable to consumption of polyunsaturated fats in oils such as corn oil because the monounsaturated fats apparently do not lower high-density-lipoprotein (HDL) cholesterol levels.^[23] Keeping cholesterol in the normal range not only helps prevent heart attacks and strokes but may also prevent the progression of atherosclerosis. "Statins" are a class of drugs that lowers the level of cholesterol in the blood by inhibiting the enzyme HMG-CoA reductase. This is a key enzyme involved in the biosynthesis of cholesterol in the liver.

References

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^ Coleman, R.A. and Lee, D.P. (2004). "Enzymes of triacylglycerol synthesis and their regulation". Prog. Lipid Res. 43: 134-176.
^ Ivanova, P., Milne, S., Byrne, M. O., Xiang, Y., and Brown, H. A.(2007) "Glycerophospholipid identification and quantitation by electrospray mass spectrometry" in Meth. Enzymol., Academic Press, 432, 21-57 http://dx.doi.org/10.1016/S0076-6879(07)32002-8
^ Merrill, A.H., Jr. and Sandhoff, K.(2002) "Sphingolipids: metabolism and cell signaling",in New Comprehensive Biochemistry: Biochemistry of Lipids,Lipoproteins,and Membranes, Vance, D.E. and Vance, J.E., eds. Elsevier Science, NY. Ch. 14.
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^ Kuzuyama, T. and Seto, H. (2003). "Diversity of the biosynthesis of the isoprene units.". Nat.Prod Rep. 20: 171-183.
^ Raetz, C. R., Garrett, T. A., Reynolds, C. M., et al (2006). "Kdo2-Lipid A of Escherichia coli, a defined endotoxin that activates macrophages via TLR-4". J. Lipid Res. 47: 1097-1111. PMID 16479018.
^ Walsh, C.T. (2004). "Polyketide and nonribosomal peptide antibiotics: modularity and versatility". Science. 303: 1805-1810.
^ Heinz, E.(1996) Plant glycolipids: structure, isolation and analysis. in Advances in Lipid Methodology - 3, pp. 211-332 (ed. W.W. Christie, Oily Press, Dundee)
^ Hölzl, G. and Dörmann, P. (2007). "Structure and function of glycoglycerolipids in plants and bacteria". Prog. Lipid Res. 46: 225-243.
^ Wiggins PM (1990). "Role of water in some biological processes". Microbiol. Rev. 54 (4): 432-49. PMID 2087221.
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^ Berg, J.M., Tymoczko, J.L., Stryer, L.(2006) Biochemistry, Freeman, New York.5th ed. ISBN 0716787245
^ Wang X (2004). "Lipid signaling". Curr. Opin. Plant Biol. 7 (3): 329-36. PMID 15134755.
^ Eyster,K.M. (2007). "The membrane and lipids as integral participants in signal transduction". Adv. Physiol. Edu. 31: 5-16.
^ Helenius, A., Aebi, M. (2001). "Intracellular functions of N-linked glycans". Science 291: 2364-2369. PMID 11269317.
^ Hoch, FL (1992). "Cardiolipins and biomembrane function". Biochim. Biophys. Acta. 1113 (1): 71-133. PMID 10206472.
^ Spiller, G.A. ed., (2006), Handbook of Lipids in Human Nutrition,Boca Raton: CRC Press.
^ Dreon, D.M., Vranizan, K.M., Krauss, R.M., Austin, M.A., Wood, P.D. (1990). "The effects of polyunsaturated fat vs monounsaturated fat on plasma lipoproteins". JAMA 263 (18): 2462-6. PMID 2329634.