Lipid Metabolism Overview & Fatty Acid Synthesis PDF

LIPID METABOLISM OVERVIEW & FATTY ACID SYNTHESIS Lipid – non polar (hydrophobic) compound that is insoluble in water, but soluble in an organic solvent (e.g., ether, benzene, acetone, chloroform) Lipid -“lipid” is synonymous with “fat”, but also includes phospholipids, sterols, etc. ...

LIPID METABOLISM OVERVIEW & FATTY ACID SYNTHESIS Lipid – non polar (hydrophobic) compound that is insoluble in water, but soluble in an organic solvent (e.g., ether, benzene, acetone, chloroform) Lipid -“lipid” is synonymous with “fat”, but also includes phospholipids, sterols, etc.  FUNCTION Protoplasmic and Reserve Lipids Lipids are concentrated sources of ENERGY (1g – 9,3 kcal) Lipids in thermoregulation Lipids provide means whereby fat-soluble nutrients (e.g., sterols, vitamins) can be absorbed by the body Lipids are structural element of cell, subcellular components Lipid components lipoproteins; hormones and precursors for prostaglandin synthesis Nonpolar lipids act as electrical insulators, allowing rapid propagation of depolarization waves along myelinated nerves. Lipids are transported in the blood combined with proteins in lipoprotein particles. Lipids have essential roles in nutrition and health and knowledge of lipid biochemistry is necessary for the understanding of many important biomedical conditions, including: obesity, diabetes mellitus, atherosclerosis, cardiovascular disease, rheumatoid arthritis, dementia etc.  CLASSIFICATION OF LIPIDS Simple 1. Acylglyceroles 2. Waxes Complex 1. Phospholipids 1.1. Glycerophospholipids 1.2. Sphingophsopholipids 2. Glycolipids Sterols; Cholesterol, Hormones, Vit.D, Bile Acids Lipid Derivatives; Eicosanoids, Polyisoprenoids, Ketone bodies  Fatty acids are aliphatic carboxylic acids; Fatty acids occur in the body mainly as esters in natural fats and oils, but are found in the unesterified form as free acids; Fatty acids that occur in natural fats usually contain an even number of carbon atoms; The chain may be saturated (containing no double bonds) or unsaturated (containing one or more double bonds).  Fatty acids 1. Monounsaturated fatty acids, containing one double bond. 2. Polyunsaturated fatty acids, containing two or more double bonds. Oleic acid – 18-carbon, monounsaturated Linoleic acid – 18-carbon, polyunsaturated  Fatty acids consist of alkyl chain with terminal carboxyl group (COOH) which ionizes, becoming –COO-. Fatty acids have amphoteric nature. GLYCEROPHOSPHOLIPIDS (Amphipathic) Systematic nomenclature  TRIACYLGLYCEROLS Reserve=Storage Lipids Phospholipids 14  Phospholipids are main lipid constituents of membranes Phosphatidilcholine represent a large proportion of the body’s store of choline (a source of methyl groups needed for many steps in metabolism. Its important in nervous transmission as a acetylcholine). Phosphatidilethanolamine (cephalin) Phosphatidilserine (plays a role in apoptosis, programmed cell death). Phosphatidileinositol is involced in cell signaling Cardiolipin (Diphosphatidylglycerol) is a major lipid of mitochondrial membranes. Glycolipids (glycosphingolipids) are widely distributed in every tissue of the body, particularly in nervous tissue, such as brain. They occur in the outer leaflet of the plasma membrane, where they contribute to cell membrane carbohydrates.  CHOLESTEROL Textbook of Biochemistry with Clinical Correlations, 7e edited by Thomas M. Devlin © 2011 John Wiley & Sons, Inc.  FA supplied by the diet; Carbohydrates and proteins can be converted to FA, which are stored as TAG; FA synthesis (Lipogenesis) occurs primarily in the liver and lactating mammary glands and, to a lesser extent, in adipose tissue; Lipogenesis uses ATP and NADPH; Lipogenesis in totally cytosolic process  SYNTHESIS OF FATTY ACIDS: LIPOGENESIS ACC Biotin dependent enzyme ACC is feedforward activated by citrate and inhibited by feedback inhibition fatty acids. Insulin activates ACC Glucagon inhibits ACC  SYNTHESIS OF FATTY ACIDS: LIPOGENESIS Palmitic acid (16:00) synthesis occurs through a series of reactions involving the repeated addition of two-carbon units from malonyl- CoA to a growing fatty acid chain. Each cycle involves several enzymatic reactions, including condensation, reduction, dehydration, and reduction again. These reactions are catalyzed by a multi- enzyme complex called fatty acid synthase (FAS). Acyl carrier protein (ACP) is a cofactor of fatty acid biosynthesis. ACP is the phosphopantetheine-containing (B5) domain of eukaryotic FAS. Each cycle adds two carbons to the growing fatty acid chain, and the process continues until palmitic acid (a 16-carbon saturated fatty acid) is formed. Typically around 7 cycles are performed. Further elongation of fatty acid chains Although palmitate, a 16-carbon, fully saturated long-chain length fatty acid (16:0), is the primary end product of fatty acid synthase activity, it can be further elongated by the addition of two-carbon units in the smooth endoplasmic reticulum (SER). Acyl-CoA or Malonyl-CoA molecules serve as the starting point for elongation. NADPH supplies the electrons. The brain has additional elongation capabilities, allowing it to produce the very-long-chain fatty acids (over 22 carbons) that are required for synthesis of brain lipids. Desaturation of fatty acid chains Enzymes (desaturases) also present in the SER are responsible for desaturating long-chain fatty acids. The desaturation reactions require NADH, cytochrome b5 and its FAD-linked reductase.