Lipids PDF

Lipids Dr. Marie Kuan Yin Oking Associate Professor of Biochemistry Davao Doctors College BSN 11J Overview The lipids are heterogeneous compounds, which are insoluble in water but soluble in non-polar solvents such as ether, chloroform and benzene. Biological Role of Lipid...

Lipids Dr. Marie Kuan Yin Oking Associate Professor of Biochemistry Davao Doctors College BSN 11J Overview The lipids are heterogeneous compounds, which are insoluble in water but soluble in non-polar solvents such as ether, chloroform and benzene. Biological Role of Lipids 1) components of membranes 2) major storage form of carbon and energy 3) precursors of other important substances, i.e., vitamins and Steroid hormones 4) insulation barriers to avoid thermal, electrical, and physical shock 5) as lipoproteins that transport lipids in the blood 6) natural appetite stimulant o FUEL. Fat is most concentrated storage form of potential energy o INSULATOR. Fat is а bad conductor of heat, it provides excellent insulation o PROTECTION. Fat may also provide padding to protect the internal organs. o BUILDING BLOCKS. Some compounds derived from lipids are important building blocks of biologically active materials (hormones, vitamins, secondary messengers) o STRUCTURAL. Lipoproteins and phospholipids are constituents of cell membrane MAJOR LIPIDS AND METABOLIC FUNCTIONS 1) Fatty acids 2) Triacylglycerols 3) Phospholipids 4) Glycerophospholipids 5) Sphingophospholipids 6) Glycosphingolipids 7) Cholesterol Fatty acids long chain aliphatic carboxylic acid: products obtained from the hydrolysis of lipids Occur in plant and animal foods; also exhibit complex forms with other substances. Obtained from hydrolysis of fats; usually contains an even number of carbon atoms and are straight chain derivatives Classification of fatty acids is based on the length of the carbon chain (short, medium, or long); the number of double bonds (unsaturated, mono-, or polyunsaturated); or essentiality in the diet (essential or nonessential) Triacylglycerols 3 molecules of fatty acid esterified to a molecule of glycerol “Neutral fat”- stored in adipose tissue as oily droplet (i.e., Body’s major fuel storage reserve) Main storage form of fatty acids Concentrated stores of metabolic energy Adipose Tissue- synthesis, storage, and hydrolysis of TAG Liver- TAG synthesis primarily for production of plasma lipoproteins, rather than for energy storage Phospholipids polar, ionic molecules composed of an alcohol that is attached by a phosphodiester bridge to either diacylglycerol or sphingosine -amphipathic with a hydrophilic head and long, hydrophobic tail predominant lipids of cell membrane, component of lung surfactant and bile Sphingophospholipids sphingomyelin: the only significant sphingophospholipid in human as it is an important constituent of the myelin sheath backbone is the amino alcohol sphingosine Glycosphingolipids -aka glycolipids - differ from sphingophospholipid in that they do not contain phosphate and the polar head function is provided by a monosaccharide or oligosaccharide attached directly to the ceramide -classified as either neutral or acidic glycosphingolipids -cerebrosides are the simplest neutral glycosphingolipids with the alcohol group attached to monosaccharides charged at physiologic pH due to the presence of N-acetylneuraminic acid (NANA) in gangliosides or by sulfate groups in sulfatides G. Gangliosides are derivatives of ceramide oligosaccharides and contain one or more NANA Cholesterol structural component of cell membrane, precursor of hormones, bile and vitamins consists of four fused hydrocarbon rings (A-D) and has an eight-carbon, branched hydrocarbon attached to carbon 17 of the D ring, a hydroxyl group at carbon 3 of ring A and a double bond between carbon 5 and 6 in ring B TRIACYLGLYCEROL SYNTHESIS Fatty acids are stored as triacylglycerols Three fatty acids esterified to a molecule of glycerol TAGs are synthesized by: o Sequential addition of two fatty acyl CoA to glycerol-3- phosphate o Removal of phosphate o Addition of the third fatty acyl CoA SOURCES OF GLYCEROL-3-PHOSPHATE: DHAP from glycolysis o Enzyme: Glycerol-3-phosphate dehydrogenase o Present in liver and adipose tissue Phosphorylation of free glycerol o Enyzme: Glycerol kinase o Present in liver only MOBILIZATION OF STORED FATS During a fast, stored fat is hydrolyzed to release fatty acids and glycerol from their TAG form Triacylglycerol = Glycerol + 3 Fatty Acids Enzyme: Hormone-sensitive lipase Removes fatty acid from carbon 1 and/or carbon 3 Activated by glucagon and epinephrine (phosphorylation) Inhibited by insulin (dephosphorylation) Additional lipases remove the remaining fatty acids BETA OXIDATION What is it for? o Removal of acetyl CoA fragments from the ends of fatty acids, also yielding NADH and FADH2 in the process ○ § Acetyl CoA can enter the citric acid cycle ○ § NADH and FADH2 can enter the ETC Where does it occur? o Tissues that can use fatty acids as energy source, primarily muscle and liver o Fatty acid activation occurs in the cytosol o β-oxidation occurs in the mitochondria What is the substrate? o Palmitate What are the products? 8 Acetyl CoA, 7 NADH, 7 FADH2 Which step is rate-limiting? Translocation of fatty acyl CoA from the cytosol to the mitochondria Enzyme: Carnitine-palmitoyl transferase FATTY ACIDS WITH AN ODD NUMBER OF CARBONS Oxidation of a fatty acid with an odd number of carbon atoms will yield acetyl CoA and a molecule of propionyl CoA Propionyl CoA is converted to succinyl CoA, a TCA intermediate Sequential enzymes: o Propionyl CoA carboxylase requires Biotin (B7) o Methylmalonyl CoA mutase requires Cobalamin vitamin B12 VERY LONG CHAIN FATTY ACIDS Peroxisomes oxidize very long chains of fatty acids (C20, C22) Oxidation of unsaturated FAs require an additional enzyme (3,2 enoyl-CoA isomerase) Peroxisomes oxidize very long chains of fatty acids (C20, C22) Oxidation of unsaturated FAs require an additional enzyme (3,2 enoyl-CoA isomerase) LIPID MALABSORPTION Manifests as steatorrhea Results in deficiency in fat-soluble vitamins and essential fatty acids Possible causes: Liver disease Pancreatic disease Cholelithiasis Shortened bowel Intestinal mucosal defects