Metabolism of Lipids PDF

Metabolism of Lipids Xin Liu Ph.D. Department of Biochemistry and Molecular Biology Tianjin Medical University Email: [email protected] 1 2  1. How many molecules of ATP are generated or...

Metabolism of Lipids Xin Liu Ph.D. Department of Biochemistry and Molecular Biology Tianjin Medical University Email: [email protected] 1 2  1. How many molecules of ATP are generated or consumed? 2. Why these pathways are essential/significant for Glycolysis the metabolism of carbohydrates (glucose)? Citric acid cycle 3. Why the following molecules are very Glycogen important for the metabolic pathway? Gluconeogenesis Glucose-6-P, Pyruvate, Acetyl-CoA, Lactate, Pentose phosphate pathway 4. Regulation 3  Words you may confuse….. Synthases and Synthetases Ligases & Lyases Kinases, Phosphatases, and Phosphorylases: 4 Synthases catalyze condensation reactions in which no nucleoside triphosphate (ATP, GTP, and so forth) is required as an energy source. Citrate synthase Synthetases catalyze condensations that do use ATP or another nucleoside triphosphate as a source of energy for the synthetic reaction. Succinyl-CoA synthetase is such an enzyme. Ligases (from the Latin ligare, “to tie together”) are enzymes that catalyze condensation reactions in which two atoms are joined using ATP or another energy source. (Thus synthetases are ligases.) DNA ligase. Lyases, enzymes that catalyze cleavages(or, in the reverse direction, additions) in which electronic rearrangements occur. The PDH complex, which oxidatively cleaves CO2 from pyruvate, is a member of the large class of lyases. ATP-citrate lyase 5 Kinase applied to enzymes that transfer a phosphoryl group from a nucleoside triphosphate such as ATP to an acceptor molecule—a sugar(as in hexokinase and glucokinase), a protein (as in glycogen phosphorylase kinase), another nucleotide (as in nucleoside diphosphate kinase), or a metabolic intermediate such as oxaloacetate (as in PEP carboxykinase). The reaction catalyzed by a kinase is a phosphorylation. 6 Phosphorylase phosphorolysis, a displacement reaction in which phosphate is the attacking species and becomes covalently attached at the point of bond breakage. Such reactions are catalyzed by phosphorylases. Glycogen phosphorylase, for example, catalyzes the phosphorolysis of glycogen, producing glucose 1- phosphate. Phosphatase Dephosphorylation,the removal of a phosphoryl group from a phosphate ester, is catalyzed by phosphatases. 7 Metabolism of Lipids Triacylglycerol Lipid Transport and Storage Cholesterol 8  Metabolism of Lipids Lipids are a heterogeneous group of water- insoluble (hydrophobic) organic molecules that can be extracted from tissues by nonpolar solvents. Fats (triacylglycerol), cholesterol, cholesterol ester, phospolipids, glycolipids. 9 10 A. Common properties 1. Insoluble in water 2. Soluble in nonpolar solvents B. Classification of lipids Fats: esters of fatty acids with glycerol 11  Main functions of lipids  Fats are ideal storage molecules.  Cholesterols are source of bile salts and steroid hormones.  Phospholipids are essential component of cellular membranes. 12  Triacylglycerols Provide Stored Energy and Insulation  Vertebrates store TAGs as lipid droplets in adipocytes  Advantages to using TAGs as stored fuels ---carbon atoms of FAs are more reduced than those of sugars, oxidation of FAs yields more energy. ---the organism does not have to carry the extra weight of water hydration like polysaccharides 13 FIGURE 10.10 Structure of a typical cell membrane. Biochemistry 4th , PEARSON 14 FATs ( Triacylglycerol) 15  Fatty Acid ( FA ) Unesterified form usually contain an even number of carbon atoms. FFA is also a transport form found in plasma. Saturated F.A: no double bonds 16C Palmitic acid ; 18C Stearic acid Unsaturated F.A: contain one or more double bonds Palmitoleic acid; Oleic acid; Linoleic acid; Arachidonic acid 16 17 Numbering of unsaturated F.A  numbering system numbering is from the carboxyl group Linoleic acid – 18:2:  9,  12  numbering system numbering is from the methyl carbon, -3, - 6. 18 19 Most naturally occurring unsaturated F.A have cis -double bonds. cis - configuration (The acyl chain are on the same side of the double bonds) trans – configuration trans FA associate with elevated risk of cardiovascular disease. 20 21  Monounsaturated acids Palmitoleic acid 16:1:9 棕榈油酸 Oleic acid 18:1: 9油酸 Elaidic acid 18:1:9 (trans)反油酸 Polyunsaturated acids (PUFA) Linoleic acid 18:2: 9,12亚油酸 Linolenic acid 18:3: 9,12,15亚麻酸 22 Biochemistry 4th , PEARSON 23 24  Eicosanoids (eicosa-20 carbons) Eicosanoids are very potent, short-lived chemical signals derived from Arachidonic Acid(花生四烯酸)  Prostaglandins (PG)前列腺素  Thromboxanes (TX)血栓素  Leukotrienes (LT)白三烯 25 PG--- local hormones Wide variety of efforts of PGs: inflammation, smooth muscle contraction, sodium and water retention, platelet aggregation, gastric secretion. 26 27  TX TXA2 produced in platelets, causes arteriole contraction and platelet aggregation, lead to prolonged clotting time.  LT Involved in allergic reactions chemotaxis of white blood cells, inflammation. 28 Membrane phospholipids 29  Physical and chemical properties of F.A Fatty acids are amphipathic, form spherical micelles. 30 31  Physical and chemical properties of F.A Fatty acids are amphipathic, form spherical micelles. Melting points are strongly influenced by length and degree of unsaturation of hydrocarbon chain. Unsaturated F.A can be converted to saturated F.A through hydrogenation. 32 33  Phospholipids Glycerophospholipids 34 35  Phospholipids Phospholipids have phosphate and unsaturated or saturated F.A esterified to glycerol. Phospholipids and Respairatory Distress Syndrome  Lack of surfactant production in the lung of infants.  The major component of lung surfactant are phospholipids, especially of the phosphatidyl choline. 36 37  Phospholipids Sphingophospholipids 38  Phospholipids Functions 1.The major component of cellular membranes. 2. Store some unsaturated F.A. 39  Glycolipids Contain a F.A, sphingosine and carbohydrate  Cholesterol and cholesterol esters 40 41  Lipoprotein  Specific combinations of noncovalently associated lipids and protein.  Forms of transportation in plasma.  Help maintain the lipids in emulsified form.  Some 500mg of total lipids per 100ml of human blood in the postabsorptive state. TAG = 120mg Cholesterol = 220mg (2/3 cholesterol ester, 1/3 free cholesterol), PL+phosphatidylcholine + phosphatidylethanolamine = 160mg 42 43  Digestion, Absorption, Secretion, And Utilization of Dietary Lipids Sources of fats  Fats in the diet.  Fats stored in tissues.  Fats synthesized in Human energy : organs.  40% by dietary triacylglycerols.  More than 50% of energy of liver, heart, and resting skeletal muscle are from triacylglycerols. 44 The digestion of dietary lipids An adult ingests about 60 to 150 g of lipids per day  90% triacylglycerol  Cholesterol,cholesteryl esters, phospholipids, and unesterified ("free") fatty acids. 45  Processing of dietary lipid in the stomach Triacylglycerols (TAG) obtained from milk contain short- to medium-chain length fatty acids that can be degraded in the stomach by the acid lipases (lingual lipase and gastric lipase). 46 Emulsification of dietary lipid in the small intestine  Mechanisms use of the detergent properties of the bile salts.  Mechanical mixing due to peristalsis. 47 Action of bile salts in emulsifying fats in the intestine 48  Degradation of dietary lipids by pancreatic enzymes Substrates: Cholesteryl esters (CE), phospholipids (PL), and TAG containing LCFAs Enzymes: Pancreatic Lipase, Phospholipase , Cholesterol esterase. 49  The products of the degradation  Monoacylglycerol  Unesterified cholesterol  Free fatty acids + some fragments remaining from PL digestion +fat-soluble vitamins → micelles 50 51 Overview of fat digestion, absorption, storge and mobilization in the human 52 53 54 TAG+CE+PL+ apolipoprotein B-48 chylomicrons lymph blood peripheral tissues 55