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Energy economy of the cells Glucose --- ready cash Lipids --- savings account Fatty acids (from triacylglycerols) catabolization Acetyl-CoA synthesis Lipids Citric acid cycle ATP Catabolism of Lipids Phospholipiase D in spider and snake venom Lipid products of hydrolysis Lyse red blood cells Prevent clot formation Hormone-dependent hydrolysis of triacylglyerols The formation of an acetyl-CoA in cytosol (activation step requires two ATP) Role of carnitine in the transfer of acyl groups to the mitochondrial matrix Carnitine translocase Carnitine acyltransferase b-oxidation of saturated fatty acids One cycle: 2 C shorten 1 acetyl-CoA formed 1 FADH2 formed 1 NADH formed Degradation of stearic acid (18 C) through b-oxidation The energy yield from the oxidation of fatty acids O CH3(CH2)16C-S-CoA + 8FAD + 8NAD+ + 8H2O + 8CoA-SH O 9CH3-C-S-CoA + 8FADH2 + 8NADH + 8H+ O 9CH3-C-S-CoA + 9FAD + 27NAD + + 9GDP + 9Pi + 27 H2O 18CO2 + 9CoA-SH + 9FADH2 + 27NADH + 9GTP + 27H+ 17FADH2 + 8.5O2 + 25.5ADP + 25.5Pi 17 FAD + 25.5 ATP + 17 H2O 35NADH + 35H+ + 17.5 O2 + 87.5ADP + 87.5Pi 35NAD+ + 87.5ATP + 35H2O O CH3(CH2)16C-S-CoA + 26O2 + 122 ADP + 122Pi 18CO2 + 17H2O + 122ATP + CoA-SH one 18C fatty acid 120 ATP one 6C glucose 32 ATP The balance sheet for oxidation of one molecule of stearic acid Cytosol Matrix in mitochondia Citric acid cycle Electron transport chain O CH3(CH2)16C-S-CoA + 26O2 + 122 ADP + 122Pi 18CO2 + 17H2O + 122ATP + CoA-SH Metabolic water The oxidation of a fatty acid containing an odd number of carbon atoms b-oxidation of unsaturated fatty acids The oxidation pathways for polyunsaturated fatty acids The anabolism of fatty acids ● Oxaloacetate and acetyl-CoA can not cross through mitochondria membrane but citrate can. fatty acid synthesis in cytosol The formation of malonyl-CoA --the first step in anabolism of fatty acids Acetyl-CoA carboxylase Three proteins making up acetyl-CoA carboxylase The first cycle of palmitate synthesis ACP: acyl carrier protein Fatty acid synthase ACP has a functional group that is structurally similar to coenzyme A The second cycle of palmitate synthesis in E. coli 16C saturated fatty acid (palmitate) In E. coli, multienzyme system In eukaryotes, multifunctional enzyme A comparison of fatty acid degradation and biosynthesis Chain lengthening beyond 16C Pathways for the biosynthesis of triacylglycerols Pathways for the biosynthesis of phosphoacylglycerols (I) In E. coli Pathways for the biosynthesis of phosphoacylglycerols (II) In mammals The interconversion of PE and PS in mammals The anabolism of cholesterol C2 C6 C5 C30 C27 ● Most of the cholesterol formed in the smooth ER of the liver in mammals The biosynthesis of mevalonate ●This step is inhibited by high levels of cholesterol and is the major control point of cholesterol synthesis ●A target for drugs to lower cholesterol levels in the body ●lovastatin an inhibitor of HMG-CoA reductase 2 acetyl-CoA The synthesis of Squalene The synthesis of bile acids from cholesterol The synthesis of steroid hormones from cholesterol The role of cholesterol in heart disease ● Deposition of cholesterol plaques atherosclerosis ● Cholesterol is transported by lipoproteins in bloodstream ● Lipoprotein aggregates are classified by their densities LDL (low-density lipoproteins) particles Lipids: cholesterol triacylglycerols cholerserol esters phospholipids The fate of cholesterol in the cell lysosomes Proteins in LDL Cholesterol ester amino acids fatty acids + cholesterol ACAT (acyl-CoA cholesterol acyltransferase) HMG-CoA reductase Synthesis of LDL receptors