Energy economy of the cells Glucose --- ready cash Lipids --- savings account Fatty acids (from triacylglycerols) catabolization Citric acid cycle ATP Acetyl-CoA synthesis Lipids

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 acyltransferase Carnitine translocase

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 CH3(CH2)16C-S-CoA + 8FAD + 8NAD+ + 8H2O + 8CoA-SH 9CH3-C-S-CoA + 8FADH2 + 8NADH + 8H+ O 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 ● Most of the cholesterol formed in the smooth ER of the liver in mammals

The biosynthesis of mevalonate 2 acetyl-CoA ●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

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 amino acids Cholesterol ester fatty acids + cholesterol ACAT (acyl-CoA cholesterol acyltransferase) HMG-CoA reductase Synthesis of LDL receptors