Lipid metabolism

Roles of lipids Largest energy store Insulation Structural components Membranes Hormones Carrier Fat-soluble vitamins

Types of lipids Simple lipids Triglyceride Mostly triglycerides Principal storage form >95% of body fat Mostly in adipose cells Some in liver and skeletal muscle Triglyceride One glycerol 3 fatty acids All have linear C chain 14-22 C long Saturated or unsaturated

Types of lipids Compound lipids Neutral fats with other chemicals Glycolipids Sphingolipids Phosphoglycerides Lipoproteins Glycerol, two fatty acids and one sugar group Involved in cell recognition One fatty acid and one molecule of sphingosine Sphingomyelin Signal transmission and cell recognition Glycerol, two fatty acids, one phosphate group and one alcohol group Important component of cell membranes

Lipoproteins Formed mainly in the liver Consist of Triglycerides Phospholipids Cholesterol Protein Main transport form of lipids in the blood Fats are insoluble in water The protein and phospholipids allow the insoluble fatty acids to be carried in the core of the lipoprotein

Lipoproteins Classified according to their density HDL: Least amount of cholesterol Carry cholesterol back to the liver Converted to bile Most recycled, some excreted

Lipoproteins LDL and VLDL: Chylomicrons: Carry most of the cholesterol Have the greatest affinity for the arterial walls Particularly oxidized LDL Chylomicrons: Largest amount of triglycerides Produced in small intestinal cells Elevated after high fat meals

Lipid metabolism Triglycerides Not taken up directly into the cells Must be broken down first Fatty acids and glycerol Lipoprotein lipase Located on capillary endothelium Glycerol goes to liver

Lipid metabolism Phospholipase A2 Capillary endothelium Breaks down surface lipoproteins Lecithin-cholesterol acyltransferase (LCAT) Plasma Forms a fatty acid-cholesterol ester This is transferred to chylomicron or VLDL Helps maintain stability of those molecules as triglycerides are removed Lipid metabolism

Derived lipids Cholesterol Only in animal products In every cell of the body Cell membrane Vitamin D Hormones Testosterone Estrogen Cortisol Bile Fat metabolism Found in Egg yolks Meats, shellfish and dairy Diets high in saturated fats Increase cholesterol synthesis

Fatty acid synthesis Occurs in the liver and adipose tissue Essentially Acetyl-CoA + 7 Malonyl-CoA + NADPH + 14H+ → Palmitic Acid + 8CoA + 14 NADP+ + 6H2O Acetyl-CoA and Malonyl-CoA are reduced to Palmitic acid NADPH is the reducing agent Dehydration Rx Malonyl-CoA Created from Acetyl-CoA Acetyl-CoA carboxylase Thus, anything that increases Acetyl-CoA levels can lead to fat synthesis

Triglyceride synthesis Fatty acyl CoA

Triglyceride synthesis Glycerol 3 phosphate + 2 Fatty acyl-CoA Phosphatidic acid Phosphatidic acid converted to diacylglycerol Phosphatase Diacylglcerol + fatt acyl CoA Triglyceride Acyl transferase

Triglyceride metabolism Stored in Adipose tissue, liver, muscle Breakdown process Lipolysis Whether or not triglycerides come from muscle or liver, same basic steps occur Mobilization Circulation Uptake Activation Translocation B-oxidation Aerobic metabolism

Lipid mobilization Hormone sensitive lipase Fatty acids Breaks down stored triglycerides Fatty acids and glycerol released Into blood (adipose tissue) Glycerol Goes to liver Gluconeogenesis Glycogenesis Lipid biosynthesis Fatty acids Require a carrier Albumin

Lipid Mobilization Activation of Hormone sensitive lipase Epinephrine Activates G protein Stimulates adenylate cyclase Adenylate cyclase Produces cAMP Activates Protein kinase A

Lipid circulation Fatty acids bound to albumin Circulate around to active tissues How do they know?

Fatty acid uptake Uptake Directly related to circulating concentration Rate of blood flow Increased flow, increased delivery, increased uptake and utilization Requires Fatty acid transporter (FAT) and Fatty acid binding protein (FABP) Costs Two ATP

Fatty acid activation Fatty acids must be activated ATP + CoA Fatty acyl-CoA Fatty acyl-CoA must be translocated From cytoplasm to mitochondria Carnitine acyl transferase 1 and 2

Fatty acid oxidation B-oxidation Total for 16C palmitic acid? Sequential events which Convert fatty acyl-CoA to Acetyl-CoA NADH FADH Number of cycles (Number of carbon atoms/2)-1 16C FA 7 cycles Each cycle produces 1 acetyl-CoA, 1 NADH and 1 FADH Each acetyl CoA = 12 ATP Each NADH = 3 ATP Each FADH = 2 ATP Total for 16C palmitic acid?