Lipid Metabolism Lecture PDF

Lipid Metabolism Jeff Powers, PhD. Department of Molecular Biology [email protected] Learning Objectives Describe the four major groups of plasma lipoproteins, four major lipid classes in lipoproteins, and plasma FFA - Identify lipoprotein groups (CM, VLDL, LDL, & HDL) and the...

Lipid Metabolism Jeff Powers, PhD. Department of Molecular Biology [email protected] Learning Objectives Describe the four major groups of plasma lipoproteins, four major lipid classes in lipoproteins, and plasma FFA - Identify lipoprotein groups (CM, VLDL, LDL, & HDL) and the respective lipids (TAG, CE, C, & PL) they carry - Identify lipoprotein groups and the respective major apolipoproteins (apo AI, AII, B48, B100, CII, E) - Describe the structure of a lipoprotein particle (inner core and surface layer) - Describe how fatty acids are transported in plasma (fatty acid esters and albumin bound-FFA) Discuss the major metabolic events in: - lipid digestion and absorption - lipid resynthesis, chylomicron formation, and chylomicron secretion - chylomicron degradation by lipoprotein lipase, and - fatty acid utilization by tissues Describe in brief the possible causes of steatorrhea Learning Objectives Explain how lipogenesis (triacylglycerol synthesis) occurs in the liver - Describe the main pathway for de novo fatty acid synthesis (from glucose) in the cytosol - Describe the roles of citrate synthase, malic enzyme, and acetyl-CoA carboxylase in fatty acid synthesis - Describe the roles of fatty acid synthase, acetyl-CoA, malonyl-CoA, ATP, and NADPH in fatty acid synthesis - Discuss the regulation of fatty acid synthesis by insulin, glucagon, and epinephrine Discuss adipose tissue lipolysis, plasma FFA transport, FFA uptake (by liver or muscle), fatty acid activation in the cytosol, and fatty acid transport to the mitochondria by carnitine shuttle Explain how fatty acids are oxidized in the mitochondria to generate acetyl-CoA, FADH2 and NADH - Describe the four successive reaction steps in FAO (β-oxidation of fatty acyl-CoA) leading to acetyl-CoA formation - Identify the key FAO enzymes that catalyze the formation of FADH 2 and NADH in each cycle - Explain how palmitoyl-CoA (C16) oxidation to CO2 and H2O yields a net total of 106 ATPs - Discuss the regulation of fatty acid oxidation Discuss the synthesis and utilization of ketone bodies Many figures for this lecture were created by Lakshman Segar, Ph.D., and are being included with his permission  Plasma lipoproteins in normal subjects Chylomicrons (CM; triglyceride-rich) Very low density lipoproteins(VLDL; triglyceride-rich) Low density lipoproteins (LDL; LDL-C → “bad cholesterol”) High density lipoproteins (HDL; HDL-C → “good cholesterol”) Plasma lipoprotein fractions – Isolation by density-gradient ultracentrifugation Mueller et al. Scientific Reports 12: 9138; 2022  Electron microscopy Plasma lipoprotein fractions – Particle size and density of lipoproteins d = 1.028 – 1.050 g/ml Chapman et al. J Lipid Res. 22: 339-358; 1981 RBCs: Diameter = 7-8 μm Zheng et al. Scientific Reports 11: 16086; 2021  nonpolar lipids amphi (inner core) -pathic Lipoproteins = TAG (TG) + CE + C + PL + apolipoproteins water-miscible Chylo- microns VLDL LDL HDL TG: 85%-95% TG: 50%-65% TG: 4%-8% TG: 2%-7% CE: 2%-4% CE: 16%-22% CE: 45%-50% CE: 15%-20% 45% - 55% 18% - 22% 6% - 10% 1% - 2% Protein Modified from Schaeffer and Levy N Engl J Med 312: 1300-1310; 1985  Composition of plasma lipoproteins in humans Composition Lipoprotein Source Diameter Density Protein Lipid Main Lipid Apolipoproteins (nm) (g/Ml) (%) (%) Components Chylomicrons Intestine 90-1000