Triglyceride Metabolism Jack Blazyk 3/1/04

Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’ Ester Glycerol backbone Fatty Acid

Triglyceride Metabolism Lipogenesis occurs mainly in liver, adipose and intestinal epithelial cells Lipolysis occurs in adipose cells Regulation via insulin and glucagon signals

Lipogenesis R-COOH R-C-S-CoA O = CoA-SH + ATP AMP + PP i Acyl-CoA Synthase Activation

Lipogenesis CH 2 — C — CH 2 lll OHOO P l DHAP Glycerol 3-P Dehydrogenase NADH + H + NAD + NADH + H + NAD + CH 2 — CH — CH 2 ll OH l O P Glycerol 3-P

Lipogenesis Glycerol CH 2 — CH — CH 2 ll OH l O P Glycerol 3-P CH 2 — CH — CH 2 ll OH l Glycerol Kinase ATP ADP Liver and kidney

Lipogenesis CH 2 — CH — CH 2 ll OH l O P Glycerol 3-P Acyl Transferases 2 Acyl-CoA 2 CoA CH 2 — CH — CH 2 ll OO C=O ll ll RR’ l O P Phosphatidic Acid

Lipogenesis CH 2 — CH — CH 2 ll OO C=O ll ll RR’ l O P Phosphatidic Acid Phosphohydrolase PiPi H2OH2O CH 2 — CH — CH 2 ll OO C=O ll ll RR’ l OH 1,2-Diacylglycerol

Lipogenesis CH 2 — CH — CH 2 ll OO C=O ll ll RR’ l OH Acyltransferase CoAAcyl-CoA 1,2-DiacylglycerolTriacylglycerol CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Lipogenesis Intestinal epithelial cells  Export via chylomicrons Liver  Export via VLDL Adipose  Storage in cytoplasm

Marks’ Basic Medical Biochemistry: A Clinical Approach (Williams & Wilkins, 1996)

Lipolysis Triacylglycerol CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’ Adipose Cells Triglyceride Lipase (Hormone-Sensitive Lipase) H20H20 CH 2 — CH — CH 2 ll OO C=O ll ll RR’ l OH 1,2-Diacylglycerol + R’’-COOH Free Fatty Acid

Lipolysis CH 2 — CH — CH 2 ll OO C=O ll ll RR’ l OH 1,2-Diacylglycerol Diglyceride Lipase H20H20 + R-COOH Free Fatty Acid 2-Monoacylglycerol CH 2 — CH — CH 2 ll OHO l C=O l R’ l OH Adipose Cells

Lipolysis Monoglyceride Lipase H20H20 2-Monoacylglycerol CH 2 — CH — CH 2 ll OHO l C=O l R’ l OH Adipose Cells + R’-COOH Free Fatty Acid CH 2 — CH — CH 2 ll OH l Glycerol FFA are transported via albumin

Regulation of Lipolysis ATP ADP PiPi H2OH2O Protein Kinase ALipase Phosphatase Triglyceride Lipase - OH Triglyceride Lipase - P ACTIVE INACTIVE Activated by insulinActivated by glucagon

Regulation of Lipolysis Activators  Glucagon  Epinephrine  ACTH  TSH  Growth hormone  Glucocorticoids  Thyroid hormones Inhibitors  Insulin  Free fatty acids

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