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Lipid metabolism

Lipid metabolism. Roles of lipids. Largest energy store Insulation Structural components Membranes Hormones Carrier Fat-soluble vitamins. Types of lipids. Simple lipids Mostly triglycerides Principal storage form >95% of body fat Mostly in adipose cells

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Lipid metabolism

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  1. Lipid metabolism

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

  3. Types of lipids • Simple lipids • 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

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

  5. 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

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

  7. Lipoproteins • LDL and VLDL: • 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Triglyceride synthesis Fatty acyl CoA

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

  14. 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

  15. Lipid mobilization • Hormone sensitive lipase • 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

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

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

  18. 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

  19. 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

  20. Fatty acid oxidation • B-oxidation • 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?

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