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LIPID METABOLISM

LIPID METABOLISM. SOURCES OF TRIACYLGLYCEROLS. Diet De novo biosynthesis Storage depots in adipocytes. DIGESTION, ABSORPTION, and TRANSPORTATION. Major problem: insolubility in aqueous environment Solution: bile salts and formation of lipoproteins. BILE SALTS.

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LIPID METABOLISM

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  1. LIPID METABOLISM

  2. SOURCES OF TRIACYLGLYCEROLS • Diet • De novo biosynthesis • Storage depots in adipocytes

  3. DIGESTION, ABSORPTION, and TRANSPORTATION • Major problem: insolubility in aqueous environment • Solution: bile salts and formation of lipoproteins

  4. BILE SALTS • Detergent substances synthesized in the liver and stored in the gallbladder • Essential in lipid digestion • Made up of a bile acid and an associated cation. • Bile acids are derived from cholesterol • Bile salts are amphipatic

  5. LIPOPROTEINS • Several types classified according to their density • Lipoproteins in each class contain characteristic apoproteins and have distinct lipid composition APOPROTEIN-a protein w/o its characteristic prosthetic group • Higher lipid abundance, lower density

  6. Together, the lipoproteins help maintain in emulsified form some 500 mg of total lipid per 100 ml of human blood in the post absorptive state

  7. TRANSPORT AND UTILIZATION • CHYLOMICRONS – from intestines to peripheral tissues (heart, muscle, adipose) • VLDL – for TAGs synthesized in the liver • IDL – derived from VLDL • LDL – principal form in which cholesterol is transported to tissues • HDL – returns excess cholesterol from tissues to liver for metabolism or excretion

  8. PA NCREATIC LIPASE • an unusual calcium-requiring enzyme that catalyzes a reaction at an oil-water interface • Acts via an active site serine and an acyl-enzyme intermediate Products of fat digestion comprise a mixture of glycerol, free fatty acids, monoacylglycerol, and diacylglycerol Resynthesis of TAGs occurs in the ER and Golgi complex of mucosal cells TAGs emerge into the lymph system complexed with protein to form the lipoproteins called CHYLOMICRONS

  9. MOBILIZATION OF FAT • The capacity to store fat is unlimited but the release of fat from storage depots is controlled hormonally • The first step of mobilization is the hydrolysis of TAG into glycerol and FFA • This step is controlled by a cascade involving cAMP • ACTIVATORS: epinephrine (stress) or glucagon (fasting)

  10. MOBILIZATION OF FAT • Hormone-receptor interaction activates adenylate cyclase which in turn activates cAMP. • cAMP activates protein kinase A phosphorylates triacylglycerol lipase (hormone-sensitive lipase) which catalyzes the hydrolytic release of FA from C1 or C3 • The TAG hydrolysis products exit the adipocyte by passive diffusion, goes to the blood plasma, and bind to albumin • Each molecule of albumin can bind up to 10 molecules of FFA

  11. FATTY ACID ACTIVATION and TRANSPORT • Fatty acids are present in the cytosol • FA oxidation occurs in the inner mitochondria • Fatty acyl-CoA is the active form • The reaction is catalyzed by fatty acyl CoA synthetase which are length-specific • Activation is a two-step process (outer mitochondria)

  12. BETA-OXIDATION PATHWAY • Each series of steps acetyl CoA is produced • 4 steps per cycle • The acetyl CoA produced will enter the Kreb’s cycle, where it is oxidized into CO2

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