LIPID METABOLISM. Recall the structures of storage lipids.
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Transcript of LIPID METABOLISM. Recall the structures of storage lipids.
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LIPID METABOLISM
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Recall the structures of storage lipids
Triacyl glycerol: energy storage (fats and oils): 38 kJ/mol (vs protein 17 kJ/mol)
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Fats and oils --storage forms of C and energy-- accumulate in lipid bodies
Other sources includediet and new synthesis.
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To be metabolized, fattyacids must be “mobilized”(released from triglycerides)
Epinephrin, glucagon,catacholamines induceactivation of lipases tomobilize lipid in fat bodies
Dietary lipid Is mobilized inthe duodenum by pancreaticlipase (C1, C3) and otherlipases (C2).
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Triglyceride ---[adipose triglyceride lipase (ATGL)]--> diglyceride —[hormone-sensitive lipase (HSL)]--> FA + glycerol Cachexia: a cancer-associated depletion of lipid in adipose tissue ("wasting disorder"): patients have increased catecholamines (lipolysis-stimulating hormones), ATGL, and HSL. Removal of ATGL or (less effectively, HSL) in mice reduces cachexia: Science 333, 163 and 233 (2011)
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triacylglyceride + 3 H2O ‡ (lipase) ‡ glycerol (5% of energy) + 3 fatty acids (95% )
Use of glycerol glycerol + ATP ‡ (glycerol kinase) ‡ glycerol-3-P + ADP
glycerol-3-P + NAD+ ‡ (glycerol-3-P dehydrogenase) ‡ DHAP ‡ glycolysis
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Use of fatty acids: ß-oxidation Overview:
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Use of fatty acids: ß-oxidation Overview: 1) activate fatty acid (add CoA) 2) import into mitochondria 3) oxidation/hydration/oxidation
4) re move acetyl-CoA
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Reaction 1: Acyl-CoA synthase
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Reaction 2: carnitine acyltransferases
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Reactions 3-6: ß-oxidation
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Energetics
palmitoyl-CoA(16 C) + CoASH + FAD + NAD+ +H2O
‡ myristyl-CoA(14 C) + acetyl-CoA + FADH2 + NADH + H+
7 times through produces: 7 NADH + H+ 17.5 ATP 7 FADH2 10.5 ATP 8 acetyl-CoA 80 ATP less activation -2 ATP 106 ATP
Note H2O generation: 1 H2O per 2 e-:
7 NADH + H+ 7 H2O 7 FADH2 7 H2O 8 acetyl-CoA 32 H2O less activation -7 H2O 39 H2O
(H2O maintains polar bears (p. 223, G&G) and camels, etc (p. 710, G&G))
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Two complications: 1) Unsaturated fatty acid have cis double bonds: these must be changed to trans by an isomerase. 2) Odd-chain fatty acids yield propionyl-CoA, which must be carboxylated to form methymalonyl-CoA, then isomerized to form succinyl-CoA (the TCA intermediate).
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Summary
Triglycerides are hydrolyzed to fatty acids plus glycerol.
Fatty acids are activated by attachment to CoA andImport into the mitochondria.
The oxidation of fatty acids involves the ß-oxidation pathway.
The oxidation of fatty acids produces a lot of ATP (and some H2O).