LIPID METABOLISM
Recall the structures of storage lipids
Triacyl glycerol: energy storage (fats and oils): 38 kJ/mol (vs protein 17 kJ/mol)
Fats and oils --storage forms of C and energy-- accumulate in lipid bodies
Other sources includediet and new synthesis.
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)
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
Use of fatty acids: ß-oxidation Overview:
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
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))
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).