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).

QuickTime™ and a decompressor

are needed to see this picture.

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

QuickTime™ and a decompressor

are needed to see this picture.

Reaction 2: carnitine acyltransferases

QuickTime™ and a decompressor

are needed to see this picture.

Reactions 3-6: ß-oxidation

QuickTime™ and a decompressor

are needed to see this picture.

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).

QuickTime™ and a decompressor

are needed to see this picture.

QuickTime™ and a decompressor

are needed to see this picture.1) 2)

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).