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Fat Mobilization

triacylglycerols + 3 H 2 O glycerol + 3 fatty acids. Fat Mobilization. Fat mobilization Breaks down triacylglycerols in adipose tissue. Forms fatty acids and glycerol. Hydrolyzes fatty acid initially from C1 or C3 of the fat.

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Fat Mobilization

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  1. triacylglycerols + 3 H2O glycerol + 3 fatty acids Fat Mobilization Fat mobilization • Breaks down triacylglycerols in adipose tissue. • Forms fatty acids and glycerol. • Hydrolyzes fatty acid initially from C1 or C3 of the fat. Triacylglycerol lipase inhibited by insulin and stimulated by epinephrine.

  2. Metabolism of Glycerol glycerol transported to the liver

  3. Fatty Acid Oxidation Activation Occurs in the cytoplasm Requires the input of 2 ATP equivalents

  4. CoASH carnitine carnitine CoASH Fatty Acid Oxidation Transport Across Mitochondrial Membrane

  5. First Oxidation: Double Bond Formation Fatty Acid Oxidation Addition of Water to the Double Bond

  6. Second Oxidation: Ketone Formation Fatty Acid Oxidation Cleavage Step These four reactions (oxidation, hydration, oxidation, cleavage) repeat removing two carbons at a time, producing acetyl–CoA.

  7. FADH2 FAD NAD+ acetyl–CoA NADH + H+ Fatty Acid Oxidation Cycle first oxidation H2O Cycle repeats, removing two carbons each time and making acetyl-CoA, FADH2, and NADH. hydration second oxidation cleavage

  8. (2 ATP) Fatty Acid Oxidation Summary of fatty acid oxidation for stearic acid (C18:0) Number of cycles required = 8 First oxidation x 8: 8 FADH2 = 16 ATP Second oxidation x 8: 8 NADH= 24 ATP Eight cycles yields 9 acetyl-CoA 1 acetyl-CoA = 3 NADH, 1 FADH2, 1GTP = 12 ATP Acetyl-CoA x 9= 108 ATP Initial activation cost = Net energy produced = 146 ATP

  9. sterols, steroids CO2 NADH + H+ NAD+ Other Roles of Acetyl–CoA: Precursor of Sterols, Steroids, and Ketone Bodies First condensation Second condensation HMG-CoA reductase ketone bodies

  10. Requires an acyl carrier protein (ACP). Lipogenesis: Fatty Acid Synthesis Lipogenesis Is the synthesis of fatty acids from acetyl CoA. Occurs in the cytosol. Uses reduced coenzyme NADPH.

  11. ATP ADP + Pi Fatty Acid Synthesis: Lipogenesis cytoplasm intermembrane space matrix

  12. Acetyl–CoA carboxylase Fatty Acid Synthesis Activation of Acetyl–CoA (coenzyme: biotin) Acetyl CoA carboxylase is stimulated by insulin and inhibited by glucagon and epinephrine Transfer to Acyl Carrier Protein in Fatty Acid Synthase

  13. Fatty Acid Synthesis Condensation Reaction First Reduction Reaction Reducing agent is NADPH (corresponding oxidation reaction in fatty acid oxidation pathway uses NAD+ as the oxidizing agent)

  14. Fatty Acid Synthesis Dehydration Reaction Second Reduction Reaction Reducing agent is NADPH (corresponding oxidation reaction in fatty acid oxidation pathway uses FADas the oxidizing agent) This cycle repeats using another malonyl–ACP and adding two more carbons. Fatty acid released after seven cycles.

  15. Summary of Lipogenesis

  16. Fatty Acid Length and Unsaturation In fatty acid synthesis • Shorter fatty acids undergo fewer cycles. • Longer fatty acids are produced from palmitate using special enzymes. • Unsaturated cis bonds are incorporated into a 10-carbon fatty acid that is elongated further.

  17. Regulation of Fatty Acid Synthesis In fatty acid synthesis • A high level of blood glucose and insulin stimulates glycolysis and pyruvate oxidation. • More acetyl CoA is available to form fatty acids.

  18. Oxidation: oxidationhydrationoxidationcleavage Biosynthesis: reductiondehydrationreductioncondensation Oxidation: C16:0 8 acetyl–CoA Biosynthesis: 8 acetyl–CoA C16:0 Fatty Acid Synthesis Comparison of oxidation and biosynthesis Reaction sequence: Electron acceptors and donors: Oxidation: NAD+, FAD Biosynthesis: NADPH Cellular location: Oxidation: inside mitochondrion Biosynthesis: in cytoplasm Energy produced or used for C16:0: 7 cycles = 7 NADH (21 ATP) + 7 FADH (14 ATP) – 2 ATP = 33 ATP Transport of 8 acetyl–CoA to cytoplasm: 8 ATP Synthesis of 7 malonyl–CoA: 7 ATP 7 cycles: 14 NADPH (42 ATP) Total required = 57 ATP

  19. Activated fatty acids fatty acid + CoSASH + ATP fatty acyl CoA + AMP + 2 Pi Reaction: Transport: 3 fatty acyl CoA + glycerol phosphate triacylglycerol + Pi Assembled into very-low-density lipoprotein complexes (VLDL) and these used to transport fatty acids to tissues for fuel and to adipocytes for storage. Site: liver Substrates: Synthesis of Triacylglycerols Glycerol phosphate from dihydroxyacetone phosphate

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