CHM4116 (Finals) Lipid Metabolism

• Lipids


  Represent an efficient way of storing chemical energy
• Metabolic oxidation of lipids


  Releases large quantities of energy through the production of acetyl-CoA, NADH, and FADH2

  
• Acetyl-CoA produces 10 ATPs
• Acetyl-CoA


  • 3 NADH x 2.5
  • 1 FADH2 x 1.5
  • 1 ATP

  
• Catabolism of Lipids


  1. Oxidation of fatty acids is the chief source of energy

  2. Triacylglycerol is the main storage form of chemical energy

  3. Phosphoacylglycerol is a key component of biological membranes

  
• Triacylglycerols and Phosphoacylglycerols have fatty acids as part of their covalently bonded structures

  
• Lipases


  Hydrolyze lipids
• Phospholipases


  Hydrolyze phospholipids
• There is a higher energy yield in the oxidation of fatty acids than in the oxidation of carbohydrates, even if the number of carbons is the same

  
• Qualitative explanation


  Carbon atoms in fatty acids are more reduced than the carbon atoms in glucose, so more NADH, FADH, GTP will be produced, thus higher energy will be yielded

  
• Quantitative explanation: 18C carbohydrate (glucose) yields 90 ATPs, while 18C fatty acid (stearic) yields 120 ATPs
• Fatty Acid Activation


  1. Activation in lipid metabolism: Thioester bond is formed between the carboxyl group of the fatty acids and the thiol group of CoA-SH

  2. Acyl-CoA synthetase catalyzes formation of the ester bond and requires ATP

  3. Esterification takes place in cytosol, but the rest of the reactions occur in the mitochondrial matrix

  4. Acyl-CoA can cross the outer mitochondrial membrane but not the inner membrane

  5. Acyl group is transferred to carnitine, carried across the inner mitochondrial membrane, and transferred to mitochondrial CoA-SH by transesterification reactions

  
• Carnitine


  Molecule used in fatty acid metabolism to shuttle acyl groups across the inner mitochondrial membrane

  
• Carnitine acyltransferase (CPT-I)


  Transfers a fatty acyl group to carnitine, found on the cytosol side of the inner mitochondrial membrane with a specificity for acyl groups between 14 and 18 carbons long

  
• Carnitine palmitoyltransferase (CPT-II)


  Transfers the acyl group from carnitine to mitochondrial CoA-SH, found in the mitochondrial matrix

  
• β-Oxidation


  1. Repeated series of reactions that cleaves two-carbon units from the carboxyl end of a fatty acid

  2. Requires four reactions: oxidation, hydration, oxidation, and cleavage

  
• Stearic acid (18 carbons) gives rise to 9 acetyl CoA after 8 cycles of β-oxidation

  
• NADH = 8, FADH = 8 from β-oxidation of stearic acid
• Total ATP from oxidation of stearic acid is 120
• Rounds of β-oxidation


  (n/2) - 1
• NADH and FADH


  Rounds of β-oxidation
• Total ATP = Acetyl CoA x 10 + NADH x 2.5 + FADH x 1.5 - 2
• Oxidation of monounsaturated fatty acids (e.g. oleic acid) yields less ATP than saturated fatty acids (e.g. stearic acid) due to fewer FADH2 produced

  
• Oxidation of Polyunsaturated Fatty Acids


  Requires cis-trans isomerization to convert to acetyl-CoA

  
• Ketone Bodies


  • Acetone, β-hydroxybutyrate, and acetoacetate
  • Formed when the amount of acetyl-CoA produced is excessive compared to the amount of oxaloacetate available

  
• Starvation and diabetes can lead to excessive production of ketone bodies
• Acetoacetate can be used as a fuel in most tissues and organs
• Rounds


  (n/2) - 1
• FADH


  Rounds - no. of double bonds
• Total ATP


  1. Acetyl CoA x 10

  2. NADH x 2.5

  3. FADH x 1.5

  4. - 2 ATP
• More energy will be yielded from SATURATED FATTY ACIDS than unsaturated fatty acids
• The number of FADH2 will decrease in unsaturated fatty acids; thus, less ATP will be generated

  
• Ketone Bodies are formed when the amount of acetyl-CoA produced is excessive when compared to the amount of oxaloacetate available to react with it

  
• Starvation causes an organism to break down fats for energy, leading to the production of large amount of acetyl-CoA by β-oxidation
• In diabetic patients, the cause of imbalance is inadequate intake of carbohydrates
• Ketone bodies are formed principally in liver mitochondria
• Ketone bodies


  • Acetone
  • β-hydroxybutyrate
  • acetoacetate
• Fatty acid biosynthesis is anabolic and not the exact reversal of β-oxidation reactions

  
• Fatty acid biosynthesis occurs at the Cytosol

  
• Acetyl-CoA


  Can be formed by β-oxidation of fatty acids or decarboxylation of pyruvate