Biochemistry

• Oxidation of fatty acids


  Process that takes place in mitochondria where the various enzymes for fatty acid oxidation are present close to the enzymes of the electron transport chain

  
• β-oxidation of fatty acids


  The most important theory of the oxidation of fatty acids

  
• Fatty acids


  • Rich sources of energy
  • Energy is released when they undergo β-oxidation

  
• β-oxidation of fatty acids


  1. Fatty acid is activated to fatty acyl CoA

  2. Carnitine carries the acyl group into the mitochondrial membrane

  3. Flavoprotein linked acyl CoA dehydrogenase removes two hydrogen atoms

  4. Enoyl CoA hydratase adds a molecule of water

  5. NAD+ oxidises β-hydroxy acyl CoA to form β-ketoacyl CoA

  6. Thiolase cleaves β-keto acyl CoA to yield acetyl CoA and fatty acyl CoA with 2 carbon atoms less

  
• Oxidation of palmitic acid (16 carbon) yields 8 molecules of acetyl CoA in 7 cycles of β-oxidation

  
• Each round of β-oxidation generates a molecule of FADH2 (1.5 ATP) and NADH+H+ (2.5 ATP)
• Total ATP produced from 7 cycles of β-oxidation of palmitic acid is 28 ATP

  
• When each acetyl CoA molecule is oxidised in the TCA cycle, 10 ATPs are generated

  
• Total ATP produced from the oxidation of palmitic acid is 106 ATP

  
• The efficiency of energy conservation by fatty acid oxidation is 33%
• Oxidation of odd chain fatty acids


  Similar to β-oxidation but with a three-carbon fragment, propionyl CoA, left behind instead of a two-carbon unit

  
• Methyl malonic aciduria


  Caused by vitamin B12 deficiency, results in the accumulation and excretion of methyl malonic acid in the urine
• Regulation of β-oxidation


  • The rate limiting step is the formation of fatty acyl-carnitine catalyzed by carnitine acyl transferase-1 (CAT-1), which is inhibited by malonyl CoA
  • In starvation, decreased malonyl CoA concentration releases the inhibition of CAT-1 and permits more acetyl CoA for oxidation

  
• Peroxisomal fatty acid oxidation


  • Peroxisomes can oxidize very long chain fatty acids (20-26 carbons) in a process similar to β-oxidation, but producing H2O2 instead of FADH2
  • Catalase in peroxisomes converts H2O2 to water and oxygen
  • Octanoyl-CoA (8 carbons) then enters mitochondria for further β-oxidation

  
• Clofibrate


  A drug that stimulates proliferation of peroxisomes and induces peroxisomal fatty acid oxidation

  
• Zellweger syndrome


  Rare inborn error of peroxisomal fatty acid oxidation, caused by a defect in the transport of enzymes into peroxisomes, leading to accumulation of long chain fatty acids

  
• ω-Oxidation


  Minor pathway for oxidation of long chain fatty acids in microsomes, occurs from both ends of the fatty acid chain, produces dicarboxylic acids

  
• Acetyl CoA is produced by aerobic glycolysis of glucose and oxidation of fatty acids via β-oxidation

  
• Sudden Infant Death Syndrome (SIDS)


  At least 10% of SIDS is due to deficiency of medium chain acyl CoA dehydrogenase, which blocks β-oxidation and energy production
• Jamaican Vomiting Sickness


  Caused by eating unripe ackee fruit containing hypoglycin A, which inhibits acyl CoA dehydrogenase and blocks fatty acid oxidation