Lecture 17

• Fatty Acid Catabolism


  The Oxidation of Long-Chain Fatty Acids to Acetyl-CoA

  
• Fatty Acid Catabolism


  • Serves as a central energy-yielding pathway in many organisms and tissues
  • Electrons removed from fatty acids during oxidation pass through the respiratory chain + drive ATP synthesis

  
• Sources of Fatty Acid Fuels


  • Dietary fats
  • Fats stored in cells as lipid droplets
  • Fats synthesized in one organ for export to another
  • Fats obtained by autophagy

  
• Apolipoproteins


  Proteins in their lipid-free form that bind lipids to form lipoproteins

  
• Chylomicrons


  Particles consisting of triacylglycerols, cholesterol, and apolipoproteins

  
• Lipoprotein Particles


  Spherical aggregates of apolipoproteins and lipids

  
• Apolipoprotein C-ll (apoC-ll)


  Protein present in mature chylomicrons

  
• Lipoprotein lipase


  Extracellular enzyme in the capillaries of muscle and adipose tissue that hydrolyzes triacylglycerol to free fatty acids and monoacylglycerols

  
• Lipid droplets


  Organelles stores in adipocytes and steroid-synthesizing cells that contain neutral lipids

  
• Serum albumin


  Transports FFAs to target tissues, makes up 1/2 of the total serum protein
• Carnitine shuttle


  Transports long-chain fatty acids (14+ carbons) through the mitochondrial membrane

  
• Fatty acyl-CoA


  Contains a thioester linkage between the fatty acid carboxyl group and the thiol group of coenzyme A

  
• Carnitine


  Compound that transports fatty acyl-CoAs destined for mitochondrial oxidation

  
• Carnitine acyl-transferase 1, CAT1 (carnitine palmitoyltransferase 1, CPT1)


  Catalyzes a transesterification reaction to transiently attach a fatty acyl-CoA to the hydroxyl group of carnitine to form fatty acyl-carnitine

  
• Carnitine acyltransferase 2 (CAT2, CCPT2)


  Transfers the fatty acyl group from carnitine back to coenzyme A to regenerate fatty acyl-CoA and free carnitine

  
• Stages of Fatty Acid Oxidation


  • Beta-oxidation
  • Oxidation of acetyl-CoA groups to CO2 in the citric acid cycle
  • Electron transfer chain and oxidative phosphorylation

  
• Beta-oxidation of saturated fatty acids

  4 basic steps

  
• Acyl-CoA Dehydrogenase Isozymes


  VLCAD, MCAD, SCAD

  
• Acyl-CoA acetyl-transferase (thiolase)


  Catalyzes the reaction of beta-ketoacyl-CoA with free coenzyme A to yield acetyl CoA and a fatty acyl-CoA shortened by 2 carbons

  
• The four beta-oxidation steps are repeated to yield acetyl-CoA and ATP

  
• One pass through stage 1 of beta-oxidation


  Removes 1 molecule of acetyl-CoA, 2 pairs of electrons, and 4 protons (H+)

  
• Oxidation of unsaturated fatty acids


  Requires 2 additional reactions and 2 additional enzymes: enoyl-CoA isomerase (converts cis double bonds to trans) and 2,4-dienoyl-CoA reductase (reduces cis double bonds)

  
• Complete oxidation of odd-number fatty acids requires 3 extra reactions
• Propionate (CH3-CH2-COO-)


  Three-carbon compounds formed by cattle and other ruminant animals during carbohydrate fermentation
• Odd-number fatty acids are oxidized to yield acetyl-CoA and a molecule of propionyl-CoA

  
• Oxidation of Propionyl-CoA


  1. Propionyl-CoA carboxylase catalyzes the carboxylation of propionyl-CoA to form D-methylmalonyl-CoA

  2. Methylmalonyl-CoA epimerase catalyzes the epimerization of D-methylmalonyl-CoA to its L stereoisomer

  3. Methylmalonyl-CoA mutase catalyzes the intramolecular rearrangement of L-methylmalonyl-CoA to form succinyl-CoA (can enter TCA)

  
• Medium-chain acyl-CoA dehydrogenase (MCAD)


  Acyl-CoA dehydrogenase isozyme that acts on fatty acids of 4-14 carbons

  
• Thiolase


  Catalyzes the enzymatic condensation of 2 acetyl-CoA molecules to form acetoacetyl-CoA

  
• HMG-CoA synthase


  Catalyzes the condensation of acetoacetyl-CoA with acetyl-CoA to form β-hydroxy-β-methylglutaryl-CoA (HMG-CoA)

  
• HMG-CoA lyase


  Catalyzes the cleavage of HMG-CoA to free acetoacetate and acetyl-CoA

  
• Acetoacetate decarboxylase


  Catalyzes the decarboxylation of acetoacetate to acetone

  
• 1. β-hydroxybutyrate dehydrogenase


  Catalyzes the reversible reduction of acetoacetate to D-β-hydroxybutyrate

  
• Ketone bodies are used as fuels in all tissues except the liver
• Individuals with untreated diabetes have high acetone levels
• Acidosis


  Lowered blood pH
• Ketosis


  High levels of ketone bodies in the blood + urine
• Ketoacidosis


  Condition when ketosis and acidosis are combined

  
• Antigen-presenting cells (APC) present antigens to T helper cells.
• The first step to making an antibody is the activation of B cells.
• B cell receptors are on the surface of B cells, which recognize antigens.