Chemistry 332 - Spring 1996
Elements of Organic Chemistry II

Professor Carl C. Wamser

Chapter 17 - Metabolism

• catabolism - breakdown of larger molecules to smaller ones
• anabolism - buildup of larger molecules from smaller ones

• a specific example of catabolism, in which food is broken down to extract raw materials (for anabolism) and energy
• initial digestion steps are simple hydrolyses:
  • fats -> glycerol and fatty acids
  • carbohydrates -> glucose and other simple sugars
  • proteins -> amino acids
• further digestion steps convert these molecules into acetyl CoA, which enters the citric acid cycle and gets oxidized to 2 CO₂
  • the steps are oxidations and generate reduced cofactors
  • the steps are exothermic and generate ATP for energy storage
• the net result of digestion is food -> CO₂ plus reduced cofactors and ATP

• ATP is used as stored energy, useful for coupling to other reactions
• ATP hydrolysis to ADP plus phosphate releases 8 kcal/mole
• for example, glycerol -> glycerol phosphate is endothermic
  but glycerol + ATP -> glycerol phosphate + ADP is endothermic
• ATP is coupled to many other reactions (not necessarily involving phosphate) to make them more favorable

• NAD⁺ is used as a general oxidant
• reduction of NAD⁺ (by adding 2 e^- and H⁺) generates NADH
• NADH is used as a general reductant
• NAD⁺ and NADH are cofactors used with enzymes that carry out oxidation or reduction reactions

• fatty acids are broken down 2 carbons at a time, which are released as acetyl groups attached to coenzyme A (acetyl CoA)
• step 1: a conjugated double bond is created (oxidation) next to the CoA ester
• step 2: hydration of the double bond makes an alcohol
• step 3: oxidation of the alcohol makes a beta-keto ester
• step 4: a reverse Claisen condensation gives acetyl CoA plus a shorter CoA ester
• repeat steps 1 - 4 until the chain is broken down to only two carbons (acetyl CoA)

• breakdown of glucose in 10 steps to 3-carbon fragments, eventually pyruvate, which is decarboxylated to acetyl CoA (goes on to the citric acid cycle)

• overall oxidation of acetyl CoA to 2 CO₂
  (see Homework 17 answers for a step-by-step analysis of the 8 steps)

• amino acids exchange their alpha-amines for an alpha-keto group
• the alpha-keto acid is broken down like pyruvate
• the amino group goes to make glutamate

• identify the types of reactions in various steps of metabolism or other biological processes
• identify the pathways by which different types of foods are digested
• predict the products that are generated by the beta-oxidation, glycolysis, and transamination pathways
• recognize the role of ATP as an energy source
• recognize the role of NAD⁺ as an oxidant and NADH as a reductant in biological reactions