17.8 Amino Acid Catabolism Amino acids from degraded proteins or from diet can be used for the biosynthesis of new proteins During starvation proteins are degraded to amino acids to support glucose formation First step is often removal of the  -amino group Carbon chains are altered for entry into central pathways of carbon metabolism

17.9 The Urea Cycle Converts Ammonia into Urea Waste nitrogen must be removed (ammonia is toxic to plants and animals) Terrestrial vertebrates synthesize urea (excreted by the kidneys) Birds, reptiles synthesize uric acid

Fig Synthesis of carbamoyl phosphate (removal of NH 3 ) Catalyzed by carbamoyl phosphate synthetase I (CPS I)

Fig (cont) (from previous slide)

Carbamoyl phosphate synthetase is allosterically activated by N- acetylglutamate KEY REGULATION STEP in the pathway!

A. The Reactions of the Urea Cycle Urea cycle (Fig next two slides) Rxn 1 (mitochondria), Rxns 2,3,4 (cytosol) Two transport proteins are required: Citrulline-ornithine exchanger Glutamate-aspartate exchanger Overall reaction for urea synthesis is: NH 3 + HCO Aspartate + 3 ATP Urea + Fumarate + 2 ADP + 2 P i + AMP + PP i

B. Ancillary Reactions of the Urea Cycle Supply of nitrogen for the urea cycle can be balanced by supply of NH 3 and amino acids Glutamate dehydrogenase and aspartate transaminase catalyze near equilibrium reactions Flux through these enzymes depends upon relative amounts of ammonia and amino acids Two cases (next slides): (a) NH 3 in excess, (b) aspartate in excess

Fig (a) Balancing the supply of nitrogen for the urea cycle

Fig (b)

17.10 Catabolism of the Carbon Chains of Amino Acids After removal of amino groups, carbon chains of the 20 amino acids can be degraded Degradation products: Citric acid cycle intermediates Pyruvate Acetyl CoA or acetoacetate

Glucogenic vs ketogenic amino acids Glucogenic amino acids can supply gluconeogenesis pathway via pyruvate or citric acid cycle intermediates Ketogenic amino acids can contribute to synthesis of fatty acids or ketone bodies Some amino acids are both glucogenic and ketogenic