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Chapter 17 - Amino Acid Metabolism. Metabolism of the 20 common amino acids is considered from the origins and fates of their: (1) Nitrogen atoms (2) Carbon skeletons For mammals: Essential amino acids must be obtained from diet Nonessential amino acids - can be synthesized.
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Chapter 17 - Amino Acid Metabolism • Metabolism of the 20 common amino acids is considered from the origins and fates of their: (1) Nitrogen atoms (2) Carbon skeletons • For mammals: Essential amino acids must be obtained from dietNonessential amino acids - can be synthesized
17.1 The Nitrogen Cycle and Nitrogen Fixation • Nitrogen is needed for amino acids, nucleotides • Atmospheric N2 is the ultimate source of biological nitrogen • Nitrogen fixation: a few bacteria possess nitrogenase which can reduce N2 to ammonia • Nitrogen is recycled in nature through the nitrogen cycle
An enzyme present in Rhizobium bacteria that live in root nodules of leguminous plants • Some free-living soil and aquatic bacteria also possess nitrogenase • Nitrogenase reaction: • N2 + 8 H+ + 8 e- + 16 ATP • 2 NH3 + H2 + 16 ADP + 16 Pi Nitrogenase
17.2 Assimilation of Ammonia • Ammonia generated from N2 is assimilated into low molecular weight metabolites such as glutamate or glutamine • At pH 7 ammonium ion predominates (NH4+) • At enzyme reactive centers unprotonated NH3 is the nucleophilic reactive species
A. Ammonia Is Incorporated into Glutamate • Reductive amination ofa-ketoglutarate by glutamatedehydrogenase occurs in plants, animals and microorganisms • In mammals & plants, located in mitochondria.
B. Glutamine Is a Nitrogen Carrier in Many Biosynthetic Reactions • A second important route in assimilation of ammonia is via glutaminesynthetase
Glutamate synthase transfers a nitrogen to a-ketoglutarate Prokaryotes & plants
Fig 17.3 Alternate amino acid production in prokaryotes Especially used if [NH3] is low. Km of Gln synthetase lower than Km of Glu dehydrogenase.
Box 17.1 How some enzymes transfer ammonia from glutamine • CP synthetase has 3 active sites connected by a tunnel running through the interior • Protects intermediates from being degraded by water
Carbamoyl phosphate synthase backbone structure • Tunnel connecting active sites (blue wire)
C. Regulation of Glutamine Synthetase in E. coli • Glutamine synthetase (GS) plays a critical role in nitrogen metabolism • E. coli enzyme regulated by:(1) Cumulative feedback inhibition (9 allosteric inhibitors with additive effects)(2) Covalent modification(3) Regulation of enzyme synthesis
Regulation of mammalian GS • Regulation not as extensive as in microorganisms • No covalent regulation • Allosteric inhibitors: glycine, serine, alanine, and carbamoyl phosphate • Allosteric activator:a-ketoglutarate
17.3 Transamination Reactions • Transfer of an amino group from ana-aminoacid to ana-keto acid • In amino acid biosynthesis, the amino group of glutamate is transferred to variousa-keto acids generatinga-amino acids • In amino acid catabolism, transamination reactions generate glutamate or aspartate
Fig 17.7 • Ping-pong kinetics of aspartate transaminase (next slide)
Fig 17.7 (cont) (from previous slide)