chapter 17 - amino acid metabolism metabolism of the 20 common amino acids is considered from the...
TRANSCRIPT
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
Nitrogenase
• 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
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 of -ketoglutarate by glutamate dehydrogenase 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 glutamine synthetase
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
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: -ketoglutarate
17.3 Transamination Reactions
• Transfer of an amino group from an -amino acid to an -keto acid
• In amino acid biosynthesis, the amino group of glutamate is transferred to various -keto acids generating -amino acids
• In amino acid catabolism, transamination reactions generate glutamate or aspartate