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The Fate of Ammonium
Three major reactions in all cells
• Carbamoyl-phosphate synthetase I
– two ATP required - one to activate bicarb,
one to phosphorylate carbamate
• Glutamate dehydrogenase
– reductive amination of alpha-ketoglutarate
to form glutamate
• Glutamine synthetase
– ATP-dependent amidation of gammacarboxyl of glutamate to glutamine
Glutamine Synthetase
A Case Study in Regulation
• GS in E. coli is regulated in three ways:
– Feedback inhibition
– Covalent modification (interconverts
between inactive and active forms)
– Regulation of gene expression and protein
synthesis control the amount of GS in cells
– But no such regulation occurs in eukaryotic
versions of GS
Allosteric Regulation
of Glutamine Synthetase
• Nine different feedback inhibitors: Gly,
Ala, Ser, His, Trp, CTP, AMP,
carbamoyl-P and glucosamine-6-P
• Gly, Ala, Ser are indicator of amino acid
metabolism in cells
• Other six are end products of a
biochemical pathway
• This effectively controls glutamine’s
contributions to metabolism
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