23. Glutamine Synthetase of Mammals

Abstract

This chapter discusses the physical, chemical, and catalytic properties of glutamine synthetase of mammals. Glutamine is present in virtually all mammalian tissues in both the free-state and as a constituent of proteins. Some tissues such as brain, liver, and heart contain substantial concentrations of free glutamine, and glutamine is the most abundant amino acid constituent of mammalian blood. The wide distribution of glutamine in mammalian tissues and body fluids is consistent with its significant metabolic role. Thus, glutamine is not only required as a building block of most proteins, but it also provides a source of nitrogen for a number of biosynthetic pathways. The utilization of the amide nitrogen atom of glutamine is catalyzed by a group of enzymes known as the “glutamine amide transferases.” The reactions catalyzed by these enzymes lead to the synthesis of such important biological compounds as the pyridine nucleotide coenzymes, purines, pyrimidines, and glucosamine. The amide nitrogen atom of glutamine is directly utilized for synthesis of the amide nitrogen atoms of DPN and asparagine, nitrogen atoms 3 and 9 of the purine ring, and the amino groups of guanine and cytidine. Glutamine amide nitrogen is the precursor of the nitrogen atom of carbamyl phosphate in many tissues. The synthesis of glutamine from glutamate and ammonia by glutamine synthetases represents one of several quantitatively significant enzymic mechanisms for the utilization of ammonia.