Glutamine enzyme-catalyzed reactions

A three-substrate, three-product enzyme-catalyzed reaction scheme in which the three substrates (A, B, and C) and three products (P, Q, and R) can bind to and be released in any order. A number of enzymes have been reported to have this mechanism for example, adenylosuccinate synthetase , glutamate dehydrogenase, glutamine synthetase , formyltetrahydrofolate synthetase, and tubulin tyrosine ligase . See Multisubstrate Mechanisms... 

This enzyme catalyzes the ATP-dependent reaction of glutamyl-tRNA° " with glutamine to produce glutami-nyl-tRNA° ", ADP, orthophosphate, and glutamate. 

The first two steps in the biosynthesis of tryptophan in Salmonella typhimurium involve the enzyme complex anthranilate synthase-phosphoribosyltransferase, which is a tetramer having two subunits of each enzyme. The anthranilate synthase catalyzes reaction (7) and the phos-phoribosyltransferase catalyzes two reactions the N-terminal portion cleaves glutamine to glutamate giving NH3 for the anthranilate synthase, while the C-terminal portion catalyzes reaction (8).3,1,312 All these reactions require M2+ cations. Orotate phosphoribosyltransferase binds four Mn2+ ions in a cooperative fashion kinetic data have been interpreted in a scheme where both metal-free and metal-containing enzyme catalyze the reaction.313... 

Glutamine synthetase catalyzes the incorporation of ammonia into glutamine, deriving energy from the hydrolysis of ATP (Fig. 3b). This enzyme is named a synthetase, rather than a synthase, because the reaction couples bond formation with the hydrolysis of ATP. In contrast, a synthase does not require ATP. 

AG° for this reaction is -16.3 kJ mol 1, and hence it is thermodynamically favorable. The enzyme glutamine synthetase catalyzes this reaction in animal cells (Chap. 15). 

Dihydroorotate dehydrogenase, the enzyme catalyzing the dehydrogenation of dihydroorotate to orotate (reaction 4 of the pathway Fig. 15-15), is located on the outer side of the inner mitochondrial membrane. This enzyme has FAD as a prosthetic group and in mammals electrons are passed to ubiquinone. The de novo pyrimidine pathway is thus compartmentalized dihydroorotate synthesized by trifunctional DHO synthetase in the cytosol must pass across the outer mitochondrial membrane to be oxidized to orotate, which in turn passes back to the cytosol to be a substrate for bifunctional UMP synthase. Mammalian cells contain two carbamoyl phosphate synthetases the glutamine-dependent enzyme (CPSase II) which is part of CAD, and an ammonia-dependent enzyme (CPSase /) which is found in the mitochondrial matrix, and which is used for urea and arginine biosynthesis. Under certain conditions (e.g., hyperammonemia), carbamoyl phosphate synthesized in the matrix by CPSase I may enter pyrimidine biosynthesis in the cytosol. 

Figure 24.28. A Higher Level in the Regulatory Cascade of Glutamine Synthetase. and Pq the regulatory proteins that control the specificity of adenylyl transferase, are interconvertible. P is converted into Pq by uridylylation, which is reversed by hydrolysis. The enzymes catalyzing these reactions are regulated by the concentrations of metabolic intermediates.

The thousands of enzyme-catalyzed chemical reactions in living cells are organized into a series of biochemical (or metabolic) pathways. Each pathway consists of a sequence of catalytic steps. The product of the first reaction becomes the substrate of the next and so on. The number of reactions varies from one pathway to another. For example, animals form glutamine from a-ketoglutarate in a pathway that has two sequential steps, whereas the synthesis of tryptophan by Escherichia coli requires 13 steps. Frequently, biochemical pathways have branch points. For example, chorismate, a metabolic intermediate in tryptophan biosynthesis, is also a precursor of phenylalanine and tyrosine. 

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