Glutamine phosphoribosylpyrophosphate

Glutamine 5-phosphoribosyl-l-pyrophosphate amidotransferase, 38 310-311 Glutamine phosphoribosylpyrophosphate amidotransferase, ground spin state variability, 38 99-100 Glutathion... 

Step 1, in which phosphoribosylamine is formed, is catalyzed by glutamine phosphoribosylpyrophosphate ami-... 

Holmes, E.W., Wyngaarden, J.B., and Kelley, W.N. Human glutamine phosphoribosylpyrophosphate amidotransferase Two molecular forms interconvertible by purine ribonucleotides and phosphoribosylpyrophosphate. J. Biol. Chem., 248 6035,1973. 

Wyngaarden, J. B. 1972. Glutamine phosphoribosylpyrophosphate amidotransferase. In Current Topics in Cellular Regulation. 

FIGURE 15 Examples o a + proteins, (a) Ubiquitin, (b) Papain consists of one alpha-helix and four strands of antiparallel beta-sheet, (c) ribonuclease A, and (d) N-terminal domain of E. co//glutamine phosphoribosylpyrophosphate (Prpp) amidotransferase that contains a four structural layers appa. 

HUMAN GLUTAMINE PHOSPHORIBOSYLPYROPHOSPHATE (PP-RIBOSE-P) AMIDOTRANS-FERASE KINETIC, REGULATION AND CONFIGURATIONAL CHANGES... 

Figure 1 depicts the important steps in purine biosynthesis de novo. The first reaction which is unique to this pathway is catalyzed by the enzyme glutamine phosphoribosylpyrophosphate amidotransferase. The substrates for this reaction are phosphoribosylpyrophosphate, or PP-ribose-P, glutamine and water and the products are phosphoribosylamine, glutamate and inorganic pyrophosphate. Data obtained from the study of many species indicate that this reaction catalyzed by amidotransferase is the rate limiting step in purine biosynthesis. Phosphoribosylamine is then converted by a series of enzymatic reactions to the parent purine ribonucleotide IMP, and IMP is subsequently converted to GMP and AI IP. 

Rowe, P.B., Coleman, M.D. and Wyngaarden, J.B. 1970. Glutamine phosphoribosylpyrophosphate amidotransferase. Catalytic and conformational heterogeneity of the pigeon liver enzyme. Biochem. 1498-1505. 

When injected, azathioprine (Imuran) is rapidly converted to 6-mercaptopurine. The half-life of azathioprine after intravenous injection is 10 to 20 min, and that of 6-mercaptopurine is somewhat longer. The cytotoxic activity of these thiopurines is due to the conversion of mercaptopurine to 6-thiouric acid, a noncarcinostatic metabolite. This action is thought to block the excess synthesis of inosinic acid from its precursors, glutamine and phosphoribosylpyrophosphate. In addition, unlike cyclophosphamide, azathioprine is a potent anti-inflammatory substance that can cause a reduction in the number of monocytes and neutrophils at inflammatory sites. Antibody responses are also inhibited by azathioprine. Studies in humans have shown that azathioprine decreases the y-globulin and antibody levels, thus influencing IgG rather than IgM production. This makes azathioprine an effective immunosuppressant in the early phases of immune responses. It is less effective or completely ineffective in altering either the effector phase or already established reactivities. 

Further purification of the second fraction showed that one of its enzymic components reacted PRPP with glutamine to yield another unidentified ribose compound and equivalent amounts of glutamic acid and pyrophosphate (86, 97). 5-Phosphoribosylamine (PRA) was believed to be the unknown compoimd, since synthetic PRA replaced the biosynthetically-formed ribose derivative in the subsequent reaction with glycine and ATP to form GAR, adenosine diphosphate (ADP), and inorganic P (98). The enzyme that catalyzed the formation of PRA from glutamine and PRPP has been purified from the soluble proteins of pigeon liver and named 5-phosphoribosylpyrophosphate amidotransferase (86). Unfortunately, it was not possible to isolate the natural product of the reaction because of extreme lability of the compound. 

Nagy, M. 1970. Regulation of the biosynthesis of purine nucleotides in Schizosaccharomyces pombe. I. Properties of the phosphoribosylpyrophosphate glutamine amidotransferase of the wild strain and of a mutant desensitized towards feedback modifers. Biochim. Biophys. Acta. 198 471-481. 

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