Nucleotide pyrophosphorylases

The reaction is catalyzed by specific enzymes, usually termed204 sugar nucleotide pyrophosphorylases. The equilibrium constant is not far from unity, and addition of inorganic pyrophosphatase, an enzyme that converts inorganic pyrophosphate irreversibly into... 

The lack of absolute substrate specificity with the sugar nucleotide pyrophosphorylases allows the preparation of some analogs of the natural derivatives. The yeast pyrophosphorylase effective for synthesis of uridine 5 -(a-D-glucopyranosyl pyrophosphate) was used for synthesis of the analogous derivatives of pseudouridine228 (48) and 5-hydroxyuridine229 (49). 

Enzymatic giycosyiation using sugar nucieotide recyciing systems. Ei = pyruvate kinase, E2 = sugar nucleotide pyrophosphorylase, E3 = pyrophosphatase, E4 = sugar nucleotide synthase, E5 = myokinase, PEP = phosphoenol pyruvate, Pyr = pyruvate... 

In higher mammals, riboflavin is absorbed readily from the intestines and distributed to all tis.sues. It is the precursor in the biosynthesis of the cocnzyme.s flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). The metabolic functions of this vitamin involve these Iwocoenzymes. which participate in numerous vital oxidation-reduction proces.ses. FMN (riboflavin 5 -phosphate) is produced from the vitamin and ATP by flavokinasc catalysis. This step con be inhibited by phcnothiazincs and the tricyclic antidepressants. FAD originates from an FMN and ATP reaction that involves reversible dinucicotide formation catalyzed by flavin nucleotide pyrophosphorylase. The.se coenzymes function in combination with several enzymes as coenzyme-en-zyme complexes, often characterized as, flavoproteins. 

F2. Flaks, J. G., Erwin, M. J., and Buchaium, J. M., Biosynthesis of the purines— the synthesis of adenosine 5 phosphate and 5-amino-4-imidazolecarboxamide ribotide by a nucleotide pyrophosphorylase. J. Biol. Chem. 288, 201 (1957). 

It was not until 1953 that Goldwasser (9) and Williams and Buchanan (10) showed that purine bases could be converted to ribonucleotides by a one-step process, without the intermediate formation of ribonucleosides. The source of the ribose phosphate moiety was discovered in 1955 to be PP-ribose-P in the course of studies of adenylate synthesis by Kornberg et al. 11), and of inosinate synthesis by Korn et al. 12) extracts of yeast, beef liver, and pigeon liver were employed. The enzymes involved were at first called nucleotide pyrophosphorylases, but are now known as purine phosphoribosyltransferases. The general reaction is... 

Although nicotinamide is a vitamin, it can also be synthesized from tryptophan. Therefore, the NAD levels of the organism depend on both nicotinamide and tryptophan intake. The pathway of NAD biosynthesis starting from tryptophan is discussed in detail later. NADP is much less abundant in the cell than NAD. The biosynthesis of NADP probably involves the reaction of NAD with ATP in the presence of a nucleotide pyrophosphorylase. 

The direct synthesis of nucleotides can take place by the reaction of a purine or pyrimidine base and PRPP according to reaction (14). The reaction is catalyzed by nucleotide pyrophosphorylase. 

Two separate purine nucleotide p3rrophosphorylases have been described (61). One enzyme converts hypoxanthine, guanine (61, 68), and 6-mercaptopurine (63) to their ribotides in the presence of PRPP, while a second enzyme is active with adenine and 4-amino-5-imidazolecarboxa-mide (64). The latter enzyme has been purified from beef liver. Nucleotide pyrophosphorylase has also been purified from yeast (61). 

Davidson, J. D., Bradley, T. R., Roosa, R. A., and Law, L. W. (1962), Purine nucleotide pyrophosphorylases in 8-azaguanine-sensitive and -resistant P388 leukemias, J. Natl. Cancer Inst. 29, 789-803. 

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