Phosphoribosyltransferase

JW Pitera, NR Munagala, CC Wang, PA Kollman. Understanding substrate specificity m human and parasite phosphoribosyltransferases through calculation and experiment. Biochemistry 38 10298-10306, 1999. 

Anthranilatesynthase-phosphoribosyltransferase Salmonella typhimurium, 6,582 Anthranilic acid in gravimetry, 1,530 metal complexes, 2, 795 synthesis... 

While mammahan cells reutilize few free pyrimidines, salvage reactions convert the ribonucleosides uridine and cytidine and the deoxyribonucleosides thymidine and deoxycytidine to their respective nucleotides. ATP-dependent phosphoryltransferases (kinases) catalyze the phosphorylation of the nucleoside diphosphates 2 "-de-oxycytidine, 2 -deoxyguanosine, and 2 -deoxyadenosine to their corresponding nucleoside triphosphates. In addition, orotate phosphoribosyltransferase (reaction 5, Figure 34-7), an enzyme of pyrimidine nucleotide synthesis, salvages orotic acid by converting it to orotidine monophosphate (OMP). 

Orotate phosphoribosyltransferase (reaction 5, Figure 34-7) converts the drug allopurinol (Figure 33-12) to... 

The orotic aciduria that accompanies Reye s syndrome probably is a consequence of the inabifity of severely damaged mitochondria to utifize carbamoyl phosphate, which then becomes available for cytosofic overproduction of orotic acid. Type I orotic aciduria reflects a deficiency of both orotate phosphoribosyltransferase and orotidylate decarboxylase (reactions 5 and 6, Figure 34—7) the rarer type II orotic aciduria is due to a deficiency only of orotidylate decarboxylase (reaction 6, Figure 34-7). 

Many yeasts are inhibited by 5-fluorocytosine and a block in the synthesis of 5-fluorouridylic acid by loss of cytosine deaminase or of nracil phosphoribosyltransferase is sufficient to cause resistance. Mntational loss of pyrimidine salvage enzymes has been frequently observed. 

Adenine phosphoribosyltransferase (APRT) deficiency is an inherited disorder of purine metabolism and is inherited in an autosomal recessive manner (K18, V7). This enzyme deficiency results in an inability to salvage the purine base adenine, which is oxidized via the 8-hydroxy intermediate by xanthine oxidase to 2,8-di-hydroxyadenine (2,8-DHA). This produces crystalluria and the possible formation of kidney stones due to the excretion of excessive amounts of this insoluble purine. Type I, with virtually undetectable enzyme activity, found predominantly in Caucasians, is found in homozygotes or compound heterozygotes for null alleles. Type II, with significant APRT activity, found only in Japan, is related to a missense mu-... 

H5. Hidaka, Y., Tarle, S. A., Fujimori, S Kamatani, N Kelley, W. N., and Palella, T. D., Human adenine phosphoribosyltransferase deficiency Demonstration of a single mutant allele common to the Japanese. J. Clin. Invest. 81,945-950 (1988). 

K2. Kamatani, N., Hakoda, M., Otsuka, S., Yoshikawa, H., and Kashiwazaki, S., Only three mutations account for almost all defective alleles causing adenine phosphoribosyltransferase deficiency in Japanese patients. J. Clin. Invest. 90, 130-135 (1992). 

P5. Patel, P. I., Caskey, C. T., and Chinault, C. A., Fine structure of the human hypoxanthine guanine phosphoribosyltransferase gene. Mol. Cell. Biol. 6,393-403 (1986),... 

Marcus, S.L., and Balbinder, E. (1972) Use of affinity matrices in determining steric requirements for substrate binding Binding of anthranilate 5-phosphoribosyl-pyrophosphate phosphoribosyltransferase from Salmonella typhimurium to Sepharose-anthranilate derivatives. Anal. Biochem. 48, 448-459. 

The free bases of the purines can be salvaged to spare de novo synthesis. The only hard thing is remembering what the names stand for. HGPRTase is hypoxanthine-guanine phosphoribosyltransferase, and it makes both IMP and GMP. A separate enzyme exists for the salvage of adenine. The salvage pathways are included in Fig. 19-1. 

Puig, J. G., Torres, R. J., Mateos, E A. et al. The spectrum of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Clinical experience based on 22 patients from 18 Spanish families. Medicine (Baltimore) 80 102-112,2001. 

Smith, D. W. and Friedmann, T. Characterization of the dopamine defect in primary cultures of dopaminergic neurons from hypoxanthine phosphoribosyltransferase knockout mice. Mol. Ther. 1 486-491,2000. 

APRT adenine phosphoribosyltransferase CGRP calcitonin gene-related peptide... 

EphR erythropoietin-producing hepatocellular receptor HGPRT hypoxanthine-guanine phosphoribosyltransferase... 

HPRT hypoxanthine phosphoribosyltransferase acidosis, and stroke-like episodes... 

II.4f LOC -9kbF 8B3.3 0 LOC621377, similar to Adenine phosphoribosyltransferase (APRT) 4... 

Deficiencies of adenosine deaminase and hypoxanthine-guanine phosphoribosyltransferase or a low activity of thymi-dylate synthase are responsible for clinical disorders. 

Lesch-Nyhan syndrome A deficiency of hypoxanthine-guanine phosphoribosyltransferase results in accumulation of purine bases (Chapter 10). This causes a marked increase in the plasma level of uric acid, and hence can give rise to gout, but it also causes a severe neurological disorder, known as Lesch-Nyhan syndrome, the symptoms of which include... 

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