Adenine-phosphoribosyltransferase

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). 

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

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

The enzymatic conversion of many analogues of the naturally occurring purines directly to their biologically active form, the ribonucleotides, in vivo [5, 8, 10, 13, 39] underlines the importance of these enzymes to the drug action of this class of compounds. 2-Aminoadenine (2, 6-diaminopurine, I) [107], 2-fluoroadenine (II) [108], 4-aminopyrazolo [3, 4-d] pyrimidine (VIll) [109]. and 2- and 8-aza-adenine (IX and X) [ 110, 111] have all been shown to be substrates for the adenine phosphoribosyltransferase [J12, 113]. Extensive studies on the metabolism of 2-aminoadenine (I) in E. coli [114, 115], L cells [116], and mice [117] have also shown its conversion by this enzyme to the ribonucleotide. 

The reaction shown below is catalyzed by adenine phosphoribosyltransferase (APRT). 

Table 7.1.4 Concentration range of purine and pyrimidine metabolites in urine (pmol/mmol creatinine) from patients. ADA Adenosine deaminase, APRT adenine phosphoribosyltransferase, ASA adenylosuccinate lyase, DHP dihydropyrimidinase, DPD dihydropyrimidine dehydrogenase, HGPRT hypoxanthine-guanine phosphoribosyltransferase, PNP purine nucleoside phosphorylase, TP thymidine phosphorylase, UMPS uridine monophosphate synthase, / -UP fi-ureidopropionase... 

Purines that result from the normal turnover of cellular nucleic acids can be reconverted into nucleoside triphosphates and used by the body. Thus, they are "salvaged" instead of being degraded to uric acid. PRPP is the source of the ribose-phosphate, and the reactions are catalyzed by adenine phosphoribosyltransferase, and hypoxanthine-guanine phosphoribosyltransferase (HPRT). 

Adenine phosphoribosyltransferase catalyzes the conversion of adenine to AMP in many tissues, by a reaction similar to that of hypoxanthine-guanine phosphoribosyltransferase, but is quite distinct from the latter. It plays a minor role in purine salvage since adenine is not a significant product of purine nucleotide catabolism (see below). The function of this enzyme seems to be to scavenge small amounts of adenine that are produced during intestinal digestion of nucleic acids or in the metabolism of 5 -deoxy-5 -methylthioadenosine, a product of polyamine synthesis. 

Metabolic pathways for the conversion of adenine. Adenine is normally salvaged by conversion to AMP by adenine phosphoribosyltransferase (APRT). In the absence of APRT, adenine is oxidized to the highly insoluble product 2,8-dihydroxyadenine by xanthine oxidase. 

Purine salvage pathway The synthesis of purine nucleotides by the condensation of the purine bases with phosphoribosyl pyrophosphate. As the name suggests, it is a way in which purine bases can be recycled back to nucleotides. The purine salvage pathway consists of two enzymes, HGPRT and adenine phosphoribosyltransferase (APRT). 

Adenine phosphoribosyltransferase (ARPT) catalyzes the transfer of adenine to PRPP, thus forming AMP ... 

Walter, R. D., and Konigk, E. (1974b). Hypoxanthine-guaninephosphoribosyltransferaseand adenine phosphoribosyltransferase from Plasmodium chabaudi, purification and properties. Tropenmed. Parasitol. 25, 227-235. 

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