Purine metabolism, enzymes

Enzymes in general vary widely in their substrate specificity, and this wide variation is found in the purine-metabolizing enzymes, as will be seen from the... 

Singhal, D., Morgan, M. E. and Anderson, B. D. (1997) Role of brain tissue localized purine metabolizing enzymes in the central nervous system delivery of anti-HIV agents 2 -P-fluoro-2, 3 -dideoxyinosine and 2 -P-fluoro-2, 3 -dideoxy-adenosine in rats. Pharmaceutical Res., 14, 786-792. 

Johnson, M. D. and Anderson, B. D. (1996) Localization of purine metabolizing enzymes in bovine brain microvessel endothelial cells an enzymic blood-brain barrier for dideoxynucleo-sides Pharm. Res., 13, 1881-1886. 

Yamada, K. A., and Sherman, I. W. (1981b). Purine metabolizing enzymes of Plasmodium lophurae and its host cell, the duckling (Anas domesticus) erythrocyte. Mol. Biochem. Parasitol. 2,349-358. 

Hassan, H. F. and Coombs, G. H. (1985) Leishmania mexicana purine-metabolizing enzymes of amastigotes and promastigotes. Exp. Parasitol. 59 139-150. 

Nolan, L. L. and Kidder, G. W. (1980) Inhibition of growth and purine-metabolizing enzymes of trypanosomid flagellates by Ng-methyladenine. Antimicrob. Agents Chemother. 17 567-571. 

Schneider, W.C., Hogeboom, G.H. Intracellular distribution of enzymes IX Certain purine-metabolizing enzymes. J. biol. Chem. 195, 161-166(1952)... 

J. Mejer and P. Nygaard, Ageing and activities of purine metabolizing enzymes in leukocytes. In Inborn Errors of Immunity and Phagocytosis (F. Guttler, J. W. T. Seakins and R. A. Harkness, Eds.) p. 181 MTP Press. 

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-... 

Uric acid is one of the principal products of purine metabolism in man 12 13). However, in many other organisms further oxidative degradation of the purine molecule occurs. One of the most important enzymes involved in uric acid oxidation is uricase, which has been studied to some extent in vitro. 

Purine metabolism in some mammals is characterized by a further oxidation of uric acid to al-lantoin by the enzyme urate oxidase. Allantoin is significantly more water soluble than uric acid and is also freely excreted via the renal route. 

Mutations in the gene for adenylosuccinate lyase (ASL), inherited as an autosomal recessive disorder in purine metabolism, are associated with severe mental retardation and autistic behavior, but apparently not self-mutilation [10, 11]. This enzyme catalyzes two distinct reactions in the de novo biosynthesis of purines the cleavages of adenylosuccinate (S-Ado) and succinylaminoimidazole carboxamide ribotide (SAICAR), both of which accumulate in plasma, urine and cerebrospinal fluid of affected individuals [12]. Measurements of these metabolites in urine... 

Adenosine deaminase (ADA) was the first therapeutic enzyme coupled to PEG with the aim of reducing clearance and thereby overcoming the short half-life of ADA. Patients deficient in ADA are unable to regulate purine metabolism. As a result purine metabolites (e.g., adenosine monophosphate) accumulate to cytotoxic levels in B-lymphocytes and lead to severe B-cell depletion that presents clinically as severe combined immunodeficiency syndrome (SCIDS). While intramuscular injection of unmodified ADA provides some relief, antibodies develop rapidly against the protein and prevent it from being useful as replacement therapy. Even in the absence of antibodies, unmodified ADA s plasma half-life is only a few minutes. 

Gout is a metabolic disease characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate in joints and cartilage. Uric acid renal calculi, tophi, and interstitial nephritis may also occur. Gout is usually associated with hyperuricemia, high serum levels of uric acid, a poorly soluble substance that is the major end product of purine metabolism. In most mammals, uricase converts uric acid to the more soluble allantoin this enzyme is absent in humans. While clinical gouty episodes are associated with hyperuricemia, most individuals with hyperuricemia may never develop a clinical event from urate crystal deposition. 

A condition known as Lesch-Nyhan syndrome is one of the primary causes of gout. An X-linked recessive trait occurring in males, this condition involves a tremendous overproduction of uric acid due to a deficiency of one of the enzymes involved in purine metabolism, hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Other abnormalites lead to mental retardation and aggressive behavior. An obvious symptom of the condition is self-mutilation. 

Forsyth KM, Bjur RA, Westfall DP (1991) Nucleotide modulation of norepinephrine release from sympathetic nerves in the rat vas deferens. J Pharmacol Exp Ther 1256 821-6 Franco R, Canela El, Bozal J (1986) Enzymes of the purine metabolism in rat brain microsomes. NeurochemRes 11 407-22... 

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