9- guanine variants

FIGURE 9.14 Variant forms of DNA. (a) A cruciform, a triplex, and Z-DNA (top to bottom), (b) A quadruplex formed when repeated guanine bases align two DNA strands. Images courtesy of KM. Vasquez. From G. Wang and K.M. Vasquez, Mutation Research >2006 Elsevier. 

T. Page, B. Bakay, E. Nissinen and W.I. Nyhan. Hjrpoxanthine-guanine Phosphoribosyltransferase Variants Correlation of Clinical Phenotype With Enzyme Activity. J. Inherited Metab. Pis. 4 ... 

J. Dancis, L. C. Yip, R. P. Cox, S, Piomelli, M. E. Balls. Disparate enzyme activity in erythrocytes and leucocytes a variant of hypoxanthine-guanine phosphoribosyl transferase deficiency with an unstable enzyme. J.Clin.Invest., 52 206 (1973). 

T. Page, B. Bakey, E. Nissinen, W. L. Nyhan. Hypoxanthine-guanine phosphoribosyl transferase variants correlation of clinical phenotype with enzyme activity. J.Inher.Metab.Pis.,... 

Bakay, B. and Nyhan, W.L. 1972. Activation of variants of hypoxanthine-guanine phosphoribosyltransferase by normal enzyme. Proc. Nat. Acad. Sci. (U.S.A.). 2523-2527. 

In the Lesch-Nyhan syndrome, hypoxanthine-guanine phosphoribosyltransferase is virtually absent [125], an unstable variant enzyme being present, and, in consequence, guanylic and inosinic acids are not formed from guanine and hypoxanthine. The feed-back inhibition is therefore deficient and the rate of purine biosynthesis is elevated [126]. Uric acid is produced at five to six times the normal rate and at three times the rate, corrected for body weight, found in adults vyith gout. The concentration of uric acid in the blood lies between 8 and 15 mg per 100 ml (normal 5.6 1.1 gouty subjects 9.2 1.1). 

In > 95% of the sufferers from gout, the activity of hypoxanthine-guanine phosphoribosyltransferase is normal, but in a minority (< 5%) this activity is low [133]. These patients have a tendency to early development of arthritis and nephropathy. About one-third of them, those in whom the activity of the enzyme is lowest, show some neurological abnormalities, particularly mental retardation. This type of gout is related to variant forms of hypoxanthine-guanine phosphoribosyltransferase, a different variant in each family, the activity being up to 1% of normal [127]. In some families, the variant enzyme shows different activities towards hypoxanthine and guanine. 

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