Inosinic Acid Dehydrogenase Activity in the Lesch-Nyhan Syndrome

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1972 Jun 1

PMID 5024037

Citations 6

Authors

D M Pehlke

J A McDonald

E W Holmes

W N Kelley

Affiliations

Soon will be listed here.

Abstract

Inosinic acid dehydrogenase was evaluated in normal subjects and in patients with the Lesch-Nyhan syndrome. A significant difference in activity was found between erythrocytes derived from normal controls (1.21+/-0.47 pmoles/hr per mg protein) and from 15 patients with the Lesch-Nyhan syndrome (6.72+/-6.23 pmoles/hr per mg protein). However, no difference in activity was demonstrable in muscle or leukocytes derived from normal and Lesch-Nyhan patients. The increased activity of inosinic acid dehydrogenase in erythrocytes from patients with the Lesch-Nyhan syndrome is due to stabilization of the enzyme in vivo as well as the absence of an inhibitor which is present in erythrocytes from normal subjects.

Citing Articles

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Protein variations associated with Lesch-Nyhan syndrome.

Merril C, Goldman D, Ebert M Proc Natl Acad Sci U S A. 1981; 78(10):6471-5.

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Human phosphoribosylpyrophosphate synthetase: increased enzyme specific activity in a family with gout and excessive purine synthesis.

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Inosine 5'-phosphate dehydrogenase activity in normal and leukemic blood cells.

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References

Seegmiller J, Rosenbloom F, Kelley W . Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science. 1967; 155(3770):1682-4. DOI: 10.1126/science.155.3770.1682. View

Chodirker W, Bock G, Vaughan J . Isolation of human PMN leukocytes and granules: observations on early blood diluion and on heparin. J Lab Clin Med. 1968; 71(1):9-19. View

Rosenbloom F, HENDERSON J, CALDWELL I, Kelley W, Seegmiller J . Biochemical bases of accelerated purine biosynthesis de novo in human fibroblasts lacking hypoxanthine-guanine phosphoribosyltransferase. J Biol Chem. 1968; 243(6):1166-73. View

Anderson J, Sartorelli A . Inosinic acid dehydrogenase of sarcoma 180 cells. J Biol Chem. 1968; 243(18):4762-8. View

Rubin C, BALIS M, Piomelli S, BERMAN P, DANCIS J . Elevated AMP pyrophosphorylase activity in congenital IMP pyrophosphorylase deficiencey (Lesch-Nyhan disease). J Lab Clin Med. 1969; 74(5):732-41. View

Greene M, Boyle J, Seegmiller J . Substrate stabilization: genetically controlled reciprocal relationship of two human enzymes. Science. 1970; 167(3919):887-9. DOI: 10.1126/science.167.3919.887. View

Saccoccia Jr P, MIECH R . Inosinic acid dehydrogenase in mammalian tissues. Mol Pharmacol. 1969; 5(1):26-9. View

Ghadimi H, Bhalla C, Kirchenbaum D . The significance of the deficiency state in Lesch-Nyhan disease. Acta Paediatr Scand. 1970; 59(3):233-40. DOI: 10.1111/j.1651-2227.1970.tb08998.x. View

STRAND L, Felsher B, Redeker A, MARVER H . Heme biosynthesis in intermittent acute prophyria: decreased hepatic conversion of porphobilinogen to porphyrins and increased delta aminolevulinic acid synthetase activity. Proc Natl Acad Sci U S A. 1970; 67(3):1315-20. PMC: 283354. DOI: 10.1073/pnas.67.3.1315. View

10.

Fox I, Kelley W . Phosphoribosylpyrophosphate in man: biochemical and clinical significance. Ann Intern Med. 1971; 74(3):424-33. DOI: 10.7326/0003-4819-74-3-424. View

11.

LOWRY O, ROSEBROUGH N, FARR A, RANDALL R . Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265-75. View

12.

MAGASANIK B, Moyed H, GEHRING L . Enzymes essential for the biosynthesis of nucleic acid guanine; inosine 5'-phosphate dehydrogenase of Aerobacter aerogenes. J Biol Chem. 1957; 226(1):339-50. View

13.

HENNESSEY M, WALTERSDORPH A, Huennekens F, GABRIO B . Erythrocyte metabolism. VI. Separation of erythrocyte enzymes from hemoglobin. J Clin Invest. 1962; 41:1257-62. PMC: 291040. DOI: 10.1172/JCI104588. View

14.

Lesch M, Nyhan W . A FAMILIAL DISORDER OF URIC ACID METABOLISM AND CENTRAL NERVOUS SYSTEM FUNCTION. Am J Med. 1964; 36:561-70. DOI: 10.1016/0002-9343(64)90104-4. View

15.

Danon D, MARIKOVSKY V . DETERMINATION OF DENSITY DISTRIBUTION OF RED CELL POPULATION. J Lab Clin Med. 1964; 64:668-74. View

16.

Moyed H . Interference with feedback control of enzyme activity. Cold Spring Harb Symp Quant Biol. 1961; 26:323-9. DOI: 10.1101/sqb.1961.026.01.039. View

17.

SALSER J, BALIS M . THE MECHANISM OF ACTION OF 6-MERCAPTOPURINE. II. BASIS FOR SPECIFICITY. Cancer Res. 1965; 25:544-51. View

18.

TSCHUDY D, Perlroth M, MARVER H, Collins A, HUNTER Jr G, RECHCIGL Jr M . ACUTE INTERMITTENT PORPHYRIA: THE FIRST "OVERPRODUCTION DISEASE" LOCALIZED TO A SPECIFIC ENZYME. Proc Natl Acad Sci U S A. 1965; 53:841-7. PMC: 221077. DOI: 10.1073/pnas.53.4.841. View