The development of hypoxanthine-guanine phosphoribosyltransferase activity in man

Adams, Alexander T.; Anderson, James M.; Nicol, A D; Harkness, R. A.

doi:10.1042/bj1250036pa

Cited by 10 publications

(4 citation statements)

References 2 publications

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“…guanosine phosphorylase (EC 2.4.2.15), inosine phosphorylase (EC 2.4.2.1) and adenosine deaminase (EC 3.5.4.4), although such methods have yielded useful results. The present method (Adams et al, 1971) and several subsequent methods have avoided these difficulties by inhibiting 5'-nucleotidase almost completely with 1.5mM-dTTP (Murray & Friedrichs, 1969;Fujimoto & Seegmiller, 1970).…”

Section: Discussionmentioning

confidence: 95%

“…Radioautographic studies on the location of hypoxanthine/guanine phosphoribosyltransferase in the testes ofchildren showed that there was much activity throughout the sections, with the highest concentrations in the basal cells of the seminiferous tubules in the spermatogonia. Thyroid used as a control tissue showed virtually no activity (Adams, 1973). .-One foetal testis and a foetal ovary both showed .considerable activity, 203 and 130nmol/h per mg of protein rbspectively; but no activitywas,dettable in the ovary of a child aged 7, years.…”

Section: Erythrocyte Purine Phosphoribosyltransferase Activities In Manmentioning

confidence: 90%

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Developmental changes in purine phosphoribosyltransferases in human and rat tissues

Adams

Harkness

1976

Biochemical Journal

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1. The hypoxanthine/guanine and adenine phosphoribosyltransferase activities in a wide variety of human tissues were studied during their growth and development from foetal life onward. A wide range of activities develop after birth, with especially high values in the central nervous system and testes. 2. Postnatal development of hypoxanthine/guanine phosphoribosyltransferase was also defined in the rat. Although there were increases in the central nervous system and testes, there was also a rise in activity in the liver, which was less marked in man. 3. A sensitive radiochemical assay method, using dTTP to inhibit 5'-nucleotidase activity, suitable for tissue extracts, was developed. 4. No definite evidence of the existence of tissue-specific isoenzymes of hypoxanthine/guanine or adenine phosphoribosyltransferase was found. Hypoxanthine/guanine phosphoribosyltransferase in testes, however, had a significantly different thermal-denaturation rate constant. 5. The findings are discussed in an attempt to relate activity of hypoxanthine/guanine phosphoribosyltransferase to biological function. Growth as well as some developmental changes appear to be related to increase in the activity of this enzyme.

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Section: Discussionmentioning

confidence: 95%

Section: Erythrocyte Purine Phosphoribosyltransferase Activities In Manmentioning

confidence: 90%

Developmental changes in purine phosphoribosyltransferases in human and rat tissues

Adams

Harkness

1976

Biochemical Journal

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“…The largest difference, which is that seen between basal ganglia and the cerebral cortex is only twofold (Kelley et al, 1969). This apparent difference may be further diminished when account is taken of the 5' nucleotidase (5' ribonucleotide phosphohydrolase EC 3.1.3.5) activity in different parts of the brain (Adams et al, 1971;Adams, 1973). Factors other than the absolute levels of HGPRT may be important in determining the evolution of brain damage in the Lesch-Nyhan syndrome.…”

Section: Discussionmentioning

confidence: 99%

Clinical and biochemical studies on treatment of Lesch-Nyhan syndrome

Watts¹,

McKeran²,

Brown³

et al. 1974

Archives of Disease in Childhood

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“…Hypotheses to explain hyperuricemia and the development of neurologic dysfunction have been examined in detail [10,37,44]. H-G PRT has high activity in fetal brain [1,39], and values rise to the higher values of adult brain shortly after birth [1]. Although enzyme activity is particularly high in basal ganglia [39], pathologic study of the central nervous system in autopsied cases does not reveal specific anatomic lesions [42,51].…”

Section: Discussionmentioning

confidence: 99%

Adenine and Folic Acid in the Lesch-Nyhan Syndrome

Benke¹,

Herrick²,

Smitten³

et al. 1973

Pediatr Res

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Therapy of identical twin males with the enzyme defect of the Lesch-Nyhan (L-N) syndrome was instituted at 12 hr of age with adenine, 10 mg/kg/24 hr, administered to one twin and folic acid, 15 mg/24 hr, to both. At 4 years of age both twins demonstrate delayed neurologic development and spasticity but are less severely affected than most other patients with this disorder. Administered in subsequent studies to two maternal cousins of the twins who had clinical features of the L-N syndrome and absence of erythrocyte hypoxanthine-guanine phosphoribosyltransferase activity were adenine, 10 mg/kg/24 hr, adenine, 40 mg/kg/24 hr, folic acid, and monosodium glutamate. Low dose adenine had a slight suppressive effect on glycine-1-14 C incorporation into uric acid; high dose adenine had a strong suppressive effect in the second patient. We conclude that the adenine dose chosen for therapy was too low. 2,8-Dihydroxyadenine, a toxic breakdown product of adenine, was detected in the urine at both adenine dose levels. Folic acid and monosodium glutamate in these patients further stimulate accelerated glycine-ll4 C incorporation into uric acid. In vitro transport studies, performed with inverted hamster jejunal preparations, suggest that adenine is largely converted to adenine monophosphate when exposed to the mucosal surface. This may limit the passage of orally administered adenine to the central nervous system in patients. Adenine and purine precursors affect the biochemical pathology of the L-N syndrome, in vivo and in vitro, but therapeutic use of adenine, 10 mg/kg/24 hr, and folic acid started on the 1st day of life did not prevent central nervous system dysfunction. Speculation

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The development of hypoxanthine-guanine phosphoribosyltransferase activity in man

Cited by 10 publications

References 2 publications

Developmental changes in purine phosphoribosyltransferases in human and rat tissues

Developmental changes in purine phosphoribosyltransferases in human and rat tissues

Clinical and biochemical studies on treatment of Lesch-Nyhan syndrome

Adenine and Folic Acid in the Lesch-Nyhan Syndrome

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