Guanase from Human Liver — Purification and Characterisation

Kuzmits, R.; Stemberger, H; Müller, Mathias M.

doi:10.1007/978-1-4684-8559-2_31

Cited by 9 publications

(4 citation statements)

References 3 publications

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“…Guanine is not detectable in cells and extracellular fluids because it is metabolised to xanthine by guanine aminohydrolase, guanase (EC 3.5.4.3). This enzyme is widely distributed in human tissues Kuzmits et al, 1980) and has an apparent Km of <l~motL -1 for its substrate. In contrast xanthine oxidase has a limited tissue distribution (Watts et al, 1965;Bruder et al, 1983;Parks and Granger, 1986) and a higher apparent Km of 9#mol L -1 (Krenitsky et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

“…Two factors seem to have limited progress, one is the widespread therapeutic use of the xanthine oxidase (EC 1.2.3.2) inhibitor, allopurinol, which distorts purine metabolism and the other is the limited sensitivity and specificity of earlier analytical methods for the main substrates of the missing enzyme, hypoxanthine and guanine. The latter is not detectable in tissues and body fluids due to its rapid conversion to x:anthine (Van Waeg et al, 1986;Kuzmits et al, 1980) which is measurable.…”

Section: Introductionmentioning

confidence: 99%

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Lesch‐Nyhan syndrome and its pathogenesis: Purine concentrations in plasma and urine with metabolite profiles in CSF

Harkness

McCreanor

Watts

1987

J of Inher Metab Disea

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Purine metabolism in the Lesch-Nyhan syndrome has been re-examined in 10 patients. Hypoxanthine and xanthine concentrations in plasma and CSF and urinary excretion have been studied, on and off allopurinol treatment, using high performance liquid chromatographic methods. Accumulation of the substrate, hypoxanthine, of the missing hypoxanthine guanine phosphoribosyltransferase (HPRT) enzyme, is more marked in urine and in CSF than in plasma. The greater increase in CSF is consistent with the most metabolically active tissue, brain, showing the most marked functional changes. The function of HPRT seems to be the recycling of hypoxanthine which is released from tissues in increasing quantities as energy use, ATP 'turnover', in the tissue increases. The existing screening method for HPRT deficiency, the ratio of the urinary concentration of urate to that of creatinine, shows overlap between the values in severe HPRT deficiency and in controls; this overlap is not found with a urinary hypoxanthine/creatinine molar concentration ratio.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lesch‐Nyhan syndrome and its pathogenesis: Purine concentrations in plasma and urine with metabolite profiles in CSF

Harkness

McCreanor

Watts

1987

J of Inher Metab Disea

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“…In normal people the origin of a small proportion of the urinary xanthine can be from hypoxanthine; after exercise hypoxanthine excretion rose 20-fold, xanthine excretion only twofold (Table 4). However, the high excretion of xanthine in xanthine oxidase deficiency probably arises from the turnover of guanine nucleotides (Bradford et al, 1968) through guanine deaminated by the widely distributed enzyme (Kuzmits et at., 1980) guanase (EC 3.5.4.3) to xanthine. Since xanthine is a poor substrate for the salvage enzyme hypoxanthine guanine phosphoribosyltransferase, (EC 2.4.2.8) showing only about 0.3 % of the activity with hypoxanthine and guanine (Kelley et al, 1967) the quantitative excretion of xanthine in Table 4 may be a large proportion of the turnover of guanine nucleotides.…”

Section: Renal Handling and Origins Of Oxypurinesmentioning

confidence: 99%

Xanthine oxidase deficiency and ‘Dalmatian’ hypouricaemia: Incidence and effect of exercise

Harkness

Coade

Walton

et al. 1983

J of Inher Metab Disea

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In order to study the effects of raising the hypoxanthine concentration in plasma on its metabolism and renal handling, the effects of intense exercise have been investigated in a patient with xanthine oxidase deficiency. Despite the 90-fold increased concentration of hypoxanthine in plasma above resting levels in normal individuals, the intracellular concentration of the initial product of hypoxanthine in cells, IMP, was unaffected. Evolution may have stabilized intracellular nucleotide concentrations against the large fluctuations in plasma hypoxanthine which occur during exercise. The renal handling of hypoxanthine is consistent with 'filtration'. In contrast, xanthine clearances may exceed those for creatinine and urinary concentrations do not correlate with those for creatinine; 'secretion' may be involved. Xanthine excretion may reflect guanine breakdown. A retrospective survey of urate concentrations in blood from 47 420 patients followed by further selected investigations detected 2 women with persistent marked hypouricaemia and high urinary urate clearances, 'Dalmatian' hypouricaemia. High pressure liquid chromatographic analysis of plasma extracts can distinguish xanthine oxidase deficiency from other causes of hypouricaemia.

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“…Guanase is thought to be contained mostly in liver, brain and kidneys, but little in other tissues, and thus there are few reports in which guanase has been examined in other tissues. Levine et al (18) and Kuzumits et al (16) identified guanase activity in large and small intestines other than liver, brain and kidneys, though to a small extent, but little activity in other tissues. The authors' histochemical results revealed guanase activity in liver cytoplasm to a great extent, and also in kidneys' proximal tubuli and mucosal epithelium of small intestine to the same extent as in liver.…”

Section: Discussionmentioning

confidence: 98%

Histochemical distribution of guanase in human tissues with guanine in bicine buffer as substrate.

Ito

Hayashi

Iwasaki

et al. 1986

Acta Histochem. Cytochem

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Guanase from Human Liver — Purification and Characterisation

Cited by 9 publications

References 3 publications

Lesch‐Nyhan syndrome and its pathogenesis: Purine concentrations in plasma and urine with metabolite profiles in CSF

Lesch‐Nyhan syndrome and its pathogenesis: Purine concentrations in plasma and urine with metabolite profiles in CSF

Xanthine oxidase deficiency and ‘Dalmatian’ hypouricaemia: Incidence and effect of exercise

Histochemical distribution of guanase in human tissues with guanine in bicine buffer as substrate.

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