Hypoxanthine uptake by human erythrocytes

Giacomello, Alessandro; Salerno, C

doi:10.1016/0014-5793(79)80495-0

Cited by 23 publications

(10 citation statements)

References 5 publications

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“…It is well known that PRPP synthetase is markedly stimulated by Pi [1][2][3], and that the reaction is inhibited by physiological concentrations of 2,3-BPG and nucleoside diphosphates, i.e. ADP in human erythrocytes [3,7,12]. Here we show by 31P-n.m.r.…”

Section: Identification Of Prppsupporting

confidence: 55%

“…3b). A decrease in the inhibitory action of 2,3-BPG could also be involved [12], although this possibility seems more unlikely, as discussed below.…”

Section: Effect Of Incubation Conditions On Prpp Accumulationmentioning

confidence: 99%

“…In the human erythrocyte the concentration of PRPP is normally about 1-6 #aM [4][5][6], and the rate of synthesis is reported to be regulated in a complex manner by the concentration of Pi and the inhibitory actions of 2,3-bisphosphoglycerate (2, and nucleoside diphosphates and product inhibition by PRPP [1][2][3]7,8]. It had earlier been shown that incubation of human erythrocytes in media containing different concentrations ofvarious purines, purine nucleosides and Pi yields variable stimulation of PRPP synthesis [3,[9][10][11][12][13]. Recently it was shown that adenine uptake in human erythrocytes, in contrast with hypoxanthine uptake [12], is independent of conditions known to stimulate PRPP synthesis such as low pH and high Pi concentrations [14].…”

mentioning

confidence: 99%

“…It had earlier been shown that incubation of human erythrocytes in media containing different concentrations ofvarious purines, purine nucleosides and Pi yields variable stimulation of PRPP synthesis [3,[9][10][11][12][13]. Recently it was shown that adenine uptake in human erythrocytes, in contrast with hypoxanthine uptake [12], is independent of conditions known to stimulate PRPP synthesis such as low pH and high Pi concentrations [14].…”

mentioning

confidence: 99%

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Inosine/pyruvate/phosphate medium but not adenosine/pyruvate/phosphate medium introduces millimolar amounts of 5-phosphoribosyl 1-pyrophosphate in human erythrocytes. A 31P-n.m.r. study

Petersen

Quistorff

1990

Biochemical Journal

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Incubation of human erythrocytes in medium containing inosine (10 mM), pyruvate (10 mM), phosphate (50 mM) and NaCl (75 mM) at pH 6.6 leads to a more than 1000-fold increase in the concentration of 5-phosphoribosyl 1-pyrophosphate (PRPP), as identified and quantified by 31P-n.m.r. spectroscopy. The accumulation is highly pH-dependent, with a maximum at extracellular pH 6.60, and the maximum value of 1.3-1.6 mmol/l of erythrocytes is attained within 1 h at 37 degrees C. PRPP was accumulated despite high concentrations of 2,3-bisphosphoglycerate (2,3-BPG), an inhibitor of PRPP synthetase. The concentration of PRPP correlated with the intracellular concentration of inorganic phosphate (Pi). Substitution of either adenosine or adenosine plus inosine for inosine in the medium did not lead to 31P-n.m.r.-detectable accumulation of PRPP. These results show that neither 2,3-BPG nor PRPP itself inhibits the synthesis of PRPP in the human erythrocyte. Adenosine, however, prevents the inosine-stimulated accumulation of PRPP.

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Section: Identification Of Prppsupporting

confidence: 55%

“…3b). A decrease in the inhibitory action of 2,3-BPG could also be involved [12], although this possibility seems more unlikely, as discussed below.…”

Section: Effect Of Incubation Conditions On Prpp Accumulationmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Inosine/pyruvate/phosphate medium but not adenosine/pyruvate/phosphate medium introduces millimolar amounts of 5-phosphoribosyl 1-pyrophosphate in human erythrocytes. A 31P-n.m.r. study

Petersen

Quistorff

1990

Biochemical Journal

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“…The salvage of hypoxanthine to inosine 5'-monophosphate (IMP)' depends on the concentration ofinorganic phosphate (Pi) in the medium (2-4, 6, 7). This is ascribed to stimulation by Pi of the synthesis of 5-phosphoribosyl-l-pyrophosphate (PRPP), a cosubstrate and rate limiting factor in the phosphoribosylation of hypoxanthine to IMP (4,7). Whereas PRPP synthetase is activated by Pi, it is inhibited by ADP, GDP, and 2,3-bisphosphoglycerate (2, (8,9).…”

Section: Introductionmentioning

confidence: 99%

Oxypurine cycle in human erythrocytes regulated by pH, inorganic phosphate, and oxygen.

Berman¹,

Black²,

Human³

et al. 1988

J. Clin. Invest.

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The effect of pH, P02, and inorganic phosphate on the uptake and metabolism of hypoxanthine by erythrocytes has been studied. Uptake of hypoxanthine and accumulation of inosine 5'-monophosphate (IMP) were markedly increased at acid pH, high external phosphate concentrations, and low Po2. Release of accumulated IMP as hypoxanthine occurred at alkaline pH values and low external phosphate concentrations. Conditions favoring IMP accumulation gave rise, in the absence of hypoxanthine, to a corresponding increase in 5'-phosphoribosyl-1-pyrophosphate. Intracellular phosphate concentrations were markedly pH dependent and a model is presented whereby hypoxanthine uptake and release are controlled by intracellular concentrations of inorganic phosphate and 2,3-bisphosphoglycerate. These allosteric effectors influence, in opposing ways, two enzymes governing IMP accumulation, namely 5'-phosphoribosyl-l-pyrophosphate synthetase and 5'-nucleotidase. These metabolic properties suggest that the erythrocyte could play a role in the removal of hypoxanthine from anoxic tissue.

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