Developmental changes in purine phosphoribosyltransferases in human and rat tissues

Adams, Alexander T.; Harkness, R. A.

doi:10.1042/bj1600565

Cited by 55 publications

(27 citation statements)

References 53 publications

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“…The activity in the fetal tis sues studied was of the same magnitude as that reported by Boyle et al [1970], and Adams and Harkness [1976] but in the liver somewhat lower than in the trophoblast [Vettenranta and Raivio, 1988a], The Km for hypoxanthine in our material (ca. 60 pM) was an order of magnitude higher than that estimated by Adams and Harkness (5-9 pM) [ 1976], but close to that reported by Ikeda et al [1986] for adult brain (50 pM).…”

Section: Discussionsupporting

confidence: 63%

“…Adams and Harkness [1976] also found a substantial increase in the postnatal HGPRT activity of brain and liver, and suggested this to be a developmental phenomenon. Yet, they were unable to demonstrate the same in their fetal material, probably due to the small number of samples.…”

Section: Discussionmentioning

confidence: 96%

“…The activity of HGPRT has been evalu ated in a variety of human fetoplacental tis sues, including cultured amniotic fluid cells [Fujimotoet al, 1968], chorionic villi [Stout et al, 1985], some fetal tissues [Adams and Harkness, 1976;Boyle et al, 1970], and the trophoblast [Vettenranta and Raivio, 1988a], Of the fetal tissues analyzed in these studies, the highest activity was recorded in the brain, and the trophoblastic acivity ap peared to be of the same magnitude. Adams and Harkness [1976] also found a substantial increase in the postnatal HGPRT activity of brain and liver, and suggested this to be a developmental phenomenon.…”

Section: Discussionmentioning

confidence: 99%

“…For the reutilization of catabolized pu rines, hypoxanthine/guanine phosphoribo syltransferase (HGPRT) is in a key position, since it is rate limiting for the uptake of the main physiological purine base, hypoxanthine. Each of these enzymes has been stud ied in human fetal tissues [Adams and Harkness, 1976;Amano et al, 1985;Boyle et al, 1970;Fujimoto et al, 1968;Kaletha et al, 1987;Kaletha and Nowak, 1988;Stout et al, 1985], Our aim was to follow the developmental changes in the activities and kinetic charac teristics of these three enzymes in the same tissue samples from human fetuses, to gain insight into the predominant metabolic pathways and their regulation. Additionally, we wanted to compare these enzyme activi ties to those present in the metabolically most active part of the placenta, the trophoblast [Vettenranta, 1988;Vcttenranta andRaivio, 1984, 1988a, b].…”

Section: Introductionmentioning

confidence: 99%

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Key Enzymes of Purine Degradation and Reutilization in Human Fetal Liver and Brain

Vettenranta

Raivio²

1990

Neonatology

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The activities and kinetic parameters of 5′-nucleotidase, adenosine monophosphate (AMP) deaminase, and hypoxanthine/guanine phosphoribosyltransferase (HGPRT) were assayed in human fetal brain and liver. The apparent activity of 5′-nucleotidase decreases in the liver and increases in the brain with gestation. Its apparent K_m is about 27 μM for AMP in the brain at term and liver throughout gestation but about 60 μM in the premature brain. The activity of (AMP) deaminase in the liver increases, while that in the brain does not significantly change with gestation. Its apparent Km for AMP is about 5 mM in the tissues studied. The activity of HGPRT increases with gestation in both the fetal brain and liver, and is altogether high in the fetal brain. Its apparent K_m for hypoxanthine appears to be high, about 59 μM, in the tissues studied. The activities measured reflect the maximal capacities of the enzymes. Conclusions concerning their in vivo activities cannot, however, be based on studies employing disrupted cells.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Key Enzymes of Purine Degradation and Reutilization in Human Fetal Liver and Brain

Vettenranta

Raivio²

1990

Neonatology

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“…In the rat testis, the specific activity of purine phosphoribosyl transferase is markedly higher than that of amidophosphoribosyltransferase. 7,8) Rat testis also has a high activity of uridine kinase, a rate-limiting enzyme of the pyrimidine salvage pathway. 9) Accordingly, the salvage pathway is likely to play a prominent role in nucleotide biosynthesis in testis.…”

mentioning

confidence: 99%

Characterization of Nucleobase Transport by Mouse Sertoli Cell Line TM4

Kato

Maeda

Akaike

et al. 2009

Biological & Pharmaceutical Bulletin

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In the spermatogenesis, many nucleosides and nucleobases are needed for the salvage nucleotide biosynthesis. One of the roles of Sertoli cells is to provide such nutrients to spermatogenic cells located within the bloodtestis barrier (BTB). We have already shown that nucleoside transporters are expressed and are functional in primary-cultured rat Sertoli cells and TM4 cells derived from mouse testis. Here, we examined the uptakes of purine ([ 3 H]guanine) and pyrimidine ([ 3 H]uracil) nucleobases using TM4 cells. Uptakes of both nucleobases were time-and concentration-dependent, and kinetic analysis indicated the involvement of high-affinity transport systems. Uptake of uracil was significantly reduced in the absence of Na ؉ , although guanine uptake was mainly mediated by a sodium-independent transport system in TM4 cells. Guanine uptake was inhibited by other purine nucleobases, but not by pyrimidine nucleobases. Only pyrimidine nucleobases reduced uracil uptake. In addition, mycophenolic acid, an inosine monophosphate dehydrogenase inhibitor, up-regulated guanine uptake. These results suggested that there are distinct transport systems for purine and pyrimidine nucleobases in cells of mouse Sertoli cell line TM4.

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Impaired differentiation of HPRT-deficient dopaminergic neurons: A possible mechanism underlying neuronal dysfunction in Lesch-Nyhan syndrome

1998

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Lesch-Nyhan syndrome is a hereditary disorder of purine metabolism causing overproduction of uric acid and neurological problems including spasticity, choreoathetosis, mental retardation, and compulsive self-mutilation. The syndrome is caused by a defect in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT), which converts guanine and hypoxanthine to the nucleotides GMP and IMP. There is evidence that the neurological problems are due to an adverse effect of the HPRT deficiency on the survival and/or development of dopaminergic neurons, specifically. Here we report that HPRT-deficient PC12 mutants that have a normal or near normal dopamine content (55-97% of that of wild-type cells) fail to undergo neuronal differentiation induced by nerve growth factor (NGF) when the de novo pathway of purine synthesis is partially inhibited. However, nerve growth factor-induced differentiation is near normal under these conditions in PC12 HPRT-deficient mutants containing much lower dopamine levels (<8% of that of wild type cells), indicating a neurotoxic effect of the endogenous dopamine in the mutants. The degree of inhibition of the de novo pathway of purine synthesis was the same in both classes of HPRT-deficient mutants. Expression of BCl-2 in a PC12 mutant that has a normal dopamine content allowed partial NGF-induced differentiation suggesting that the apoptotic pathway might be involved in the failure of differentiation when the de novo pathway of purine synthesis is partially inhibited.

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Developmental changes in purine phosphoribosyltransferases in human and rat tissues

Cited by 55 publications

References 53 publications

Key Enzymes of Purine Degradation and Reutilization in Human Fetal Liver and Brain

Key Enzymes of Purine Degradation and Reutilization in Human Fetal Liver and Brain

Characterization of Nucleobase Transport by Mouse Sertoli Cell Line TM4

Impaired differentiation of HPRT-deficient dopaminergic neurons: A possible mechanism underlying neuronal dysfunction in Lesch-Nyhan syndrome

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