Metabolism and salvage of adenine and hypoxanthine by myocytes isolated from mature rat heart

Brown, Anne K.; Raeside, D.; Bowditch, Julia; Dow, Jocelyn W.

doi:10.1016/0167-4889(85)90213-7

Cited by 31 publications

(10 citation statements)

References 21 publications

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“…Hence, we tested the ability of ribose to overcome the glucose deficiency in FSH-treated, hypoxanthine-arrested oocytes. Consistent with other studies in which exogenous ribose augmented levels of PRPP and purine nucleotide production [46][47][48], this pentose stimulated meiotic maturation, though it was effective at lower concentrations in the presence of FSH. These findings bolster the idea that end products of the oxidative arm of the PPP participate in meiotic induction.…”

Section: Discussionsupporting

confidence: 91%

“…Some cells can utilize exogenous ribose, converting it to ribose-5-phosphate and thereafter to PRPP and purine nucleotides, thus obviating a requirement for the oxidative arm of the PPP for purine synthesis [46][47][48][49]. To determine whether ribose could serve a similar function in the present system, cumulus cell-enclosed oocytes were cultured for 17-18 h in hypoxanthine-supplemented medium lacking glucose and containing 0.1 mM pyruvate, in the presence or absence of FSH.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Meiotic Induction in Cumulus Cell-Enclosed Mouse Oocytes: Involvement of the Pentose Phosphate Pathway1

Downs¹,

Humpherson²,

Leese³

1998

Biology of Reproduction

127

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In this study we tested the hypothesis that the pentose phosphate pathway (PPP) participates in the meiotic induction of mouse oocytes. The electron acceptors methylene blue, phenazine ethosulfate (PES), and pyrroline-5-carboxylate (P5C) oxidize NADPH to NADP and activate the NADP-dependent enzymes of the PPP. Each of these compounds triggered a dose-dependent increase in meiotic maturation in hypoxanthine-arrested cumulus cell-enclosed oocytes during 17- to 18-h cultures. More than 96% of the oocytes underwent germinal vesicle breakdown (GVB) at the highest concentrations of P5C and PES tested (250 and 1 microM, respectively) as compared to only 45-52% of control oocytes. P5C was also stimulatory to denuded oocytes. Analysis of energy substrates in microdrop cultures revealed a 3.6-fold increase in glucose consumption by PES-treated oocyte-cumulus cell complexes that was associated with stimulation of GVB. On the other hand, 2-deoxyglucose, which interferes with glucose utilization, prevented the induction of maturation brought about by P5C. Apocynin and diphenyleneiodonium, inhibitors of NADPH oxidase, prevented meiotic maturation in the presence or absence of FSH. Gonadotropin-induced maturation was also prevented by 6-aminonicotinamide (6-AN) and dehydroepiandrosterone (DHEA), inhibitors of the two NADP-dependent enzymes of the PPP, and this was accompanied by suppression of glucose consumption. Phosphoribosyl-pyrophosphate (PRPP) is an important compound required in purine metabolism and can be formed from the end product of the oxidative arm of the PPP, ribose-5-phosphate. Ribose, which can be metabolized to PRPP, increased PRPP synthesis in complexes and induced meiotic maturation when added to hypoxanthine-arrested cumulus cell-enclosed oocytes in glucose-free medium in both the presence and absence of FSH. PRPP levels within complexes were also increased by glucose and FSH, but were reduced by hypoxanthine, 6-AN, and DHEA. In addition, exogenous PRPP stimulated maturation in hypoxanthine-arrested oocytes. These results support the proposition that glucose metabolism through the PPP is important in the meiotic induction mechanism and may involve the generation of PRPP that acts, at least in part, through the purine metabolizing pathways.

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Section: Discussionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Meiotic Induction in Cumulus Cell-Enclosed Mouse Oocytes: Involvement of the Pentose Phosphate Pathway1

Downs¹,

Humpherson²,

Leese³

1998

Biology of Reproduction

127

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“…We thus investigated the effect of phosphate-free perfusion on the distribution of radioactivity between soluble and sequestered nucleotide. In an effort to avoid the possible compartmentation of precursor in the tissue (see above), the nucleotides were labelled using [8-I4C]adenine in the presence of D(-)ribose which Dow and her co-workers [22] have shown is readily incorporated into the nucleotide pool in isolated myocytes from mature rats. Uptake of adenine into nucleotide in perfused heart was much slower than with adenosine even at a 40 times higher precursor concentration and improved by recirculating the perfusate.…”

Section: The Estimation Of (Pg-atp)n In Heartsmentioning

confidence: 99%

Evidence that the recently discovered high‐energy nucleotide derivative, oligo(phosphoglyceroyl‐ATP) forms the end chains of purinogen, a complex polymeric major stroage form of adenine nucleotide and phosphate in heart

Patel

Sarcina

Mowbray

1994

European Journal of Biochemistry

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Previous work in our laboratory has shown that free adenine nucleotides in heart, liver and kidney exchange rapidly with a major acid-insoluble species which we have characterised as oligo[3-phospho-glyceroyl-y-triphospho(5')adenosine(3')], abbreviated to (PG-ATP),. This has been found in liver and in heart to be complexed to a specific 3'-phosphodiesterase which releases PG-ATP monomers and is located in mitochondrial inter-membrane space. In ['4C]adenosine-perfused hearts, (PG-ATP), has been shown to reach specific radioactivity equilibrium with free ATP within 30 min. Attempts to estimate the quantities of nucleotide in (PG-ATP), and free nucleotides in response to a variety of stimuli using previously labelled hearts showed by contrast that the free and sequestered nucleotide pools were not at equilibrium. Re-examination of the rapidly labelled acid-insoluble species led to the recognition of radioactive inhomogeneity and of three additional nucleotide components. Perfusion of hearts with phosphate-free medium increased the proportion of 14C incorporated into the sequestered form by 70% and caused the net transfer of 0.9 pmol . g-' of purine from free adenine nucleotides to the sequestered form. The findings point to the existence of a more complex polymer whose rapidly exchanging end chains we had previously isolated and characterised as (PG-ATP),; we suggest the name purinogen for this polymer and show that it can contain between 25 % and 55 % of the tissue nucleotide pool in rat heart. Large changes in the amounts of adenine nucleotides extracted at different times from steady-state perfused rat hearts could not be explained by interconversion with known derivatives or polymers and led us to propose that some unknown major source of nucleotides capable of rapid exchange with the known nucleotides must exist in heart [l -31. Labelling studies located a trichloroacetic acidmethanol-precipitable species which .rapidly exchanged units with ATP in rat heart [4], kidney [5] and liver [6]. Selective digestion and chromatography, along with "P-NMR and mass spectrometry studies, led us to propose a structure and the name of oligo-(phosphoglyceroyl-ATP) (PG-ATP), for this compound [7]. In subsequent work we have purified from liver a specific 3'-phosphodiesterase which releases 3-phospho-glyceroyl-ytriphospho(5')adenosine (PG-ATP) units [8] : furthermore in liver and heart, this enzyme is found only in mitochondrial intermembrane space [8] tightly complexed with its substrate [9], suggesting that (PG-ATP), may be exclusively located there too.In perfused rat hearts the acid-insoluble species was observed to reach specific activity equilibrium with [8-I4C]ATP Correspondence to J. Mowbray,

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“…For instance, administration of exogenous ribose accelerates the repletion of ATP and helps maintain its level high in various tissue types [2][3][4]19]. With these tissue-protective effects, ribose has potential therapeutic applications involving the cardiovascular as well as the central and peripheral nervous systems [5,6].…”

Section: Discussionmentioning

confidence: 99%

“…Exogenous ribose has shown beneficial effects in a number of studies. It has been reported to enhance cardiac and muscular performance and to accelerate the repletion of ATP in rat and canine myocardium as well as in isolated cardiomyocytes and endothelial cells [1][2][3][4]. Ribose addition also helps maintain higher levels of ATP in rat heart and dog kidney during transplantation experiments [5], and it led to improvement of neurological symptoms in a patient with adenylosuccinase deficiency [6].…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of human ribokinase and comparison of its properties with E. coli ribokinase and human adenosine kinase

et al. 2007

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Metabolism and salvage of adenine and hypoxanthine by myocytes isolated from mature rat heart

Cited by 31 publications

References 21 publications

Meiotic Induction in Cumulus Cell-Enclosed Mouse Oocytes: Involvement of the Pentose Phosphate Pathway1

Meiotic Induction in Cumulus Cell-Enclosed Mouse Oocytes: Involvement of the Pentose Phosphate Pathway1

Evidence that the recently discovered high‐energy nucleotide derivative, oligo(phosphoglyceroyl‐ATP) forms the end chains of purinogen, a complex polymeric major stroage form of adenine nucleotide and phosphate in heart

Identification and characterization of human ribokinase and comparison of its properties with E. coli ribokinase and human adenosine kinase

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