Xanthine

About: Xanthine is a research topic. Over the lifetime, 4046 publications have been published within this topic receiving 129820 citations. The topic is also known as: Xanthine.

Purine control of mouse oocyte maturation: evidence that nonmetabolized hypoxanthine maintains meiotic arrest.

Abstract: Hypoxanthine is present in preparations of follicular fluid and has been shown to suppress the spontaneous meiotic maturation of mammalian oocytes in vitro. The present experiments examined the possible role of hypoxanthine metabolism in mediating this meiotic arrest. Four putative inhibitors of the enzyme, hypoxanthine phosphoribosyltransferase (HPRT), which metabolizes hypoxanthine to inosine monophosphate, were tested on lysates of oocyte-cumulus cell complexes. At a concentration of 1 mM, 6-mercapto-9-(tetrahydro-2-furyl)-purine (MPTF) and 6-mercaptopurine (6-MP) suppressed enzymatic activity by 86% and 98%, respectively, while 6-azauridine and 2,6-bis-(hydroxyamino)-9-beta-D-ribofuranosyl-purine had no effect. MPTF and 6-MP increased the inhibitory effect of hypoxanthine on germinal vesicle breakdown, but the other agents did not. The 2 active agents had similar effects on salvage activity and hypoxanthine-maintained meiotic arrest in denuded oocytes. Also, oocytes from XO mice were more sensitive to the meiosis-arresting action of hypoxanthine than oocytes from XX littermates, which have twice the HPRT activity. The actions of the HPRT inhibitors were not due to their conversion to nucleotides via HPRT and negative feedback on purine de novo synthesis, because azaserine and 6-methylmercaptopurine riboside, which are more potent inhibitors of de novo synthesis, had a stimulatory, rather than inhibitory, effect on hypoxanthine-arrested oocytes. Furthermore, several lines of evidence indicate that metabolism of hypoxanthine to xanthine and uric acid by xanthine oxidase does not mediate the inhibitory action of this purine base on meiotic maturation. The data therefore suggest that nonmetabolized hypoxanthine is responsible for the meiotic arrest observed, most likely through suppression of cAMP degradation.

Electrochemical Oxidation of Uric Acid and Xanthine at the Pyrolytic Graphite Electrode Mechanistic Interpretation of Electrochemistry

Abstract: The quantitative course of electrochemical oxidation of uric acid and xanthine at the pyrolytic graphite electrode has been examined between pH 1–7, the most commonly encountered pH range in biological systems. Basically, uric acid is oxidized in a primary oxidation of the bond to give a readily reducible and highly reactive bis‐imine. The bis‐imine can be detected as a cathodic peak by fast sweep cyclic voltammetry. Complete hydration of the bis‐imine gives rise to uric acid‐4,5‐diol that breaks down to alloxan and urea at pH 1, allantoin and a small amount of urea at pH 7, and at intermediate pH values mixtures of alloxan, allantoin, urea, and occasionally traces of parabanic acid are formed. Xanthine undergoes a oxidation that proceeds by two stages. The first involves oxidation of the bond to give uric acid which, being more easily oxidized than xanthine, is immediately further oxidized to the uric acid bisimine. This then hydrates and fragments in essentially the same way as described for uric acid, the same products being observed. Mechanisms are developed which explain the observed electrochemistry and over‐all formation of products from this reaction. The nature and yields of products formed electrochemically and the effect of pH on the reaction parallels the biological (enzymatic) oxidation of these compounds.

Advances in the management of malignancy-associated hyperuricaemia.

Abstract: Acute tumour lysis syndrome (ATLS) is a metabolic derangement (hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia) associated with lymphoproliferative malignancies. The nature and severity of the metabolic alterations are variable. Major complications are oliguric acute renal failure and delays in initiating chemotherapy. Current management of ATLS includes hydration, alkalinization, diuretics, when indicated, and the reduction of uric acid levels using allopurinol or urate oxidase. Allopurinol inhibits xanthine oxidase, an enzyme that catalyses the conversion of hypoxanthine and xanthine to uric acid. Urate oxidase (Uricozyme), a naturally occurring proteolytic enzyme in many mammals, degrades uric acid to allantoins, which are ten times more soluble than uric acid and easily eliminated by the kidneys. Recently, Sanofi Research isolated a recombinant urate oxidase (SR29142) as a cDNA clone from Aspergillus flavus, expressed in the yeast strain Saccharomyces cerevisiae. Preclinical studies have documented its biological effects as a urolytic enzyme. Twenty-eight healthy male volunteers received SR29142, and a rapid decline of uric acid below measurable levels was seen within 4 h in all patients receiving a dose of more than 0.10 mg kg(-1). Currently, SR29142 is undergoing clinical studies in both Europe and the USA in patients with acute leukaemias or B-cell non-Hodgkin's lymphoma to demonstrate its efficacy and safety in this population of patients at highest risk of developing ATLS or its life-threatening sequelae.