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Regulation of Skeletal Muscle Reactive Oxygen Species During Exercise
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Catherine A. Bellissimo, Christopher G.R. Perry
Xanthine oxidase (XO): XO is active in muscle endothelial cells and leucocytes (46, 54, 141). XO regulates catabolism of hypoxanthine to xanthine and xanthine to uric acid, with superoxide being produced in both cases. Hypoxanthine is a product of adenine nucleotide degradation, such that decreases in ATP during intense exercise have been linked to hypoxanthine release from muscle during and more so after intense exercise (52, 53, 55). This greater release suggests that exercise increases flux through XO, which might implicate this enzyme as a unique source of superoxide during exercise. However, there is limited direct evidence of XO-derived ROS in muscle to support this notion. One report suggested that inhibition of XO with allopurinol prevented plasma markers of muscle damage (creatine kinase, aspartate aminotransferase) in four Tour de France cyclists compared to five control cyclists (42). Given circulating creatine kinase (CK) is a marker of muscle damage, this finding suggests that muscle XO might contribute to exhaustive exercise-induced damage. This is supported by reductions in circulating CK in mice with allopurinol during exhaustive exercise along with faster restoration of glutathione (GSH) post-exercise, which indirectly suggests attenuated ROS production in muscle (26). However, no direct measures of muscle XO activity were reported.
Purine nucleoside phosphorylase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Deficiency of PNP is unique among immunodeficiencies in that patients have impressive hypouricemia [9, 10] and a very low level of excretion of uric acid in the urine. These features provide a diagnostic marker for the disease [11]. Concentrations of inosine and guanosine in the serum are markedly elevated, as is their excretion in the urine [3, 12]. These patients overproduce purines de novo, which appears to be a consequence of the accumulation in cells of PRPP [6]. These observations suggest a role for purine nucleoside phosphorylase in providing a source of hypoxanthine for nucleotide synthesis catalyzed by hypoxanthine guanine phosphoribosyl transferase (HPRT). In the absence of substrate hypoxanthine or in the absence of HPRT, levels of PRPP rise.
Fever In Inherited and Metabolic Disorders
Published in Benedict Isaac, Serge Kernbaum, Michael Burke, Unexplained Fever, 2019
Primary gout may be caused by inborn errors of urate metabolism. In the majority of patients, the exact biochemical abnormality has not been yet elucidated, but a polygenic propensity to urate overproduction (in 85% of cases) or reduced fractional renal urate excretion (in 10 to 15% of patients) may be demonstrated. In rare instances specific enzyme defects have been demonstrated, such as the sex-linked partial deficiency of hypoxanthine-guanine phopsphoribosyl transferase deficiency.27
Purine metabolites can indicate diabetes progression
Published in Archives of Physiology and Biochemistry, 2022
Yogaraje Gowda C. Varadaiah, Senthilkumar Sivanesan, Shivananda B. Nayak, Kashinath R. Thirumalarao
Uric acid has some physiologic functions including stimulation of the rennin-angiotensin system and through its actions on endothelial cells and vascular smooth muscle cells (Paravicini and Touyz 2008). These functions are all related to the incidence and progression of diabetic complications (Aastha et al. 2016). Moreover, protein glycation in diabetes may lead to muscle wasting and increased release of purine, which acts as the main source of uric acid formation (Anwar and Meki 2003).In the present study, we observed positive association between increased levels of xanthine-to-hypoxanthine ratio with diabetes complications. We observed an association between elevated plasma and liver AMP levels with a higher diabetes risk which is very much similar to the previous research work published recently (Papandreou et al. 2019).
Current understanding of Lesch-Nyhan disease and potential therapeutic targets
Published in Expert Opinion on Orphan Drugs, 2019
In 1964 M Lesch and W Nyhan reported the case of two brothers with a disorder of uric acid metabolism and neurological dysfunction [1]. Three years later, Seegmiller, Rosenbloom, and Kelly [2] reported the complete deficiency of the activity of the purine metabolism enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) as the cause of the Lesch–Nyhan disease (LND) (OMIM 300,322). The same year, a partial deficiency of HPRT activity associated with gout and no neurological involvement was described and termed Kelly–Seegmiller syndrome or HPRT-related gout [3] (OMIM 300,323). Nowadays, it is considered that a continuous spectrum of neurological involvement is present in HPRT-deficient patients [4–6] and the term Lesch–Nyhan variant has been introduced to include patients with HPRT-related gout and a variable degree of neurological involvement, but without the complete LND. The prevalence of the disease is estimated to be 1/380,000 live births in Canada [7], and about 1/500.000 live births in UK for LND patients [8]; and 1/235,000 live births for all HPRT-deficient patients in Spain [9] and the disease has been described in all races.
Molecular structure investigation towards pharmacodynamic activity and QSAR analysis on hypoxanthine using experimental and computational tools
Published in Egyptian Journal of Basic and Applied Sciences, 2018
G. Susithra, S. Ramalingam, S. Periandy, R. Aarthi
The Hypoxanthine is normally belongs to heterocycles family which peculiarly contains pyrimidine and imidazole rings. Hypoxanthine is a purine derivative with nitrogenous base rarely found as a constituent nucleic acid [1]. Heterocycles showing in their strange structures where the pyrimidine ring is fused to azolic moieties, are interesting systems being with important biochemical, pharmacological and physicochemical property [2,3] . During the recent decades numerous pyrimidine derivatives have found to have wide clinical and pharmacological applications [4]. Particularly, fused pyrimidine with Imidazole ring persists to attract considerable attention since their great practical usefulness, primarily due to very wide spectrum of biological activities [5,6] . The hypoxanthine naturally has different Tautomerism which resolves the specific prototype of hydrogen bond donors and acceptors present in a specific molecule. Similarly, the fused imidazole and its derivatives are generally having bioactivity against inflammatory mediators [7].