Purine metabolism during strenuous muscular exercise in man

doi:10.1016/0026-0495(80)90067-0

Metabolism

Volume 29, Issue 3, March 1980, Pages 254-260

https://doi.org/10.1016/0026-0495(80)90067-0 Get rights and content

Abstract

This study was designed to examine the influence of exercise on purine metabolism in man. In 15 men, the plasma uric acid concentration increased from 6.9 to 8.5 mg/dl following a 5000-m race and from 6.2 to 7.9 mg/dl in 11 men following a 42-km marathon. During a progressive exercise test on a cycle ergometer, the plasma uric acid concentration did not change significantly in 11 subjects. However, the plasma oxypurines increased from 19 μM at rest to 50 μM at exhaustion and the urinary excretion of oxypurines increased from 140 to 400 μmol/g creatinine. Intracellular ATP decreased from 5.17 to 2.91 μmol/g and ADP and AMP increased from 0.85 to 1.29 and from 0.12 to 0.15 μmol/g wet weight, respectively. These observations suggest that there is an accelerated degradation of purine nucleotides to the precursors of uric acid in skeletal muscle during vigorous exercise.

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Increased glucose metabolism correlated with TCA cycle constituents (malate, citrate, α-ketoglutarate) and resulted in a marked increase of products of adenine nucleotide catabolism (i.e., hypoxanthine and xanthine) that are markers of ATP turnover (Lewis et al., 2010) (Figure 2B). In addition, we detected a delayed increase of the purine end-product uric acid, presumably due to increased synthesis and decreased renal excretion (Sutton et al., 1980) (Figure S4). Finally, we also detected an increase of coagulation and hemostasis factors, such as von Willebrand factor (vWF) and A disintegrin and metalloprotease with thrombospondin motif repeats 13 (ADAMTS-13), likely in response to the shear stress induced by treadmill exercise (Stakiw et al., 2008).
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Nevertheless, these findings from genetic, epidemiological, clinical, and experimental studies of UA suggest that concentrations of UA in the upper normal range are generally beneficial compared to lower concentrations, whereas higher concentrations that result in crystal formation are detrimental. In response to physical exercise, levels of circulating and skeletal muscle UA increase in humans, as a result of ATP hydrolysis and inhibition of renal clearance of UA (Child et al., 1998; Emmerson et al., 1978; Hellsten-Westing et al., 1994; Sutton et al., 1980). It has been proposed, but not established, that UA plays a role in sustaining muscle function and reducing cellular damage during intense physical exertion (Castejon et al., 2006; Green and Fraser, 1998).
Among mammals, there is a positive correlation between serum uric acid (UA) levels and life span. Humans have high levels of UA because they lack a functional urate oxidase (UOX) enzyme that is present in shorter lived mammals. Here, we show that male and female mice with UOX haploinsufficiency exhibit an age-related elevation of UA levels, and that the life span of female but not male UOX+/− mice is significantly increased compared to wild-type mice. Serum UA levels are elevated in response to treadmill exercise in UOX+/− mice, but not wild-type mice, and the endurance of the UOX+/− mice is significantly greater than wild-type mice. UOX+/− mice exhibit elevated levels of brain-derived neurotrophic factor, reduced brain damage and improved functional outcome in a model of focal ischemic stroke. Levels of oxidative protein nitration and lipid peroxidation are reduced in muscle and brain tissues of UOX+/− mice under conditions of metabolic and oxidative stress (running in the case of muscle and ischemia in the case of the brain), consistent with prior evidence that UA can scavenge peroxynitrite and hydroxyl radical. Our findings reveal roles for UA in life span determination, endurance and adaptive responses to brain injury, and suggest novel approaches for protecting cells against injury and for optimizing physical performance.
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Moreover, lactate and glycerol-3-phosphate, two of the metabolites increased in nicotine-treated fish, are well-known markers of anaerobic metabolism (Harris and Foster, 1990). The increase in ADP, inosine and hypoxantine found in the treated fish is also consistent with the increase in the purine ribonucleotide catabolism described in humans after strenuous muscular exercise (Sutton et al., 1980). Finally, the content of creatine, precursor of the phosphagen phosphocreatine, and its degradation product creatinine, were also enhanced by nicotine treatment.
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^☆: Supported in part by grants from the Medical Research Council of Canada, the Ontario Heart Foundation, and USPHS Grants AM 19674 and 5MO1 RR-42-14.

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Purine metabolism during strenuous muscular exercise in man☆

Abstract

Am J Med

J Biol Chem

J Biol Chem

Lancet

Am J Med

J Biol Chem

Metabolism

Metabolism

Metabolism

Metabolism

Effects of drugs on uric acid in man

Ann Rev Pharmacol

Overproduction of uric acid in hypoxanthine-guanine phosphoribosyltransferase deficiency: Contribution by impaired purine salvage

J Clin Invest

On the origin of endogenous uric acid

Quart J Med

Some changes in the chemical constituents of the blood following a marathon race

JAMA

Influence of muscular exercise on uric acid excretion in man

J Appl Physiol

Simultaneous study of the blood, also gastric and other manifestations resulting from sweating

Am J Physiol

The medical problems of mass participation in athletic competition: The “City-to-Surf” race

Med J Aust