Caffeine and exercise: metabolism and performance.
ABSTRACT Caffeine ingestion prior to prolonged exercise delays fatigue. However, the mechanisms involved are very unclear. Caffeine is associated with elevated plasma epinephrine but the metabolic impact of this is uncertain. Glycogen sparing occurs in active muscle, at least in the first few minutes, but studies have generally failed to demonstrate enhanced fat metabolism. The demethylation of caffeine by the hepatic cytochrome P-450 oxygenases begins within minutes and dimethylxanthines (especially paraxanthine) are generated. These compounds appear in the plasma within an hour of caffeine ingestion and may have effects on tissues that have been attributed to caffeine and/or epinephrine. While the most widely supported theory is that caffeine and other methylxanthines are adenosine receptor antagonists, this action alone cannot explain all of the observed responses. Nevertheless, habituation to and withdrawal from caffeine are associated with up and down regulation of adenosine receptors. One study demonstrated marked differences in the effects of caffeine on the plasma concentrations of epinephrine and dimethylxanthines between caffeine users and nonusers. Caffeine is clearly a very active drug that has many effects on humans including increasing exercise endurance. This can be associated with muscle glycogen sparing and elevated plasma epinephrine, but the underlying mechanisms are unknown.
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ABSTRACT: Kinetic studies of both liver and muscle phosphorylase a demonstrate that caffeine and glucose inhibit the binding of glucose 1-phosphate to the enzyme in a synergistic competitive and nonexclusive manner. Inhibition studies for numerous other caffeine analogs show that the muscle enzyme has a relaxed specificity for this negative effector. The liver enzyme is more discriminating by preferential binding of methylated oxypurines. Physiological concentrations of AMP and ATP, which affect the enzymic activity at a separate site, prevent glucose from effectively inhibiting the enzyme. The addition of the second synergistic ligand improves the binding of glucose. These data suggest that glucose homeostasis as regulated by phosphorylase may be dependent on a second ligand and that the role of glucose in this physiological process may have been overestimated. A structural rationalization of this synergistic response is discussed with reference to the crystal structure of the muscle enzyme.Journal of Biological Chemistry 01/1979; 253(24):9102-6. · 4.65 Impact Factor
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ABSTRACT: Central stimulant actions of 10 methylxanthines in mice correlate with affinities for adenosine receptors labeled with N6-[3H]cyclohexyladenosine. Affinities of methylxanthines for adenosine receptors are consonant with central levels attained at behaviorally effective doses. The much higher concentrations of methylxanthines required to influence benzodiazepine receptor binding do not correlate with behavioral potency. N6-(L-Phenylisopropyl)adenosine (L-PIA), a metabolically stable analog of adenosine with high affinity for adenosine receptors, is an extremely potent behavioral depressant, reducing locomotor activity of mice at doses as little as 0.05 mumol/kg. The D isomer, which has much less affinity for adenosine receptors, is much less active as a central depressant. Theophylline stimulates locomotor activity and reverses depressant effects of L-PIA. Caffeine or 1,7-dimethylxanthine, when administered alone, elicits biphasic effects, with locomotor depression at lower doses and stimulation at higher doses. When administered with L-PIA, even low doses of caffeine produce marked stimulation. 3-Isobutyl-1-methylxanthine given alone elicits only behavioral depression. However, like theophylline and caffeine, isobutylmethylxanthine reverses the L-PIA-evoked depression, converting it into pronounced locomotor stimulation. The data strongly suggest that the behavioral stimulant effects of methylxanthines involve a blockade of central adenosine receptors.Proceedings of the National Academy of Sciences 06/1981; 78(5):3260-4. · 9.74 Impact Factor
- Metabolism 09/1968; 17(8):702-7. · 3.10 Impact Factor