Gareth D. Jones

Caffeine and other sympathomimetic stimulants: modes of action and effects on sports performance

Stimulants, illegal and legal, continue to be used in competitive sport. The evidence for the ergogenic properties of the most potent stimulants, amphetamines, cocaine and ephedrine, is mostly insubstantial. Low doses of amphetamines may aid performance where effects of fatigue adversely affect higher psychomotor activity. Pseudoephedrine, at high doses, has been suggested to improve high intensity and endurance exercise but phenylpropanolamine has not been proven to be ergogenic. Only caffeine has substantial experimental backing for being ergogenic in exercise. The mode of action of these stimulants centres on their ability to cause persistence of catecholamine neurotransmitters, with the exception of caffeine which is an adenosine receptor antagonist. By these actions, the stimulants are able to influence the activity of neuronal control pathways in the central (and peripheral) nervous system. Rodent models suggest that amphetamines and cocaine interact with different pathways to that affected by caffeine. Caffeine has a variety of pharmacological effects but its affinity for adenosine receptors is comparable with the levels expected to exist in the body after moderate caffeine intake, thus making adenosine receptor blockade the favoured mode of ergogenic action. However, alternative modes of action to account for the ergogenic properties of caffeine have been supported in the literature. Biochemical mechanisms that are consistent with more recent research findings, involving proteins such as DARPP-32 (dopamine and cAMP-regulated phosphoprotein), are helping to rationalize the molecular details of stimulant action in the central nervous system.

Spectroscopic identification of the haem ligands of cellobiose oxidase

A spectroscopic study of the flavocytochrome b enzyme, cellobiose oxidase, employing optical, NMR, EPR and near infra‐red MCD techniques, has identified the axial ligands of the b‐type haem. These are a histidine and a methionine, and this ligation set is discussed in relation to the functional role of the haem group.

Labeling of the Electron Entry Site of Cytochrome c Oxidase Using 51Cr2

51Cr2+ has been used as a probe to locate the electron entry site of bovine cytochrome c oxidase. The results of static titrations, column chromatography, and low pH LDS polyacrylamide gradient gel electrophoresis are reported. Of the protein subunits of cytochrome c oxidase, only subunit II is specifically labeled during electron transfer from Cr2+ to the electron accepting site. We therefore conclude that this site is located in subunit II. Our results provide experimental evidence to corroborate the view that this subunit is associated with redox centers of the enzyme, an hypothesis based on indirect evidence provided by the amino acid sequences and analogy with the bacterial enzyme.

A comparison of the reactions of cytochrome c oxidase, cytochrome c and azurin with Cr2+ ions.

The reduction of cytochrome c oxidase (EC 1.9.3.1) by Cr2+ ions has been studied by stopped-flow spectrophotometry and is compared with the Cr2+ reduction of cytochrome c and azurin. The effects of temperature, pH, and added anions (e.g., SCN-) have been investigated. The behavior of the electron acceptor site of cytochrome c oxidase stands in contrast to that of the other redox proteins with regard to the effects of added anions and we suggest that this reflects the more buried nature of this site in the complex enzyme.