Ti

ATP ADP

Cytosol g

Outer Mitochondrial Membrane

Transferases

Inner Mitochondrial Membrane

i atp i

Mitochondria

FIGURE 9.2 Basic diagram of the creatine phosphate shuttle.

CK activity, containing large amounts of MM-CK, than slow-twitch oxidative fibers, but the latter have a higher percentage of Mi-CK.32-35 Recent studies suggest that dietary and muscle availability of creatine may influence CK activity in various healthy and diseased populations.203136-41

From an ergogenic viewpoint, resynthesis of PCr could be the critical factor during sustained very high intensity exercise. Although the mechanisms are not clearly understood, a creatine phosphate shuttle may be the functional mechanism.3442 In addition to its role as an energy buffer, it has been proposed that the CK-PCr system functions in energy transport on the basis of the functional and physical association of CK isoenzymes with subcellular sites of ATP production and hydrolysis. In the creatine phosphate shuttle concept, PCr and Cr act as shuttle molecules between these sites.35 One proposed shuttle is believed to be functionally coupled to glycolysis,35 but others believe that the rapid resynthesis of PCr is likely to be oxidative in origin.324344 Mi-CK promotes the formation of PCr from creatine and from ATP formed via oxidative metabolism in the mitochon-dria.34 van Deursen and others35 note that PCr is presumed to diffuse from the mitochondria to the myofibrillar M-band, where it locally serves to replenish ATP with MM-CK as a catalyzing agent. Finally, Cr diffuses back to sites of ATP synthesis for rephospho-rylation. The potential role of modulating CK activity and the shuttling of adenine nucleotides for synthesis and use have prompted a significant amount of research evaluating the potential clinical uses of creatine, as described in the following. Additionally,

since creatine appears to play a role in shuttling of ATP from the mitochondria to the cytosol, it may also be involved in enhancing high-intensity aerobic exercise capacity.3134 Finally, creatine has been shown to have an important role in maintaining brain function and protecting neural activity in the brain following injury.4145-47

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