The creatine kinase reaction: a simple reaction with functional complexity |
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Authors: | Kent Sahlin Roger C Harris |
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Institution: | 1.?strand Laboratory, GIH, The Swedish School of Sport and Health Sciences, Department of Physiology and Pharmacology, Karolinska Institutet,Stockholm,Sweden;2.Junipa Ltd,Suffolk,UK |
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Abstract: | The classical role of PCr is seen as a reservoir of high-energy phosphates defending cellular ATP levels under anaerobic conditions,
high rates of energy transfer or rapid fluctuations in energy requirement. Although the high concentration of PCr in glycolytic
fast-twitch fibers supports the role of PCr as a buffer of ATP, the primary importance of the creatine kinase (CK) reaction
may in fact be to counteract large increases in ADP, which could otherwise inhibit cellular ATPase-mediated systems. A primary
role for CK in the maintenance of ADP homeostasis may explain why, in many conditions, there is an inverse relationship between
PCr and muscle contractility but not between ATP and muscle contractility. The high rate of ATP hydrolysis during muscle contraction
combined with restricted diffusion of ADP suggests that ADP concentration increases transiently during the contraction phase
(ADP spikes) and that these are synchronized with the contraction. The presence of CK, structurally bound in close vicinity
to the sites of ATP utilization, will reduce the amplitude and duration of the ADP spikes through PCr-mediated phosphotransfer.
When PCr is reduced, the efficiency of CK as an ATP buffer will be reduced and the changes in ADP will become more prominent.
The presence of ADP spikes is supported by the finding that other processes known to be activated by ADP (i.e. AMP deamination
and glycolysis) are stimulated during exercise but not during anoxia, despite the same low global energy state. Breakdown
of PCr is driven by increases in ADP above that depicted by the CK equilibrium and the current method to calculate ADPfree
from the CK reaction in a contracting muscle is therefore questionable. |
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