The Creatine-Creatine Phosphate Shuttle for Energy Transport — Compartmentation of Creatine Phosphokinase in Muscle
There are two viewpoints regarding the role of the enzyme creatine Phosphokinase (CPK), which catalyzes the reversible transphosphorylation of creatine and adenine nucleotides in energy transport. The classical viewpoint (Fig. 1) regards CPK as a near equilibrium enzyme buffering cytosolic changes in nucleotide concentration (1,2), with creatine phosphate representing a reservoir of high energy phosphate equivalents (3) and with regulation of energy production relegated to the adenine nucleotides whether in the form of energy charge (4), adenylate phosphate potential (5,6), or ATP/ADP ratio (7). The second viewpoint places CPK and its products, creatine and creatine phosphate, in the central role of energy transport (8–11). The evidence for the latter viewpoint has come about from several diverse lines of reasoning (reviewed in 9). Jacobs et al discovered a distinct isoenzyme of CPK bound to mitochondria in 1964 (12). The significance of this mitochondrial bound form of CPK was studied by Bessman and Fonyo (13) in pigeon breast mitochondria where the possibility of feedback regulation of respiration through production of acceptor creatine was suggested, in accordance with Bessman’s earlier observation on the insulin-like effect of exercise in diabetics (14).
KeywordsCreatine Kinase Adenine Nucleotide Energy Transport Creatine Phosphokinase Heart Mitochondrion
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