title: Creatine kinase as an intracellular regulator.
abstract: Several recent studies have demonstrated the presence of creatine kinase and of phosphorylcreatine in a variety of cells besides striated muscle and brain cells. The total creatine kinase and phosphagen levels in these cells encompass a wide range of values. The available data are collected in this article to demonstrate that the variation of the enzyme and phosphagen concentrations is not random but that the two are interrelated. With both the major isoenzymes of creatine kinase, namely the muscle type and the brain type, the basal levels of phosphorylcreatine follow closely the cellular creatine kinase levels. A hypothesis is presented in which the enzyme itself is the major determinant of phosphorylcreatine content by virtue of its ability to act as an intracellular binding protein for creatine derived from extracellular fluid, and also for cellular ADP. The proposed mechanism further predicts that in cells that contain high levels of actin and thus sequester the cytoplasmic free ADP (e.g. most muscle cells), a high level of creatine kinase can effectively regulate the myokinase reaction by its ability to bind ADP. The net effect of such regulation is to conserve the adenine nucleotide pools in the cell. The evolutionary advantage of these two regulatory functions of creatine kinase in terms of energy conservation is discussed.
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003401:Creatine / Q000502:physiology; D003402:Creatine Kinase / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010725:Phosphocreatine / Q000502:physiology
chemical_list: D007527:Isoenzymes; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D000263:Adenylate Kinase; D003401:Creatine