Postsynthetic variants of creatine kinase MM

MYocardial CK-MM has been found to undergo postsynthetic modification after AMI. Studies by isoelectric focusing of normal heart extracts, serial serum samples from patients with AMI, normal sera, and sera from patients with DMD revealed the presence of four variants, designated MM-I, MM-II, MM-III and MM-IV, at pH values 6.90, 6.62, 6.36, and 6.20, respectively. The MM variants, together with two MB variants, could also be demonstrated by electrophoresis on cellulose acetate. Heart extract contained primarily MM-I. Serum samples obtained early after infarction (9 to 12 hr) showed predominantly MM-I, MM-II, and MM-III. With increase in time after infarction (24 to 96 hr), there was a gradual shift in which MM-I and MM-II decreased while MM-III and MM-IV increased. These results could be mimicked by incubating an extract of human heart with normal serum for increasing time intervals. Normal serum and serum from DMD patients--both of which contain steady-state levels of MM isoenzyme activity--showed all four variants. There was, however, a preponderance of MM-I and MM-II in normal serum, whereas serum from DMD patients showed a preponderance of MM-II and MM-III. We conclude that the process of postsynthetic modification after AMI probably starts at the site of injury in the myocardium because the variants can be demonstrated in the serum within a few hours after infarction. Further modification then occurs in the circulation after enzyme release from the site of injury has ceased. These data suggest that analysis of CK variants may provide a unique means of assessing the time of onset of necrosis in AMI and may have potential for detecting reinfarction and for monitoring the duration of enzyme release from the site of injury.