Isoenzymes and isoforms of CK: what is the score?

The report by Williams et al. (1) on assays of creatine kinase (CK; EC 2.7.3.2) isoenzymes and isoforms by isoelec-ti-ic focusing shows us that the isoforms of CK may be more numerous than we realized. We are familiar with three isoenzymes for CK, and three isoforms have been described for CK-MM (2), and two for CK-MB (3). This plethora of isoforms (labeled 1, 2, 3 and a to k) probably is a consequence of the excellent resolution of CK species with small size and (or) charge differences achieved by Williams et al. (1). I suggest that, with even more discrete separation techniques, additional CK isoforms will be described. Once released into the peripheral blood, CK loses terminal amino acids by the action of carboxypeptidase-N present normally in blood, yielding enzymatically active fragments. Also, it is likely that there are catalytically inactive CK protein fragments that we miss but that are present in the blood of both well and sick. As metabolism proceeds, CK isoforms appear with decreasing molecular masses and faster anodic mobility. An important issue is whether these isoform bands have any clinical significance or are simply laboratory curiosities. By isoelectric focusing techniques, Williams et al. (1) describe CK-a and CK-b isoforms in 4% and 26%, respectively, of patients with acute myocardial infarction (AMI); these isoforms were not observed in any of 19 patients without AM!. Thus the CK-a and CK-b isoforms are interesting, but owing to their inconsistent appearance are really of little help in discriminating between patients with and without AM!. CK-a may be mitochondrial CK, an isoenzyme portending a bad outcome. What must be remembered is that the diagnosis of AMI can never be made on the basis of laboratory data alone; certainly, CK-MB has become a key test in this diagnosis, but the test is fallible (4, 5). Also, there are patients with symptoms suggesting AM! but who have equivocal laboratory and other information; a diagnosis of AM! is possible but is not made; rather, terms like " acute coronary syndrome " or " intermediate syndrome " are used. The isoforms patterns in their (1) post-triathalon athletes look like those in their non-AM! patients, which is reassuring. However, a non-athlete presenting to the emergency room with a CK-MB of 8.9% is certainly not " normal. " Unfortunately, the authors do not give CK isoform data on normal, non-exercising individuals. Williams et al. (1) suggest that …