title: An aberrant adenylate kinase isoenzyme from the serum of patients with Duchenne muscular dystrophy.
abstract: The sera from patients with human Duchenne (X-linked) progressive muscular dystrophy contain elevated adenylate kinase (ATP: AMP phosphotransferase, EC 2.7.4.3) activities, in addition to their characteristically high creatine kinase (ATP; creatine N-phosphotransferase, EC 2.7.3.2) activities. By agarose gel electrophoresis of human Duchenne dystrophic serum, the presence of an apparently normal human serum adenylate kinase together with a variant species of adenylate kinase was detected. The latter enzyme species appeared, in its mobility, to be similar to that of the normal human liver-type adenylate kinase. The presence of this aberrant liver-type adenylate kinase could also be demonstrated by characteristic (for the liver type) inhibition patterns with P1,P5-di-(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate. On the other hand, by inhibition titrations with an anti-muscle-type adenylate kinase, hemolysates from the erythrocytes of several Duchenne and Becker's dystrophics were found to contain approx. 96% muscle-type adenylate kinase and their serum approx. 97% muscle-type adenylate kinase. These same patients contained approx. 89% M-M type creatine kinase in their serum (by inhibition against anti-human muscle-type creatine kinase) indicative of the presence also of M-B plus B-B type active isoenzymes. All of these data can best be explained by the presence of a variant or mutant adenylate kinase isoenzyme in the dystrophic serum. This isoenzyme appears to resemble the liver type in its inhibition patterns with P1,P5-di(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate, and in its heat stability (compare also the agarose gel electrophoresis pattern); but structurally, it is a muscle type, or derived from a muscle type, as shown immunologically by inhibition reactions with anti-muscle-type adenylate kinase. Whether this is a fetal-type isoenzyme of adenylate kinase will require further investigation.
mesh_terms: D000227:Adenine Nucleotides / Q000494:pharmacology; D000263:Adenylate Kinase / Q000037:antagonists & inhibitors / Q000097:blood*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015226:Dinucleoside Phosphates; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D005260:Female; D006801:Humans; D007158:Immunologic Techniques; D007527:Isoenzymes / Q000097:blood*; D008099:Liver / Q000201:enzymology*; D008297:Male; D009136:Muscular Dystrophies / Q000201:enzymology / Q000235:genetics*; D010728:Phosphoenolpyruvate / Q000494:pharmacology; D010770:Phosphotransferases / Q000097:blood*; D014960:X Chromosome
chemical_list: D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; D007527:Isoenzymes; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; D010728:Phosphoenolpyruvate; D004228:Dithionitrobenzoic Acid; D010770:Phosphotransferases; D000263:Adenylate Kinase