Blood plasma pyruvate kinase as a marker of muscular dystrophy. Properties in dystrophic chickens and hamsters

Abstract

Pyruvate kinase activity rises sharply in the blood plasma of the genetically dystrophic chicken, and parallels in its timecourse during the development of the disease the appearance of other known signs. The increase in the dystrophic chicken reaches about 30-fold the normal value; in the genetically dystrophic hamster, a similar rise occurs and reaches 20-fold the normal level. A high correlation exists between the plasma pyruvate kinase and creatine phosphokinase activities in the development of dystrophy. The former appeared in the blood rather faster than the latter, despite the threefold greater molecular size of the former. Chickens heterozygous for muscular dystrophy also had plasma pyruvate kinase elevations, which were much smaller than in the homozygotes, but nevertheless significant: the values were about twofold those of the corresponding normal birds. The isoenzymes of pyruvate kinase were quantitatively analyzed by an isoelectric focusing method: dystrophic chicken muscle contains two isoenzymes, the major one being the M 1 form. It was shown thus that the isoenzymes of normal and of dystrophic chicken muscle were indistinguishable. The pyruvate kinase isoenzyme pattern in the chicken erythrocyte was established, and this, also, was identical in dystrophic and normal animals. The pyruvate kinase accumulating abnormally in the dystrophic blood was not the red cell enzyme but, by the isoelectric focusing evidence, was entirely due to enzyme escaping, unchanged, from the skeletal muscle. All our observations showed plasma pyruvate kinase to be an indicator of muscular dystrophy in these animals, and hence likely to be of value as one of the criteria for assessment of chemotherapeutic effects.