The inhibitory effect of actinomycin D and cycloheximide on the increase in activity of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in experimentally induced diseased skeletal muscles.

The myotoxic effect of the subcutaneous administration of N,N1-dimethyl-p-phenylenediamine (DPPD) in rats was enhanced by the simultaneous administration of hyaluronidase. The resulting myopathy was associated with an early and dramatic increase in activity of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Administration of actinomycin D or cycloheximide prior to the combined DPPD and hyaluronidase treatment prevented the increase in activity of both pentose phosphate pathway enzymes, indicating that the increase in activity requires RNA synthesis and protein synthesis. The possibility that the increase in activity of both NADPH-regenerating enzymes results from the modification by effectors of existing less active forms of these enzymes leading to more highly active forms was refuted.