Unimpaired energy metabolism in experimental neuropathy induced by p-bromophenylacetylurea.
The contribution of defective energy metabolism to the induction of neuronal pathology by p-bromophenylacetylurea (BPAU) was examined in several ways. It was found that a saturated aqueous solution of BPAU had no effect on the activity of crystalline glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or phosphofructokinase (PFK). In rats with total hindlimb paralysis from treatment with BPAU (400 mg/kg), the endogenous GAPDH and PFK of sciatic nerve showed normal activity. Endogenous enolase and nerve-specific enolase activities were likewise unaffected. Consequently, it appeared improbable that BPAU neuropathy involves impaired glycolysis. This conclusion was supported by the failure to prevent hindlimb weakness by feeding pyruvate, a substrate for the Krebs cycle. To test for interference with glycolysis at other steps, or for an impairment in oxidative phosphorylation, adenosine triphosphate (ATP) and creatine phosphate were measured. The amounts of high energy phosphates in nerves of paralyzed animals were found to be the same as in nerves of untreated and vehicle-treated controls. A similar observation was made in nerves regenerating from a crush injury. To test turnover, ATP and creatine phosphate were measured in nerves exposed to an N2 atmosphere in vitro. Since the high energy phosphates disappeared at the same rates in all groups, it was concluded that BPAU neuropathy does not alter energy utilization. In our view, BPAU neuropathy arises by a mechanism that does not depend on altered energy metabolism.
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D004734:Energy Metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D010525:Peripheral Nerves / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D010725:Phosphocreatine / Q000032:analysis; D010732:Phosphofructokinase-1 / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014508:Urea / Q000031:analogs & derivatives* / Q000633:toxicity
D009419:Nerve Tissue Proteins; D010725:Phosphocreatine; C004506:4-bromophenylacetylurea; D000255:Adenosine Triphosphate; D014508:Urea; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010732:Phosphofructokinase-1; D010751:Phosphopyruvate Hydratase