IMP REAMINATION TO AMP IN RAT SKELETAL-MUSCLE FIBER TYPES

Inosine 5'-monophosphate (IMP) reamination in skeletal muscle fiber se ctions of the rat hindlimb was studied. High IMP concentrations were e stablished during ischemic contractions in each fiber section: 3.1, 2. 8, or 0.6 mu mol/g in the fast-twitch white (FTW), fast-twitch red (FT R), and slow-twitch red (STR) muscle sections, respectively. Thereafte r blood flow was restored and stimulation was discontinued to allow re amination of IMP. After 0, 2, 5, 10, 15, or 20 min of recovery, muscle sections were freeze-clamped and analyzed for metabolite contents. IM P was nearly fully reaminated after 10 and 20 min of recovery in STR a nd FTR muscles, respectively. Reamination in FTW fibers was delayed an d slower, with only 50% of the IMP reaminated after 20 min of recovery . Significant recovery (similar to 75%) of phosphocreatine occurs in e ach fiber section before the onset of reamination. Reamination was als o evaluated after high-speed treadmill running with or without inhibit ion of reamination by hadacidin. Running resulted in large accumulatio ns of IMP in FTW and FTR fibers (3.5 and 1.4 mu mol/g, respectively); IMP in FTR fibers was higher with hadacidin treatment. Reamination aft er running was much greater in FTR than in FTW fibers and was associat ed with recovery of phosphocreatine. After running, the purine degrada tion products inosine and hypoxanthine were increased in FTW and FTR f ibers in normal and hadacidin-treated animals. Plasma inosine, hypoxan thine, and urate increased after exercise; concentrations continued to increase if reamination was inhibited by hadacidin. These results dem onstrate that when muscle IMP is increased, subsequent degradation and loss of purines occur. Rapid reamination should minimize the quantity of purine lost from muscle and limit the metabolic cost of replenishi ng purines by the de novo synthesis or salvage pathways.