CREATINE ANALOG BETA-GUANIDINOPROPIONIC ACID ALTERS SKELETAL-MUSCLE AMP-DEAMINASE ACTIVITY

Dietary supplementation of the creatine analogue beta-guanidinopropion ic acid (beta-CTPA) decreases in vitro skeletal muscle AMP deaminase ( AMP-D) activity in rats. Downregulation of AMP-D activity was progress ive and greater in fast-twitch muscles (70-80%) than in the slow-twitc h soleus muscle (similar to 50%). The loss in AMP-D activity had littl e effect on inosine 5'-monophosphate accumulation in mixed-fiber muscl e with intense tetanic contractions. In contrast, inosine 5'-monophosp hate formation was evident earlier in fast-twitch red and white fiber sections of creatine-depleted animals during intense twitch contractio ns, indicating that fast-twitch muscle of beta-GPA-treated rats buffer s decreases in the ATP/ADP(free) ratio via deamination, even though AM P-D activity is less. Isoforms of skeletal muscle AMP-D mRNAs in mixed -fiber muscle were not altered by feeding beta-GPA for up to 9 wk. Cre atine depletion did not alter total immunoreactivity; however, a redis tribution of AMP-D immunoreactivity from primarily an similar to 80-kD a form toward lower apparent molecular mass species (similar to 60 and similar to 56 kDa) was observed. Posttranslational changes in AMP-D a ppear related to changes in activity.