ENERGETIC STATUS AND MITOCHONDRIAL OXIDATIVE CAPACITY OF RAT SKELETAL-MUSCLE IN RESPONSE TO CREATINE ANALOG INGESTION

A creatine analogue, beta-guanidinopropionic acid (beta-GPA), was admi nistered in the food (1% w/w) of 8 male rats for 6 weeks, while 8 cont rol rats received a standard diet. Mitochondrial oxidative capacity an d cytosolic modulators of mitochondrial oxidative phosphorylation (fre e ADP, ATP-to-free ADP ratio) were evaluated in the soleus and extenso r digitorum longus (EDL) muscles. Mitochondrial adaptation to the diet was significantly different between muscles. Citrate synthase activit y and mitochondrial ATP synthesis rate were 35 and 45% higher in EDL m uscle, respectively, whereas they were virtually unchanged in the sole us muscle. In both muscles, 3-hydroxyacyl-CoA dehydrogenase activity r emained unaffected. Regardless of muscle type, creatine, phosphocreati ne and ATP concentrations, as well as the total adenine nucleotide con tent (ATP + ADP + AMP), were significantly lower in beta-GPA fed rats. Whereas free ADP concentration remained unchanged, a significantly gr eater decrease in ATP-to-free ADP ratio was observed in EDL than in th e soleus muscle. It is suggested that regulation of mitochondrial oxid ative phosphorylation, through changes in metabolite concentrations, c ould be an important factor to consider for mitochondrial adaptation i nduced by beta-GPA feeding.