Creatine metabolism in the pyridoxine-deficient rat

Creatine metabolism was studied in rats fed a pyridoxine-deficient diet for 6-7 wk. Indirect evidence had suggested that creatine levels may be low in these animals, since their livers accumulate a competitive inhibitor of creatine biosynthesis (S-adenosylhomocysteine), and they develop muscle signs suggestive of abnormal creatine metabolism. In contrast, however, the concentration of creatine in both liver and skeletal muscle of pyridoxine-deficient rats was higher than in pair-fed control rats. Pair-fed control rats also had higher creatine levels in liver and skeletal muscle than ad libitum-fed control rats, whose feed intake was about double that of the pair-fed control rats. Thus, feed restriction also increased the tissue creatine levels, and this effect was augmented slightly by pyridoxine deficiency. These changes could not be explained by the results of in vitro measurement of the enzymes of creatine biosynthesis. The activity of guanidoacetate methyltransferase in liver did not differ significantly among the three groups of animals. Kidney arginine-glycine transamidinase activity was noticeably lower in the pyridoxine-deficient rats than in pair-fed control rats and lower in pair-fed control rats than in ad libitum-fed control rats. Since creatinine excretion did not differ significantly among the three animal groups, the results suggest that decreased turnover of creatine may occur during pyridoxine deficiency above and beyond that of an apparent feed restriction alone.