Development of a refractory stage in a dog model for phenylketonuria

Dogs were fed a continuous diet of phenylalanine (Phe) daily and para-chloro-phenylalanine (p-CPhe), an inhibitor of phenylalanine hydroxylase (PH-ase) every second day. It was reported that such a diet produces a sustained hyperphenylalanemia in rats. We have found, however, that in dogs an initial rise in circulating Phe is followed, after a period of time, by a return to normal levels in spite of diet maintenance. PH-ase ws measured in liver samples obtained from dogs before the start of the above diet and at the time when Phe levels returned to normal. It was found that the post-feeding liver sample had 57%-100% less activity than the normal sample. Accordingly, decline in Phe levels cannot be attributed to an increase in PH-ase activity. Experiments are being initiated using labelled Phe, to investigate whether chronic feeding of Phe and p-CPhe resulted in an intestinal block to Phe absorption, which may explain our experimental findings.