The metabolism of cinnamic acid by healthy and phenylketonuric adults: a kinetic study.

The enzyme phenylalanine ammonia lyase taken orally has been found to reduce the rise in blood phenylalanine that normally occurs following a protein meal. Therefore the enzyme has a potential use in the management of the genetic disease phenylketonuria. The enzyme mediates the conversion of phenylalanine to cinnamic acid and its possible clinical future has necessitated a more detailed study of the product of its reaction. Cinnamic acid is a compound of low toxicity which is converted in the mammalian body primarily to hippuric acid. We have examined the kinetics of this process in a healthy male and in two patients with untreated phenylketonuria. In addition we have attempted to clarify the inconsistencies in earlier published work about the status of other, minor metabolites. Following an oral load of sodium (2H6) cinnamate there is an increase in urinary hippuric acid largely due to the excretion of (2H5) hippuric acid. In the subjects studied there was no major difference in the rate of elimination although the amount of cinnamic acid converted was less in those with phenylketonuria. This may reflect reduced first-pass absorption by the liver in untreated phenylketonuria enabling increased uptake to occur in other parts of the body.