Enzyme defect in a case of tyrosinemia type I, acute form.

We determined the activities of tyrosine aminotransferase (TAT, EC 2.6.1.5), p-hydroxyphenylpyruvate oxidase (p- HPPA oxidase, EC 1.14.2.2) and fumarylacetoacetate fumarylhydrolase ( FAH , EC 3.7.12) in cytosol of the liver and kidney tissues obtained at autopsy from a case of hereditary tyrosinemia type I. Values were compared with those from a control group of autopsied tissues from three adults and six children, who had died of other causes. In tyrosinemia, these three hepatic enzyme activities were all decreased: TAT showed approximately 35%, p- HPPA oxidase 11%, and FAH 60% of the corresponding control values. On the other hand, kidney enzymes in tyrosinemia revealed that FAH was most significantly decreased to approximately 14% of the control activity. Km values for substrate--determined for p- HPPA oxidase and FAH --were not different between the patient and controls, suggesting no altered properties of these enzymes. We conclude that in the present case of hereditary tyrosinemia type I, the activities of p- HPPA oxidase in liver and FAH in kidney were most strikingly affected. This fact may in part explain the deteriorated metabolism of tyrosine observed in this patient.