ABNORMAL GLUTATHIONE CONJUGATION IN PATIENTS WITH TYROSINEMIA TYPE-I

Previous studies have suggested that tyrosinaemia type I may be associ ated with reduced glutathione availability due to conjugation of tyros inaemia-associated reactive intermediates with glutathione. In the pre sent study, the glutathione/glutathione S-transferase system of two ty rosinaemia patients and three healthy controls were characterized by a dministering the racemic sedative drug bromisoval, a probe drug for as sessing glutathione conjugation activity in vivo. Furthermore, concent rations of glutathione and glutathione S-transferase class alpha (GSTA ) isoenzymes as well as the glutathione S-transferase class mu phenoty pe were assessed in the blood of six tyrosinaemia patients. The excret ion of bromisoval mercapturates in healthy children was comparable to that observed in healthy adults. Tyrosinaemia patients were found to h ave a very high urinary recovery of bromisoval mercapturates (greater than or equal to 60% of I:he dose compared to about 30% for healthy, a ge-matched children and adults), which could be attributed mainly to a higher urinary excretion of the mercapturate derived from S-bromisova l. Healthy children and adults predominantly excrete the (R)-bromisova l mercapturate. The differences in amount excreted as well as in stere oselectivity of the urinary excretion of bromisoval mercapturates in t yrosinaemia patients are possibly related to an increased activity of specific glutathione S-transferase isoenzymes. Plasma glutathione and blood cell glutathione disulphide concentrations in tyrosinaemia patie nts were normal. Low blood cell glutathione concentrations were in gen eral found only in two patients with a poor clinical condition. These results indicate that, in contrast to previous suggestions, reduced gl utathione availability is not a generalized problem in (stabilized) ty rosinaemia patients.