Abstract

Alkaptonuria is a rare metabolic disorder characterized by the deficiency of homogentisate 1,2-dioxygenase, leading to the accumulation of homogentisic acid (HGA) derived from tyrosine metabolism. Nitisinone, an inhibitor of 4-hydroxyphenylpyruvate dioxygenase, is commonly used in the management of alkaptonuria to reduce the production of HGA. However, the impact of nitisinone on the phenylalanine/tyrosine pathway dynamics in alkaptonuria remains unclear. In this study, we investigated the fluctuations in the phenylalanine/tyrosine pathway under nitisinone treatment in alkaptonuria patients. Plasma levels of phenylalanine, tyrosine, and related metabolites were monitored over a specified treatment period. Additionally, enzyme activities involved in phenylalanine and tyrosine metabolism were assessed. Our findings reveal significant alterations in the phenylalanine/tyrosine pathway dynamics in response to nitisinone therapy, suggesting potential implications for the management and understanding of alkaptonuria pathophysiology.