Phenylalanine Phenylalanine hydroxylase Tyrosine Tyrosine aminotransferase 4-Hyd
ID: 141014 • Letter: P
Question
Phenylalanine Phenylalanine hydroxylase Tyrosine Tyrosine aminotransferase 4-Hydroxyphenylpyruvic acid 4-hydroxyphenylpyruvic acid dioxygenase Nitisinone) Homogentisic acid Homogentisate 1,2-dioxygenase ALKAPTONURIA Maleylacetoacetic acid Succinylacetoacetic acid Fumarylacetoacetic acid Fumarylacetoacetic acid hydrolase TYROSINEMIA TYPEI Succinylacetone Fumaric acid+Acetoacetic acid Tyrosinemia Type I is caused by deficiency in the enzyme FAH (fumarylactoacetate hydrolyase). What compounds will accumulate in the absence of this enzyme? Please explain why (briefly) The occumulation of ulation of these compounds leads to liver failure and/or liver cancer, sometimes very early in Accum life. One effective treatment uses the compound, Nitisinone. Nitisinone inhibits the reaction shown, that catalyzed by 4-hydroxyphenylpyruvis acid dehydrogenase (abbreviated HPPD). Why might this be an effective treatment ?Explanation / Answer
Hi,
Here the pathway of utilization of the amino acid phenylalanine is illustrated. In the absence of the enzyme Fumarylacetoacetic acid hydrolase, the Formation of Fumaric acid and Acetoacetic acid is inhibited ( it is called Tyrosinemia Type I disease). This increases the flux of Fumarylacetoacetic acid initially. However, as given in the pathway, this compound is not static and is converted into Succinylacetoacitic acid. This, in turn, will form Succinylacetone. Hence Succinylacetone will accumulate in the Tyrosinemia type I disease.
The treatment using Nitisinone can inhibit the reaction catalysed by HPPD. This inhibits all downstream conversion of 4-hydroxyphenylpyruvate acid. No further metabolites such as fumaric acid or succinylacetone are produced. Hence it can be an effective treatment.