A premature infant is found to have tyrosinemia type I. A 4-week course of NTBC (nitisinone) is initiated. NTBC inhibits which enzyme, and thereby prevents accumulation of which directly toxic metabolite?

• A Fumarylacetoacetase; prevents fumarylacetoacetate accumulation
• B Tyrosine aminotransferase; prevents homogentisate accumulation
• C Maleylacetoacetate isomerase; prevents methylmalonate accumulation
• D 4-hydroxyphenylpyruvate dioxygenase; prevents succinylacetone accumulation ✓

Explanation

Tyrosinemia type I results from fumarylacetoacetase deficiency, causing accumulation of fumarylacetoacetate and maleylacetoacetate, which spontaneously convert to succinylacetone. Succinylacetone inhibits delta-aminolevulinic acid dehydratase (causing porphyria-like crises) and is directly hepatotoxic and nephrotoxic. NTBC inhibits 4-hydroxyphenylpyruvate dioxygenase, an enzyme upstream of the block, preventing formation of all downstream toxic metabolites including succinylacetone. This is the primary treatment strategy along with dietary tyrosine/phenylalanine restriction.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.