| Step | Enzyme (gene) | Reaction | Disease associated with deficiency | Nitisinone action |
|---|---|---|---|---|
| 1 | Tyrosine aminotransferase (**TAT**) | Tyrosine → 4-hydroxyphenylpyruvate (pqac-00000021, pqac-00000022) | Tyrosinemia type II | No |
| 2 | 4-hydroxyphenylpyruvate dioxygenase (**HPD**) | 4-hydroxyphenylpyruvate → homogentisate (pqac-00000019, pqac-00000022) | Tyrosinemia type III / Hawkinsinuria (pqac-00000012, pqac-00000014) | **Yes — nitisinone inhibits HPD at this step** (pqac-00000019, pqac-00000036) |
| 3 | Homogentisate 1,2-dioxygenase (**HGD**) | Homogentisate → 4-maleylacetoacetate (pqac-00000022, pqac-00000023) | Alkaptonuria | No |
| 4 | Maleylacetoacetate isomerase (**MAI / GSTZ1**) | 4-maleylacetoacetate → 4-fumarylacetoacetate (pqac-00000021, pqac-00000022) | Not specified in the cited pathway sources | No |
| 5 | Fumarylacetoacetate hydrolase (**FAH**) | 4-fumarylacetoacetate → fumarate + acetoacetate (pqac-00000022, pqac-00000023) | Tyrosinemia type I (pqac-00000021, pqac-00000040) | No |


*Table: This table summarizes the five core enzymatic steps of tyrosine degradation, highlighting where HPD functions and where nitisinone exerts its therapeutic effect. It also links key enzyme deficiencies to their associated inherited metabolic disorders.*