Phenylalanine and tyrosine breakdown

Route: Phenylalanine → Tyrosine → 4-Hydroxyphenylpyruvate → Homogentisate → 4-Maleylacetoacetate → 4-Fumarylacetoacetate → Fumarate + Acetoacetate

Phenylalanine is first hydroxylated to tyrosine. Tyrosine aminotransferase then moves the amino group to alpha-ketoglutarate and gives 4-hydroxyphenylpyruvate. The next enzyme, 4-hydroxyphenylpyruvate dioxygenase, puts both atoms of O₂ into its product, homogentisate: one on the ring and one in the carboxyl group of the side chain. One CO₂ is released. Homogentisate dioxygenase cleaves the ring with another O₂ and gives 4-maleylacetoacetate. An isomerase that uses glutathione as a cofactor turns it into 4-fumarylacetoacetate, and a hydrolase splits that into fumarate and acetoacetate. Fumarate is an intermediate of the citric acid cycle, and acetoacetate is a ketone body. Alkaptonuria is caused by a lack of homogentisate dioxygenase: homogentisate builds up and is excreted in the urine, which turns dark on standing. Phenylketonuria is caused by a missing or weak phenylalanine hydroxylase or, more rarely, a lack of its tetrahydrobiopterin cofactor, so phenylalanine builds up in body fluids.

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Steps

Molecules

Build any of these from its atoms.

• Phenylalanine Build it
• Tyrosine Build it
• 4-Hydroxyphenylpyruvate Build it
• Homogentisate Build it
• 4-Maleylacetoacetate Build it
• 4-Fumarylacetoacetate Build it
• Fumarate Build it
• Acetoacetate Build it

Enzyme names and EC numbers are those used on the interactive board. Checked against sources: see the claim table in the repository (tools/pathway_data/checks).