[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Phenylalanine and tyrosine metabolism [Biochemistry](https://durgical.com/en/biochemistry/) · Metabolic pathway # Phenylalanine and tyrosine metabolism Phenylalanine becomes tyrosine, which is then broken down to fumarate and acetoacetate. Each blocked enzyme gives a classic disease. Updated 2026-11-01 ## Interactive map ## Key facts - Phenylalanine hydroxylase (liver) needs tetrahydrobiopterin (BH4), O₂ and Fe²⁺; its failure causes phenylketonuria. - Phenylalanine is essential; tyrosine becomes essential when the hydroxylase does not work. - Both are glucogenic and ketogenic at once: they give fumarate (glucose) and acetoacetate (ketone bodies). - Blocks in order: PAH → phenylketonuria; TAT → tyrosinaemia II; HGD → alkaptonuria; FAH → tyrosinaemia I. - Tyrosine also gives catecholamines, melanin and thyroid hormones. ## Regulation - Phenylalanine activates its own hydroxylase by binding the regulatory domain; phosphorylation by PKA (glucagon) also activates it. - Glucocorticoids induce tyrosine aminotransferase in the liver. ## The steps, one by one - **Step 1 · [Phenylalanine hydroxylase (PAH)](https://durgical.com/en/biochemistry/enzymes/phenylalanine-hydroxylase/)** irreversible [Phenylalanine](https://durgical.com/en/biochemistry/molecules/phenylalanine/) + [Tetrahydrobiopterin](https://durgical.com/en/biochemistry/molecules/tetrahydrobiopterin/) + o2 → [Tyrosine](https://durgical.com/en/biochemistry/molecules/tyrosine/) + Dihydrobiopterin (BH₂) + H₂O Adds an OH to the ring of phenylalanine to make tyrosine; BH4 gives the electrons and is left as BH₂. **If it fails:** Phenylketonuria: phenylalanine builds up and harms the brain; BH4 deficiency gives a similar picture. [Phenylketonuria (PKU) →](https://durgical.com/en/conditions/phenylketonuria/) - **Step 2 · Tyrosine aminotransferase (TAT)** [Tyrosine](https://durgical.com/en/biochemistry/molecules/tyrosine/) + α-ketoglutarate ⇌ p-Hydroxyphenylpyruvate + [Glutamate](https://durgical.com/en/biochemistry/molecules/glutamate/) Moves the amino group of tyrosine to α-ketoglutarate, leaving the keto acid p-hydroxyphenylpyruvate. **If it fails:** Tyrosinaemia II (oculocutaneous): corneal ulcers, palm and sole lesions and sometimes intellectual disability. - **Step 3 · 4-Hydroxyphenylpyruvate dioxygenase (HPPD)** irreversible p-Hydroxyphenylpyruvate + o2 → Homogentisate + CO₂ With oxygen it decarboxylates the keto acid and shifts the side chain on the ring, making homogentisate. **If it fails:** Its failure causes rare tyrosinaemia III; nitisinone blocks it on purpose in tyrosinaemia I. [Tyrosinaemia type I (hepatorenal) →](https://durgical.com/en/conditions/tyrosinaemia-type-i/) - **Step 4 · Homogentisate 1,2-dioxygenase (homogentisate oxidase, HGD)** irreversible Homogentisate + o2 → Maleylacetoacetate Opens the aromatic ring of homogentisate with oxygen to make maleylacetoacetate. **If it fails:** Alkaptonuria: homogentisate builds up, darkens urine and stains cartilage and valves. [Alkaptonuria →](https://durgical.com/en/conditions/alkaptonuria/) - **Step 5 · Maleylacetoacetate isomerase (GSTZ1)** Maleylacetoacetate ⇌ Fumarylacetoacetate Flips a double bond from cis to trans (maleyl → fumaryl) using glutathione. **If it fails:** Its deficiency is very rare and nearly silent, because a non-enzymatic bypass exists. - **Step 6 · Fumarylacetoacetate hydrolase (FAH)** irreversible Fumarylacetoacetate + H₂O → fumarate + [Acetoacetate](https://durgical.com/en/biochemistry/molecules/acetoacetate/) Splits fumarylacetoacetate into fumarate (to the Krebs cycle and glucose) and acetoacetate (a ketone body). **If it fails:** Tyrosinaemia I: fumarylacetoacetate and succinylacetone build up and damage liver, kidney and nerves. [Tyrosinaemia type I (hepatorenal) →](https://durgical.com/en/conditions/tyrosinaemia-type-i/) ## Clinical notes - Newborn screening detects phenylketonuria; in Colombia, Law 1980 of 2019 created the newborn screening programme. - Nitisinone blocks 4-hydroxyphenylpyruvate dioxygenase and prevents succinylacetone, the toxin of tyrosinaemia I, from forming. - In alkaptonuria, homogentisic acid darkens urine on standing in air and deposits in cartilage (ochronosis). - Oculocutaneous albinism hits a side branch: melanocyte tyrosinase, which makes melanin. ## Pathways - [Phenylalanine and tyrosine metabolism](https://durgical.com/en/biochemistry/pathways/phenylalanine-and-tyrosine-metabolism/) ## Related conditions - [Phenylketonuria (PKU)](https://durgical.com/en/conditions/phenylketonuria/) - [Tyrosinaemia type I (hepatorenal)](https://durgical.com/en/conditions/tyrosinaemia-type-i/) - [Alkaptonuria](https://durgical.com/en/conditions/alkaptonuria/) - [Oculocutaneous albinism](https://durgical.com/en/conditions/oculocutaneous-albinism/) ## Related - [Phenylalanine](https://durgical.com/en/biochemistry/molecules/phenylalanine/) - [Tyrosine](https://durgical.com/en/biochemistry/molecules/tyrosine/) - [Tetrahydrobiopterin (BH4)](https://durgical.com/en/biochemistry/molecules/tetrahydrobiopterin/) - [Phenylalanine hydroxylase (PAH)](https://durgical.com/en/biochemistry/enzymes/phenylalanine-hydroxylase/) - [Tyrosine hydroxylase](https://durgical.com/en/biochemistry/enzymes/tyrosine-hydroxylase/) - [Glutamate (glutamic acid)](https://durgical.com/en/biochemistry/molecules/glutamate/) - [Glucogenic and ketogenic amino acids](https://durgical.com/en/biochemistry/topics/glucogenic-and-ketogenic-amino-acids/) - [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/) ## Test yourself Think of the answer, then tap the question to see it. ## Which cofactors does phenylalanine hydroxylase need? Tetrahydrobiopterin (BH4), oxygen and ferrous iron; that is why BH4 deficiency also raises phenylalanine. ## Which enzyme is missing in alkaptonuria? Homogentisate 1,2-dioxygenase: homogentisic acid builds up, darkens urine and stains cartilage. ## Why does nitisinone help tyrosinaemia I if it blocks the same pathway? It blocks an earlier step (HPPD), so fumarylacetoacetate and succinylacetone, the toxins, are not made; tyrosine stays high, which is less harmful. ## Which products does tyrosine breakdown end in? Fumarate, which is glucogenic, and acetoacetate, which is ketogenic. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/pathways/phenylalanine-and-tyrosine-metabolism/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Phenylalanine and tyrosine metabolism](https://reactome.org/PathwayBrowser/#/R-HSA-8963691) (Reactome, 2026); [Tyrosine catabolism](https://reactome.org/PathwayBrowser/#/R-HSA-8963684) (Reactome, 2026); [Tyrosinemia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/tyrosinemia/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011). [← All of biochemistry](https://durgical.com/en/biochemistry/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/biochemistry/pathways/phenylalanine-and-tyrosine-metabolism/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/pathways/phenylalanine-and-tyrosine-metabolism/