Metabolism of Phenylalanine & Tyrosine

Metabolism of Phenylalanine & Tyrosine

Metabolism of Phenylalanine & Tyrosine


       At the end of this lecture, students will be able to

      Explain the metabolism of phenylalanine & tyrosine and their metabolic disorders

Metabolism of phenylalanine & tyrosine

       Phenylalanine and tyrosine are structurally related aromatic amino acids

       Phenylalanine is an essential amino acid while tyrosine is non-essential

       Besides its incorporation into proteins, the only function of phenyl alanine is its conversion to tyrosine

       For this reason, ingestion of tyrosine can reduce the dietary requirement of phenylalanine

       This phenomenon is referred to as ‘sparing action’ of  tyrosine on phenylalanine

Biosynthesis (conversion of Phenylalanine and Tyrosine)

       Degradation of phenylalanine mostly occurs through tyrosine

       Phenylalanine is hydroxylated at para-position by phenylalanine hydroxylase to produce tyrosine(p-hydroxyphenylalanine)

       This is an irreversible reaction and require phenylalanine hydroxylase and specific coenzyme biopterin, which is structurally related to folate

       The active form of biopterin is tetrahydrobiopterin

       In the phenylalanine hydroxylase reaction, tetrahydrobiopterin is oxidized to dihydrobiopterin

       Tetrahydrobiopterin is regenerated by NADPH-dependent dihydrobiopterin reductase

       The enzyme phenylalanine hydroxylase (liver) convert phenylalanine to tyrosine, the reaction involves the incorporation of one atom of molecular oxygen (O2) into the para position of phenylalanine while the other atom of O2 is reduced to form water

       Tetrahydrobiopterin that supplies the reducing equivalents which, in turn, are provided by NADPH

       Defect in phenylalanine hydroxylase leads to phenylketonuria (PKU)


       Phenylketonuria: Defective phenylalanine hydroxylase

       Tyrosinemia type II: Defective Tyrosine transaminase

       Neonatal tyrosinemia: Defective p-hydroxyphenyl pyruvate dioxygenase (Tyrosinemia type III)

       Alkaptonuria: defective homogentisate oxidase

       Tyrosinemia type I: Defective fumarylacetoacetate hydroxylase and/or maleyl acetoacetate isomerase

       Albinism: Defective tyrosinase

Metabolic disorders

Phenylketonuria (PKU)

       Deficiency of phenylalanine hydroxylase – classical

       New variant – due to deficiency of dihydrobiopterin reductase

       Mental retardation

       Effect on pigmentation

       Treatment- Dietary approach

Tyrosinemia type II:

       Very rare

       Herpetiformic keratitis

       Palmoplanter hyperkeratosis with ulcers

       PMR, growth retardation

       Dietary treatment

       Richner-Hanhart syndrome

       Defective enzyme: tyrosine transaminase

       Accumulation of tyrosine and its metabolites

       Skin (dermatitis) and eye lesions

       Mental retardation

Neonatal Tyrosinemia

       Absence of p-hydroxyl phenyl pyruvate dioxygenase

       Well responded to ascorbic acid therapy

Tyrosinemia type 1

       Deficiency of fumarylacetoacetyl hydroxylase and/or maleylacetoacetyl isomerase


       Liver failure

       Poly neuropathy


       Renal tubular dysfunction


       Deficiency of Homogentisate oxidase


       Lack of synthesis of pigment melanin

       Defect in tyrosinase-enzyme responsible for synthesis of melanin

       Deficiency or lack of the enzyme tyrosinase.

       Decrease in melanosomes of melanocytes.

       Impairment in melanin polymerization.

       Lack of protein matrix in melanosomes.

       Limitation of substrate (tyrosine) availability.

       Presence of inhibitors of tyrosinase.

Diagnosis and Treatment

Early diagnosis of phenylalanine and tyrosine metabolic disorders is crucial for effective management.

Screening methods such as newborn screening allow for the early detection of these disorders, enabling timely intervention through dietary modifications and supplementation with cofactors like BH4.


       Children with Alkaptonuria are asymptomatic, besides producing brown or black urine

       Treatment for classic PKU is a strict PHE-restricted diet supplemented by a medical formula containing amino acids and other nutrients

Unique FAQs:

  1. What are the symptoms of phenylketonuria (PKU)?
    • Symptoms of PKU include intellectual disability, seizures, behavioral problems, and a musty odor in the breath and urine.
  2. Can phenylketonuria (PKU) be cured?
    • There is no cure for PKU, but early diagnosis and dietary management can prevent symptoms and complications.
  3. What foods should individuals with PKU avoid?
    • Individuals with PKU should avoid high-protein foods containing phenylalanine, such as meat, fish, eggs, dairy, and certain grains.
  4. Is tyrosinemia a treatable condition?
    • Tyrosinemia can be managed through dietary restrictions and medication, but severe cases may require liver transplantation.
  5. Are there any alternative treatments for phenylketonuria (PKU)?
    • Emerging therapies such as enzyme replacement and gene therapy are being investigated as potential alternative treatments for PKU.

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