6 Phenylalanine and tyrosine

• Phenylalanine and tyrosine are structurally related aromatic amino acids
• Phenylalanine


  Essential amino acid
• Tyrosine


  Non-essential amino acid
• Ingestion of tyrosine can reduce the dietary requirement of phenylalanine
• Sparing action


  Tyrosine on phenylalanine
• The predominant metabolism of phenylalanine occurs through tyrosine
• Tyrosine is incorporated into proteins and is involved in the synthesis of a variety of biologically important compounds
• Biologically important compounds synthesized from tyrosine

  • Epinephrine
  • Norepinephrine
  • Dopamine
  • Thyroid hormones
  • Melanin
• During degradation, phenylalanine and tyrosine are converted to metabolites which can serve as precursors for the synthesis of glucose and fat
• Phenylalanine and tyrosine are both

  • Glucogenic
  • Ketogenic
• Biochemists attach special significance to phenylalanine and tyrosine metabolism for two reasons
• Conversion of phenylalanine to tyrosine occurs under normal circumstances
• Degradation of phenylalanine


  Phenylalanine is hydroxylated at para-position by phenylalanine hydroxylase to produce tyrosine
• The enzyme phenylalanine hydroxylase is present in the liver
• 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
• Due to a defect in phenylalanine hydroxylase, the conversion of phenylalanine to tyrosine is blocked resulting in the disorder phenylketonuria (PKU)
• Amino acids can serve as precursors for the synthesis of glucose and fat
• Glucogenic


  Amino acids that can be converted into glucose
• Ketogenic


  Amino acids that can be converted into ketone bodies
• Phenylalanine and tyrosine metabolism is significant for synthesis of biologically important compounds and metabolic disorders due to enzyme defects
• Conversion of phenylalanine to tyrosine

  1. Hydroxylation by phenylalanine hydroxylase

  2. Produces tyrosine

  3. Incorporates molecular oxygen

  4. Forms water
• Phenylalanine hydroxylase


  An enzyme present in the liver that converts phenylalanine to tyrosine
• Due to a defect in phenylalanine hydroxylase, the conversion of phenylalanine to tyrosine is blocked resulting in phenylketonuria (PKU)
• Degradation of tyrosine (phenylalanine)

  1. Conversion of phenylalanine to tyrosine

  2. Transamination to p-hydroxyphenylpyruvate

  3. Hydroxylation to produce homogentisate

  4. Cleavage of benzene ring to form 4-maleylacetoacetate

  5. Isomerization to form 4-fumaryl acetoacetate

  6. Hydrolysis to liberate fumarate and acetoacetate
• Homogentisate oxidase


  An iron metalloprotein that cleaves the benzene ring of homogentisate
• Fumarate


  An intermediate of the citric acid cycle
• Acetoacetate


  A ketone body from which fat can be synthesized
• Phenylalanine and tyrosine are both glucogenic and ketogenic
• Inborn errors of metabolism comprise a large class of genetic diseases involving disorders of metabolism
• Inherited metabolic diseases are categorized as disorders of carbohydrate metabolism, amino acid metabolism, organic acid metabolism, or lysosomal storage diseases