Phenylalanine and tyrosine metabolism

  • Phe & Tyr pathway

  • Phenylalanine (Phe) and tyrosine (TYR) metabo­lism takes place in the cytoplasm. 

    Breakdown:

    • PAH: Phe hydroxylase, requires cofactor tetrahydrobiopterin (BH4); deficiency causes the accumulation of Phe which is transaminated to phenylpyruvate and other phenylketones. 
    • TAT: TYR aminotransferase = reversible transamination
    • HPD: 4-OH-phenylpyruvate dioxygenase; subfunction deficiency by a specific mutation can generate the complex amino acid hawkinsin. 
    • HGD: homogentisate dioxygenase = cleavage of the phenolic ring is achieved by  (HGD). 
    • GSTZ1: glutathione S-transferase zeta-1 = isomerization of maleylacetoacetate to fumarylacetoacetate, may also happen non-enzymatically.
    • FAH: fumaryl­acetoacetate hydrolase; deficiency causes accumu­lation of maleylacetoacetate, fumarylaceto­acetate, and succinyl­acetoacetate and ‑acetone. These highly toxic substances inhibit or interfere with several enzymes such as HPD (­↑TYR), methionine adenosyltransferase (­↑Met), and aminolaevulinate dehydratase (→porphyrias), and are carcinogenic (alkylation of DNA).

    Biosynthetic enzymes (not shown) using TYR as precursor:

    • TYR: tyrosinase = first step in melanin biosynthesis 
    • TYH: TYR hydroxylase = first step in catecholamine biosynthesis