PKU is a congenital amino acid metabolic disorder. In one of the following rare variants of PKU Dihydro Biopterin synthesis is affected. The enzyme deficient is:
Ans:C.)Dihydropterin reductase.METABOLISM OF PHENYLALANINEOverview of pathway:Phenylalanine can be conveed into one of two products.If the a-amino group is removed from phenylalanine, it is transformed into phenylpyruvate, which is eventually broken down into fumarate and entered into the citric acid cycle.Alternatively, phenylalanine can be used to synthesize tyrosine. The conversion of phenylalanine to tyrosine is catalyzed by phenylalanine hydroxylase .* Impoant enzymes:Phenylalanine hydroxylase: Hydroxylates phenylalanine to tyrosine. Requires tetrahydrobiopterin and O 2 as cofactors.Dihydrobiopterin reductase: Regenerates tetrahydrobiopterin by reducing dihydrobiopterin to form tetra- hydrobiopterin. Requires a molecule of NADPH.* Diseases: When phenylalanine hydroxylase or dihydropteridine reductase is deficient, phenylketonuria results.Pathophysiology :When this enzyme is deficient, phenylalanine builds up. High levels of phenylalanine lead to severe brain damage by competitively inhibiting amino acid transpo required for protein synthesis, impairing polyribosome stabilization, reducing myelin production, and decreasing the formation of norepinephrine and serotonin.Phenylalanine is also a competitive inhibitor of tyrosinase, a key enzyme in the pathway of melanin synthesis, and thereby leads to hypopigmentation of the hair and skin.Clinical ManifestationsMental and growth retardation ; microcephaly; decreased pigmentation (blonde and blue-eyed) ; eczema; "mousy" body odor; heavy perspiration; musty urine odor; hypeonia, hyperreflexia.Lab findings: Phenylketones detected in urine (phenylacetate, phenyllactate, and phenyl-pyruvate); positive Guthrie test (measures phenylalanine in blood) at bih.Treatment :Decreased intake of phenylalanine (avoid aspaame, which is found in Nutrasweet) and increased dietary tyrosine (essential amino acids for patients with this disorder).
Histidine decarboxylase
Phenylalanine hydroxylase
Dihydropterin reductase
Tyrosine deficiency