Biogenic amines play an important role in brain metabolism and functioning, participation synaptic transmission as neurotransmitters neuromodulators (dopamine, serotonin, histamine others). Catecholamines are formed from the essential amino acid phenylalanine by hydroxylating it to tyrosine with enzyme phenylalanine-4-hydroxylase, which is subsequently converted dioxyphenylalanine (DOPA) tyrosi...

Tetrahydrobiopterin (BH(4)) is a required cofactor for the enzymatic activity of phenylalanine hydroxylase (PAH) and is synthesized de novo from GTP in several tissues. Heterologous expression of PAH in tissues other than liver is a potential novel therapy for human phenylketonuria that is completely dependent upon BH(4) supply in the PAH-expressing tissue. Previous experiments with liver PAH-d...

DHPR deficiency is a rare autosomal recessively inherited metabolic disorder of tetrahydrobiopterin (BH4) regeneration. Clinical symptoms may comprise microcephaly, developmental delay, ataxia and seizures. BH4 is the cofactor for the enzyme phenylalanine (Phe)hydroxylase (PAH), and for tryptophan and tyrosine hydroxylases, both of which are essential for serotonin and dopamine biosynthesis. We...

Background: Phenylketonuria as the most common genetic metabolic disorder is the result of disruption of the phenylalanine hydroxylase gene. This study was carried out to explore the phenylalanine hydroxylase gene mutation status of Iranian phenylketonuria patients.    Methods: Blood samples were collected from 30 patients, and hot spot areas of the phenylalanine hydroxylase gene, in...

Phenylketonuria (PKU) is a metabolic disorder, in which loss of phenylalanine hydroxylase activity results in neurotoxic levels of phenylalanine. We used the Pah(enu2/enu2) PKU mouse model in short- and long-term studies of enzyme substitution therapy with PEGylated phenylalanine ammonia lyase (PEG-PAL conjugates) from 4 different species. The most therapeutically effective PAL (Av, Anabaena va...

BACKGROUND Hyperphenylalaninemia is a common inherited metabolic disease that is due to phenylalanine hydroxylase deficiency, and at least half the affected patients have mild clinical phenotypes. Treatment with a low-phenylalanine diet represents a substantial psychosocial burden, but alternative treatments have not been effective. METHODS To explore the therapeutic efficacy of tetrahydrobio...

We report prenatal diagnosis of phenylketonuria by linkage analysis of the markers linked to the phenylalanine hydroxylase (PAH) gene. Three markers comprising STR (TCTAT)n in intron 3, VNTR (30bp long cassette) in the 3' UTR and Xmn1 RFLP were ascertained in the affected child, the parents and the chorionic villi sample. The foetus was confirmed to be heterozygous for the mutant allele. The di...

The newborn screening for phenylketonuria (PKU) has become a common practice in many countries. The success of this type of mass screening is the result of the reliability of the Guthrie test in the identification of high blood phenylalanine levels. Recently, new syndromes other than PKU have been recognized that give high blood phenylalanine levels. These syndromes are referred to as “atypical...

M I C E homozygous for the dilute-lethal (8) gene have been reported by COLEMAN (1960) and RAUCH and YOST (1963) to have low liver phenylalanine hydroxylase activity. This deficiency in phenylalanine metabolism has been reported to be due to the presence of an inhibitor of the hydroxylase localized in a particulate fraction of liver (15,000 x g sediment). These investigators have pointed out th...