Phenylalanine hydroxylase (PAH) deficiency, commonly known as phenylketonuria (PKU), is one of the most common inborn errors of amino acid metabolism. It is inherited as an autosomal recessive trait. Prevalance of PKU is approximately 1:10000 in Europe and 1:15000 in the USA but may vary widely in other regions of the world [1]. Due to the high rate of consanguineous marriages (20-25%) [2], dis...

Phosphorylation of phenylalanine hydroxylase (PAH) at Ser by cyclic AMP-dependent protein kinase is a post-translational modification that increases its basal activity and facilitates its activation by the substrate L-Phe. So far there is no structural information on the flexible N-terminal tail (residues 1–18), including the phosphorylation site. To get further insight into the molecular basis...

DCoH, the dimerization cofactor of the HNF-1 homeodomain proteins (hepatocyte nuclear factor-1alpha and beta), is involved in gene expression by associating with these transcription factors. The protein also called PCD for pterin-4alpha-carbinolamine dehydratase is a bifunctional factor as it catalyzes also the regeneration of tetrahydrobiopterin. This coenzyme is used by the enzyme phenylalani...

Ole Andreas Andersen received hisM.Sc and Ph.D from theUniversity of Tromsø, Norway, in 1998 and 2003, respectively. His Ph.Dwork was supervised by Prof. Edward Hough and comprised crystallographic and biochemical studies on human phenylalanine hydroxylase. Andersen had a postdoctoral fellowship for one year at The Norwegian Structural Biology Centre in Tromsø under the supervision of Prof. Arn...

Phenylketonuria patients harboring a subset of phenylalanine hydroxylase (PAH) mutations have recently shown normalization of blood phenylalanine levels upon oral administration of the PAH cofactor tetrahydrobiopterin [(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4)]. Several hypotheses have been put forward to explain BH4 responsiveness, but the molecular basis for the corrective effect(s) of...

BACKGROUND The variable numbers of tandem-repeat (VNTR) alleles at the phenylalanine hydroxylase (PAH) gene have been used in carrier detection and prenatal diagnosis in phenylketonuria families. This study was carried out to analyze VNTR alleles at the PAH gene in Iranian Azeri Turkish population. METHODS In this study, 200 alleles from general population were studied by PCR. RESULTS The f...

Continued high levels of phenylalanine hydroxylase in cultured H4-II-E-C3 rat hepatoma cells require either serum or glucocorticoids in the culture medium. Upon withdrawal of serum, cellular phenylalanine hydroxylase levels decay exponentially with a half-life of 22 hours for about 60 hours, after which time a low, constant enzyme content persists for at least 96 hours. This decline of phenylal...

Maximum inhibition of phenylalanine hydroxylase activity in the liver (85%) and in the kidney (50%) of suckling rats required the administration of over 9 mumol of p-chlorophenylalanine/10g body weight. Despite the decrease in the total activity from 184 to 34 units per 10g body weight, the injection of as much as 26 mumol of phenylalanine was required for its concentration in plasma to be stil...