نتایج جستجو برای: phenylalanine hydroxylase pah deficiency

تعداد نتایج: 172799  

Journal: :The Journal of neuroscience : the official journal of the Society for Neuroscience 1999
L Zagreda J Goodman D P Druin D McDonald A Diamond

Phenylalanine hydroxylase (Pah)-deficient "PKU mice" have a mutation in the Pah gene that causes phenylketonuria (PKU) in humans. PKU produces cognitive deficits in humans if it is untreated. We report here the first evidence that the genetic mouse model of PKU (Pah(enu2)) also produces cognitive impairments. PKU mice were impaired on both odor discrimination reversal and latent learning compar...

2015
Yulan Qi Diane R. Mould Huiyu Zhou Markus Merilainen Donald G. Musson

BACKGROUND AND OBJECTIVES Untreated phenylketonuria (PKU), a hereditary metabolic disorder caused by a genetic mutation in phenylalanine hydroxylase (PAH), is characterized by elevated blood phenylalanine (Phe) and severe neurologic disease. Sapropterin dihydrochloride, a synthetic preparation of naturally occurring PAH cofactor tetrahydrobiopterin (BH4), activates residual PAH in a subset of p...

Journal: :Molecular genetics and metabolism 2005
Angel L Pey Aurora Martinez

The activity of phenylalanine hydroxylase (PAH) is regulated by the levels of both the substrate (L-Phe) and the natural cofactor (6R)-tetrahydrobiopterin (BH4). It has recently been observed that many PAH mutants associated with BH4-responsive phenylketonuria display abnormal kinetic and regulatory properties as shown by standard kinetic analyses. In this work, we have developed a high-sensiti...

2017
Sean M. Bell Dan J. Wendt Yanhong Zhang Timothy W. Taylor Shinong Long Laurie Tsuruda Bin Zhao Phillip Laipis Paul A. Fitzpatrick

Phenylketonuria (PKU) is a genetic metabolic disease in which the decrease or loss of phenylalanine hydroxylase (PAH) activity results in elevated, neurotoxic levels of phenylalanine (Phe). Due to many obstacles, PAH enzyme replacement therapy is not currently an option. Treatment of PKU with an alternative enzyme, phenylalanine ammonia lyase (PAL), was first proposed in the 1970s. However, iss...

2014
Silke Fuchs Volker Behrends Jacob G. Bundy Andrea Crisanti Tony Nolan

The blood meal of the female malaria mosquito is a pre-requisite to egg production and also represents the transmission route for the malaria parasite. The proper and rapid assimilation of proteins and nutrients in the blood meal creates a significant metabolic challenge for the mosquito. To better understand this process we generated a global profile of metabolite changes in response to blood ...

Journal: :The Journal of clinical investigation 2008
Angel L Pey Ming Ying Nunilo Cremades Adrian Velazquez-Campoy Tanja Scherer Beat Thöny Javier Sancho Aurora Martinez

Phenylketonuria (PKU) is an inborn error of metabolism caused by mutations in phenylalanine hydroxylase (PAH). Over 500 disease-causing mutations have been identified in humans, most of which result in PAH protein misfolding and increased turnover in vivo. The use of pharmacological chaperones to stabilize or promote correct folding of mutant proteins represents a promising new direction in the...

2017
Mike Petrassi Rob Barber Celine Be Sarah Beach Brian Cox Anne-Marie D’Souza Nick Duggan Martin Hussey Roy Fox Peter Hunt Gabor Jarai Takatoshi Kosaka Paul Oakley Viral Patel Neil Press David Rowlands Clemens Scheufler Oliver Schmidt Honnappa Srinivas Mary Turner Rob Turner John Westwick Alison Wolfreys Nuzhat Pathan Simon Watson Matthew Thomas

Pulmonary arterial hypertension (PAH) has demonstrated multi-serotonin receptor dependent pathologies, characterized by increased tone (5-HT1B receptor) and complex lesions (SERT, 5-HT1B, 5-HT2B receptors) of the pulmonary vasculature together with right ventricular hypertrophy, ischemia and fibrosis (5-HT2B receptor). Selective inhibitors of individual signaling elements - SERT, 5-HT2A, 5HT2B,...

2001
Jennifer Tipper Seymour Kaufman

Rats were given intraperitoneal injections of 2 mCi of carrier-free "Pi and substances known to activate liver phenylalanine hydroxylase. After 30 min, these animals were anesthetized and their livers removed for analysis of enzyme activity, 32Pi ncorporation into immunoprecipitated phenylalanine hydroxylase and [yS2P]ATP specific activity. Following glucagon treatment, rat liver phenylalanine ...

Journal: :Pediatrics 2003
Flemming Güttler Colleen Azen Per Guldberg Anne Romstad William B Hanley Harvey L Levy Reuben Matalon Bobbye M Rouse Friedrich Trefz Felix de la Cruz Richard Koch

OBJECTIVE The aim of the present study was to examine to what extent maternal and offspring phenylalanine hydroxylase (PAH) genotypes in conjunction with maternal IQ and dietary control during pregnancy are related to cognitive development in offspring of women with phenylketonuria (PKU). METHODS PAH gene mutations were determined in 196 maternal PKU subjects and their offspring. The women we...

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