2011
DOI: 10.1093/hmg/ddr165
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Abstract: The discovery of a pharmacological treatment for phenylketonuria (PKU) raised new questions about function and dysfunction of phenylalanine hydroxylase (PAH), the enzyme deficient in this disease. To investigate the interdependence of the genotype, the metabolic state (phenylalanine substrate) and treatment (BH(4) cofactor) in the context of enzyme function in vitro and in vivo, we (i) used a fluorescence-based method for fast enzyme kinetic analyses at an expanded range of phenylalanine and BH(4) concentratio… Show more

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Cited by 65 publications
(58 citation statements)
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“…A sapropterin loading test should be performed under standardized conditions and, if possible, in combination with genotyping, 41 but this requirement could change, depending on the patient's current blood Phe concentrations. 42 …”
Section: Discussionmentioning
confidence: 99%
“…A sapropterin loading test should be performed under standardized conditions and, if possible, in combination with genotyping, 41 but this requirement could change, depending on the patient's current blood Phe concentrations. 42 …”
Section: Discussionmentioning
confidence: 99%
“…PAH mutation analysis has utility in evaluating the clinical phenotype of PKU, for genetic consultation of patients' families, prenatal diagnosis, carrier detection, and also in refining diagnoses and anticipating dietary requirements (Guldberg et al, 1998;Güttler and Guldberg, 2000;Dobrowolski et al, 2007Dobrowolski et al, , 2009. Many BH4-responsive mutations have been identified in various studies, and it has been estimated that more than 30% of all HPA patients respond to BH4, thus revealing that identification of PAH mutations could be useful for BH4-based therapies (Zurflüh et al, 2008;Staudigl et al, 2011).…”
Section: Discussionmentioning
confidence: 99%
“…In contrast to the method published by Gersting et al [20], our method measures PAH activity at standardized Phe and BH 4 concentrations and may be a good screening method for selection of mutations of interest for the kinetic studies at different Phe and BH 4 concentrations [41]. Thus, the main application of this new method will be the quantification of the relative in vitro PAH activity in patients with PKU by expressing mutant proteins in COS-1 cells.…”
Section: Discussionmentioning
confidence: 97%