Abstract Phenylketonuria (PKU) is caused by autosomal recessive variants in phenylalanine hydroxylase ( PAH ), leading to systemic accumulation of L-phenylalanine (L-Phe) that may reach neurotoxic levels. A homozygous Pah - R261Q mouse, with a highly prevalent misfolding variant humans, reveals the expected hepatic activity decrease, L-Phe increase, L-tyrosine and L-tryptophan tetrahydrobiopter...

Site-directed mutagenesis was used to investigate whether phenylalanine residues in predicted transmembrane sequences play essential roles in the function of human P-glycoprotein. Mutant cDNAs, in which codons for each of the 31 phenylalanine residues were changed to alanine, were expressed in mouse NIH 3T3 cells and analyzed with respect to their ability to confer resistance to various drugs. ...

Accumulating evidence suggests that hyperphenylalaninemia in phenylketonuria (PKU) can cause neuropsychological and psychosocial problems in diet-off adult patients, and that such symptoms improve after resumption of phenylalanine-restricted diet, indicating the need for lifetime low-phenylalanine diet. While limiting protein intake, dietary therapy should provide adequate daily intake of energ...

In order to investigate the source of free amino acids found in the gut lumen during absorption of dipeptides, as well as evaluating the role of brush border peptidases in the mucosal hydrolysis of dipeptides during absorption, rates of dipeptide disappearance and appearance of hydrolytic products were measured during perfusion of rat jejunum and ileum in vivo with buffered and unbuffered 10 mM...

The phenylalanine biosynthetic pathway in the yeast Rhodotorula glutinis was examined, and the following results were obtained. (i) 3-Deoxy-D-arabinoheptulosonate-7-phosphate (DAHP) synthase in crude extracts was partially inhibited by tyrosine, tryptophan, or phenylalanine. In the presence of all three aromatic amino acids an additive pattern of enzyme inhibition was observed, suggesting the e...

BACKGROUND It has been previously postulated that high phenylalanine (Phe) might disturb intracerebral dopamine production, which is the main regulator of prolactin secretion in the pituitary gland. Previously, various associations between Phe and hyperprolactinemia were revealed in studies performed in phenylketonuria (PKU) children and adolescents. The aim of the present study was to clarify ...

Early diagnosis of dopa-responsive dystonia (DRD) and its delineation from other dystonic syndromes is of great relevance because DRD is an eminently treatable condition. The possible relevance of the phenylalanine loading test (Phe-L) in differentiating DRD from primary focal and generalized dystonia was investigated. A marked difference in the phenylalanine/tyrosine ratio between patients wit...

Phenylalanine loading has been proposed as a diagnostic test for autosomal dominant DRD (dopa-responsive dystonia), and recently, a phenylalanine/tyrosine (phe/tyr) ratio of 7.5 after 4 h was reported as diagnostic of DRD. To test the utility of this test in another sample with DRD, we administered an oral challenge of phenylalanine (100 mg/kg) to 11 individuals with DRD and one non-manifesting...

OBJECTIVE To identify patients responsive to tetrahydrobiopterin (BH4) in a sample of Brazilians with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency (HPA-PAH). METHODS Interventional study, convenience sampling. The inclusion criteria were: diagnosis of HPA-PAH; age ≥ 7 years; phenylalanine-restricted diet and phenylalanine (Phe) levels ≥ 6 mg/dL in all blood tests 1 year b...

The non-enzymatic synthesis of N-benzyloxycarbonyl-L-phenylalanyl-L-leucine (Cbz-Phe-Leu) from lipophilic N-benzyloxycarbonyl-L-phenylalanine (Cbz-Phe) and hydrophilic L-leucine (Leu), by N, N’-dicyclohexylcarbodiimide (DCC) as a condensing agent, was carried out using reversed micellar system composed bis(2-ethylhexyl) sodium sulfosuccinate (AOT) surfactant isooctane. We successfully synthesiz...