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Epidemiological evidence suggests that isoflavone phytoestrogens may reduce the risk of cancer, osteoporosis, and heart disease, effects at least partially mediated by estrogen receptors alpha and beta (ERalpha and ERbeta). Because isoflavone dietary supplements are becoming increasingly popular and are frequently advertised as natural alternatives to(More)
Dopa decarboxylase (DDC), or aromatic amino acid decarboxylase (AADC), is a pyridoxal 5'-phosphate enzyme responsible for the production of the neurotransmitters dopamine and serotonin. Deficit of this enzyme causes AADC deficiency, an inherited neurometabolic disorder. To date, 18 missense homozygous mutations have been identified through genetic screening(More)
Dopa or aromatic amino acid decarboxylase (DDC, AADC) is a pyridoxal 5'-phosphate-dependent enzyme that catalyses the production of the neurotransmitters dopamine and serotonin. Among the so far identified mutations associated with AADC deficiency, an inherited rare neurometabolic disease, the S250F mutation is the most frequent one. Here, for the first(More)
Human Dopa decarboxylase (hDDC), a pyridoxal 5'-phosphate (PLP) enzyme, displays maxima at 420 and 335 nm and emits fluorescence at 384 and 504 nm upon excitation at 335 nm and at 504 nm when excited at 420 nm. Absorbance and fluorescence titrations of hDDC-bound coenzyme identify a single pK(spec) of ~7.2. This pK(spec) could not represent the ionization(More)
Liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate (PLP) enzyme, exists as two polymorphic forms, the major (AGT-Ma) and the minor (AGT-Mi) haplotype. Deficit of AGT causes Primary Hyperoxaluria Type 1 (PH1), an autosomal recessive rare disease. Although ~one-third of the 79 disease-causing missense mutations segregates on(More)
The functional deficit of alanine:glyoxylate aminotransferase (AGT) in human hepatocytes leads to a rare recessive disorder named primary hyperoxaluria type I (PH1). PH1 is characterized by the progressive accumulation and deposition of calcium oxalate stones in the kidneys and urinary tract, leading to a life-threatening and potentially fatal condition. In(More)
In this work the dimerization process of the minor allelic form of human alanine glyoxylate aminotransferase, a pyridoxal 5'-phosphate enzyme, was investigated. Bioinformatic analyses followed by site-directed mutagenesis, size exclusion chromatography and catalytic activity experiments allowed us to identify Arg118, Phe238 and Phe240 as interfacial(More)
We report here a clinical case of a patient with a novel mutation (Arg347→Gly) in the gene encoding aromatic amino acid decarboxylase (AADC) that is associated with AADC deficiency. The variant R347G in the purified recombinant form exhibits, similarly to the pathogenic mutation R347Q previously studied, a 475-fold drop of kcat compared to the wild-type(More)
The rare disease Primary Hyperoxaluria Type I (PH1) results from the deficit of liver peroxisomal alanine:glyoxylate aminotransferase (AGT), as a consequence of inherited mutations on the AGXT gene frequently leading to protein misfolding. Pharmacological chaperone (PC) therapy is a newly developed approach for misfolding diseases based on the use of small(More)
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