97 research outputs found
7-Substituted pterins in humans with suspected pterin-4a-carbinolamine dehydratase deficiency : mechanism of formation via non-enzymatic transformation from 6-substituted pterins
A recently described new form of hyperphenylalaninemia is characterized by the excretion of 7-substituted isomers of biopterin and neopterin and 7-oxo-biopterin in the urine of patients. It has been shown that the 7-substituted isomers of biopterin and neopterin derive from L-tetrahydrobiopterin and D-tetrahydroneopterin and are formed during hydroxylation of phenylalanine to tyrosine with rat liver dehydratase-free phenylalanine hydroxylase.We have now obtained identical results using human phenylalanine hydroxylase. The identity of the pterin formed in vitro and derived from L-tetrahydrobiopterin as 7-(1',2'-dihydroxypropyl)pterin was proven by gas-chromatography mass spectrometry. Tetrahydroneopterin and 6-hydroxymethyltetrahydropterin also are converted to their corresponding 7-substituted isomers and serve as cofactors in the phenylalanine hydroxylase reaction. Dihydroneopterin is converted by dihydrofolate reductase to the tetrahydro form which is biologically active as a cofactor for the aromatic amino acid monooxygenases. The 6-substituted pterin to 7-substituted pterin conversion occurs in the absence of pterin-4a-carbinolamine dehydratase and is shown to be a nonenzymatic process. 7-Tetrahydrobiopterin is both a substrate (cofactor) and a competitive inhibitor with 6-tetrahydrobiopterin (Ki ≈ 8 μM) in the phenylalanine hydroxylase reaction. For the first time, the formation of 7-substituted pterins from their 6-substituted isomers has been demonstrated with tyrosine hydroxylase, another important mammalian enzyme which functions in the hydroxylation of phenylalanine and tyrosine
Quantitative functional magnetic resonance imaging of brain activity using bolus-tracking arterial spin labeling
Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) is the most widely used method for mapping neural activity in the brain. The interpretation of altered BOLD signals is problematic when cerebral blood flow (CBF) or cerebral blood volume change because of aging and/or neurodegenerative diseases. In this study, a recently developed quantitative arterial spin labeling (ASL) approach, bolus-tracking ASL (btASL), was applied to an fMRI experiment in the rat brain. The mean transit time (MTT), capillary transit time (CTT), relative cerebral blood volume of labeled water (rCBVlw), relative cerebral blood flow (rCBF), and perfusion coefficient in the forelimb region of the somatosensory cortex were quantified during neuronal activation and in the resting state. The average MTT and CTT were 1.939±0.175 and 1.606±0.106 secs, respectively, in the resting state. Both times decreased significantly to 1.616±0.207 and 1.305±0.201 secs, respectively, during activation. The rCBVlw, rCBF, and perfusion coefficient increased on average by a factor of 1.123±0.006, 1.353±0.078, and 1.479±0.148, respectively, during activation. In contrast to BOLD techniques, btASL yields physiologically relevant indices of the functional hyperemia that accompanies neuronal activation
Phenylalanine hydroxylase-stimulating protein/pterin-4alpha-carbinolamine dehydratase from rat and human liver : purification, characterization, and complete amino acid sequence
Phenylalanine hydroxylase-stimulating protein, also known as pterin-4α-carbinolamine dehydratase (PHS/PCD), was purified from rat and, for the first time, from human liver. We obtained their complete protein primary sequence using a combination of liquid secondary ionization mass spectrometry/tandem quadrupole mass spectrometry, electrospray ionization mass spectrometry, and Edman microsequence analysis. The amino acid sequences of human and rat PHS/PCD were found to be identical. Surprisingly, the primary structure of PHS/PCD is also essentially identical to a protein of the cell nucleus, named dimerization cofactor of hepatocyte nuclear factor 1α, recently reported to be involved in transcription (Mendel, D. M., Khavari, P. A., Conley, P. B., Graves, M. K., Hansen, L. P., Admon, A., and Crabtree, G. R. (1991) Science 254, 1762-1767)
The Service–Profit Chain: a Meta-Analytic Test of a Comprehensive Theoretical Framework
The service–profit chain has served as a prominent guidepost for service managers and researchers alike. This meta-analysis provides the first comprehensive test of it, showing that all the links proposed in the service–profit chain (SPC) appear statistically significant and substantial. However, the effect sizes vary considerably, partly according to the type of service provided. Meta-analytic structural equation models show that internal service quality translates into service performance through various mechanisms, beyond employee satisfaction, and highlight the importance of the service encounter and customer relationship characteristics for customer responses. The findings indicate the need to integrate complementary paths in the SPC framework and also challenge the implicit SPC rationale that firms should always maximize employee satisfaction and external service quality to optimize firm performance
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