Tyrosine hydroxylase. the initial step in norepinephrine biosynthesis.
TL;DR: It has now been possible to demonstrate that brain, adrenal medulla, and sympathetically innervated tissues contain a specific hydroxylase that catalyzes the conversion of L-tyrosine to dopa.
About: This article is published in Journal of Biological Chemistry.The article was published on 1964-09-01 and is currently open access. It has received 2037 citations till now. The article focuses on the topics: Tyrosine hydroxylase & Tyrosine.
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TL;DR: The determination of the electrophysiological characteristics of a population of cells directly identified as containing a specific neurotransmitter may allow one to construct better models of a system's functioning and may be important functionally with respect to a possible modulatory effect of dopamine in postsynaptic target areas.
919 citations
840 citations
TL;DR: The identification of four independent mutations of the gene for GTP cyclohydrolase I in patients with HPD, as well as a marked decrease in the enzymes activity in mononuclear blood cells, confirms that the GTP cycling enzyme gene is a causative gene for HPD/DRD.
Abstract: Hereditary progressive dystonia with marked diurnal fluctuation (HPD) (also known as dopa responsive dystonia) is a dystonia with onset in childhood that shows a marked response without any side effects to levodopa. Recently the gene for dopa responsive dystonia (DRD) was mapped to chromosome 14q. Here we report that GTP cyclohydrolase I is mapped to 14q22.1-q22.2. The identification of four independent mutations of the gene for GTP cyclohydrolase I in patients with HPD, as well as a marked decrease in the enzyme's activity in mononuclear blood cells, confirms that the GTP cyclohydrolase I gene is a causative gene for HPD/DRD. This is the first report of a causative gene for the inherited dystonias.
729 citations
TL;DR: Data suggest that α-synuclein plays a role in the regulation of dopamine biosynthesis, acting to reduce the activity of tyrosine hydroxylase.
Abstract: The α-synuclein gene is implicated in the pathogenesis of Parkinson's disease. Although α-synuclein function is uncertain, the protein has homology to the chaperone molecule 14-3-3. In addition, α-synuclein can bind to 14-3-3, and both α-synuclein and 14-3-3 bind to many of the same proteins. Because 14-3-3 binds to and activates tyrosine hydroxylase, the rate-limiting enzyme in dopamine (DA) biosynthesis, we explored whether α-synuclein also bound to tyrosine hydroxylase and influenced its activity. Immunoprecipitation revealed an interaction between α-synuclein and tyrosine hydroxylase in brain homogenates and MN9D dopaminergic cells. Colocalization of α-synuclein with tyrosine hydroxylase was confirmed by immunoelectron microscopy. To explore the consequences of the interaction, we measured the effect of recombinant α-synuclein on tyrosine hydroxylase activity in a cell-free system and observed a dose-dependent inhibition of tyrosine hydroxylase by α-synuclein. To measure the impact of α-synuclein on tyrosine hydroxylase in dopaminergic cells, we stably transfected MN9D cells with wild-type or A53T mutant α-synuclein. Overexpression of wild-type or A53T mutant α-synuclein did not significantly alter tyrosine hydroxylase protein levels in our stably transfected cells. However, overexpressing cell lines had significantly reduced tyrosine hydroxylase activity and a corresponding reduction in dopamine synthesis. The reduction in cellular dopamine levels was not caused by increased dopamine catabolism or dopamine efflux. These data suggest that α-synuclein plays a role in the regulation of dopamine biosynthesis, acting to reduce the activity of tyrosine hydroxylase. If so, a loss of soluble α-synuclein, by reduced expression or aggregation, could increase dopamine synthesis with an accompanying increase in reactive dopamine metabolites.
609 citations
Cites methods from "Tyrosine hydroxylase. the initial s..."
...Tritiated water release from 3,5- 3H-L-tyrosine was measured using modifications of the methods of Nagatsu et al. (1964), Reinhard et al. (1986), Waymire et al. (1991), and Tanji et al. (1994)....
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TL;DR: This chapter takes a view of biogenic amines in the insect nervous system and to assess critically the evidence for their roles as neurotransmitters, neuromodulators and neurohormones.
Abstract: Publisher Summary This chapter takes a view of biogenic amines in the insect nervous system and to assess critically the evidence for their roles as neurotransmitters, neuromodulators and neurohormones. It attempts to answer several questions such as where biogenic amines are located in the insect nervous system; how are they synthesized and inactivated; and what physiological roles do they perform and how do they bring about their effects. Particular emphasis is placed on the correlation of biochemical, physiological, pharmacological and anatomical information from systems containing identified aminergic neurones. The chapter points out instances where data from one or more of the approaches is either missing or conflicts with that from another and suggests experiments to resolve these points. The function of biogenic amines in the insect nervous system has been compared with that in the vertebrate nervous system. In this context the chapter mentions the role of biogenic amines as chemical messengers in the vertebrate nervous system.
596 citations
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TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
289,852 citations
TL;DR: A modification of the naphthalene-dioxane-PPO liquid scintillator has been described which will allow up to 3.0 ml of an aqueous solution to be counted as mentioned in this paper.
7,634 citations
TL;DR: A method for chemical assay of small amounts of adrenaline and noradrenaline in tissues is described, utilizing the difference in the activation spectra of the fluoro-phores to identify the two amines.
Abstract: Summary.
A method for chemical assay of small amounts of adrenaline and noradrenaline in tissues is described. The catechol amines are extracted with perchloric acid. The extracts are passed through a cation exchange column (Dowex 50) which takes up the catechol amines. Elution of the amines from the column is performed by hydrochloric acid. Estimation of the two amines in the eluates is made fluorimetrically after oxidation and rearrangement in alkali. Differentiation between adrenaline and noradrenaline is performed by utilizing the difference in the activation spectra of the fluoro-phores.
993 citations
TL;DR: The fluorometric method is used to determine the amount of tyrosine in plasma from fasting patients with different disease states, as compared to the amountof the amino acid found in the plasma of normal fasting controls.
934 citations
TL;DR: A large number of both normally occurring and foreign compounds of an aromatic nature are hydroxylated in the animal body to yield products with phenolic properties, the pathways by which these products are produced are poorly understood, but several may be postulated.
596 citations