Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ventral mesencephalons of hamster, guinea pig, cat, monkey, and several humans with and without the diagnosis of schizophrenia were analyzed with in situ hybridization and immunohistochemistry. Extensive codistribution of cholecystokinin mRNA and tyrosine hydroxylase [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] mRNA was observed in cats and monkeys as well as in all five human subjects with the diagnosis of schizophrenia and in two out of five control brains. Double labeling revealed coexistence of the two markers in cat, monkey, and human. No cholecystokinin mRNA or cholecystokinin peptide was detected in the substantia nigra/ventral tegmental area of the hamster or guinea pig, even after acute and chronic neuroleptic treatment.
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PMID:Analysis of expression of cholecystokinin in dopamine cells in the ventral mesencephalon of several species and in humans with schizophrenia. 197 24

In cultured cells of the Bomirski Ab amelanotic hamster melanoma line, the substrates of tyrosinase, L-tyrosine, and L-DOPA induce the melanogenic pathway. In this report, we demonstrate that these substrates regulate the subcellular apparatus involved in their own metabolism and that this regulation is under the dynamic control of one of the components of this apparatus, tyrosinase, via tyrosine hydroxylase activity. Culturing cells with nontoxic but melanogenically inhibitory levels of phenylthiourea (PTU; 100 microM) strongly inhibits induction of both the tyrosine hydroxylase and DOPA oxidase activities of tyrosinase by L-tyrosine (200 microM) but has no effect on the induction of either activity by L-DOPA (50 microM). De novo synthesis of premelanosomes precedes the onset of tyrosine-induced melanogenesis. Thereafter, increases in the population of melanosomes (likewise inhibited by PTU) correlate positively with increases in tyrosinase activity induced by L-tyrosine. Melanogenesis induced by L-DOPA in the absence of L-tyrosine is rate-limited not by tyrosinase but by inadequate melanosome synthesis. Our findings indicate that in Bomirski Ab amelanotic hamster melanoma cells the synthesis of the subcellular apparatus of melanogenesis is initiated by L-tyrosine and is regulated further by tyrosinase and L-DOPA, which serves as a second messenger subsequent to tyrosine hydroxylase activity.
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PMID:L-tyrosine, L-dopa, and tyrosinase as positive regulators of the subcellular apparatus of melanogenesis in Bomirski Ab amelanotic melanoma cells. 249 48

Fifteen years ago epinephrine cells were shown to be present in the medulla oblongata of the rat. These cell groups (C1 and C2) were thought to supply the epinephrine innervation in the rest of the central nervous system. In this study I demonstrate the presence of epinephrine-producing neurons in the forebrain of the young rat. Neurons that are immunopositive for phenylethanolamine N-methyltransferase (S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.29) are present in the central nucleus of the amygdala as well as in the bed nucleus of the stria terminalis. Neurons in the same location are also immunopositive for tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydrobiopterine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2]. The phenylethanolamine N-methyltransferase immunopositivity disappears by day 35, while a small amount of tyrosine hydroxylase-positive cells still can be found in the adult. In situ hybridization reveals tyrosine hydroxylase mRNA in the above nuclei in both young and adult animals. The number of the positive cells decreases in adulthood. RNA blot-hybridization analysis showed the presence of phenylethanolamine N-methyltransferase mRNA in the amygdala and the bed nucleus of the stria terminalis in the young and in the adult rat brain. Neurons that are immunopositive for phenylethanolamine N-methyltransferase are also present in the human amygdala.
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PMID:Phenylethanolamine N-methyltransferase-containing neurons in the limbic system of the young rat. 256 64

Tyrosine is the precursor of catecholamines. Small doses of tyrosine produce tachycardia and hypertension while higher doses produce bradycardia and hypotension in anaesthetised rats. The mechanism of these effects has not been established. An increased synthesis and release of catecholamines has been suggested to be the mechanism. Various pretreatments were given to anaesthetised Wistar rats to study the influence of a blockade of L-tyrosine metabolism and thus a blockade of catecholamine synthesis, on these cardiovascular effects: valine, which inhibits tyrosine uptake into brain, alpha-methyl-p-tyrosine, which blocks the rate-limiting enzyme, tyrosine hydroxylase, carbidopa and benserazide, which both inhibit dopa decarboxylase, and desipramine, which blocks catecholamine re-uptake. Benserazide and alpha-methyl-p-tyrosine partially blocked the stimulatory effects of tyrosine. None of the pretreatments were able to block effectively the inhibitory effects of L-tyrosine. Therefore, the metabolism of tyrosine to form catecholamines may be involved in the stimulatory but not in the inhibitory cardiovascular effects of L-tyrosine. Valine pretreatment did not antagonize the depressant effects of tyrosine. Since valine blocks the uptake of L-tyrosine into the brain, the depressant effects of L-tyrosine might be peripheral rather than central in origin.
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PMID:Cardiovascular effects of L-tyrosine: influence of blockade of tyrosine metabolism. 256 1

A cDNA clone encoding the complete sequence of an active rat choline acetyltransferase (ChoAcTase; acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6) has been isolated. Analysis of the deduced amino acid sequence reveals 85% and 31% identity with the porcine and Drosophila melanogaster enzymes, respectively. To further elucidate the molecular basis of neurotransmitter-related phenotypic plasticity, the expression of ChoAcTase mRNA was compared with that of tyrosine hydroxylase [TH; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2], in neurons from superior cervical ganglia grown in the following conditions: 1) normal medium, 2) high K+ medium, and 3) normal medium supplemented with 50% muscle-conditioned medium (CM). TH mRNA was expressed in all three media; its level rose in high K+ and decreased strikingly in the presence of CM. ChoAcTase mRNA could be visualized in CM, but fell to undetectable levels in normal and high K+ media. These results suggest that translational or post-translational mechanisms do not play a major role for the modulation of neurotransmitter-associated phenotype.
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PMID:Complete sequence of a cDNA encoding an active rat choline acetyltransferase: a tool to investigate the plasticity of cholinergic phenotype expression. 257 Jan 61

Rat fibroblasts were infected with a retroviral vector containing the cDNA for rat tyrosine hydroxylase [TH; tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2]. A TH-positive clone was identified by biochemical assay and immunohistochemical staining. When supplemented in vitro with pterin cofactors required for TH activity, these cells produced L-dopa and released it into the cell culture medium. Uninfected control cells and fibroblasts infected with the TH vector were grafted separately to the caudate of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. Only grafts containing TH-expressing fibroblasts were found to reduce rotational asymmetry. These results have general implications for the application of gene therapy to human neurological disease and specific implications for Parkinson disease.
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PMID:Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease. 257 72

Several clones specific for tyrosine hydroxylase [tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] have been identified from a rat PC12 library by using the previously characterized clone pTH-1. The most complete of these, pTH-51, is 1758 base pairs long and covers most of the length of the mRNA, including the entire coding and 3' untranslated region. The polypeptide has an estimated molecular weight of 55,903 and some of its characteristic features are discussed.
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PMID:Complete coding sequence of rat tyrosine hydroxylase mRNA. 285 92

Tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase; L-tyrosine,tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and phenylethanolamine N-methyltransferase, EC 2.1.1.28) are involved in catecholamine biosynthesis and are considered soluble proteins. However, they may actually be localized on the surface of the chromaffin granule. We have used the detergent digitonin to permeabilize the plasma membrane of cultured adrenal chromaffin cells to investigate the subcellular localization of TyrOHase and PMTase. A digitonin titration of the release of proteins and catecholamines revealed the existence of at least three subcellular compartments that are distinguished by their digitonin sensitivity: (i) soluble proteins, which were released upon treatment of the cells with low digitonin concentrations (5 microM), (ii) a "digitonin-sensitive" cytoplasmic protein pool, which required higher concentrations of digitonin for release (10 microM) and included TyrOHase and PMTase, and (iii) the chromaffin granule, which was insensitive to digitonin. Analysis of the rates of release of all of these proteins revealed that the rate of TyrOHase and PMTase release was slower at 10 microM than at 40 microM digitonin, while the rates of release of the other proteins were similar at both concentrations and varied in proportion to their respective sizes. Treatment with cytoskeletal disrupting agents had no effect on TyrOHase or PMTase efflux. These data suggest that TyrOHase and PMTase are in a detergent-labile association in the cell. This is consistent with the concept that TyrOHase and PMTase may be localized on the surface of the chromaffin granule.
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PMID:Restricted diffusion of tyrosine hydroxylase and phenylethanolamine N-methyltransferase from digitonin-permeabilized adrenal chromaffin cells. 287 56

We report here the isolation of a cDNA clone containing the full coding region of bovine phenylethanolamine N-methyltransferase (PNMTase, EC 2.1.1.28, S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase). The complete nucleotide sequence of the cDNA has been determined, and the amino acid sequence of PNMTase deduced. Cultured cells transfected with an expression vector containing this cDNA produced high levels of PNMTase enzymatic activity. Antibodies specific for tyrosine hydroxylase [EC 1.14.16.2, tyrosine 3-monooxygenase; L-tyrosine, tetrahydrobiopterine: oxygen oxidoreductase (3-hydroxylating)], the first enzyme in the catecholamine pathway, possess a striking affinity for the PNMTase protein synthesized in vitro. Comparison of the deduced amino acid sequence of bovine PNMTase to rat tyrosine hydroxylase reveals that PNMTase shares significant homology with tyrosine hydroxylase and supports previous protein and immunological data suggesting that the catecholamine biosynthetic enzymes are structurally related.
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PMID:Complete nucleotide and deduced amino acid sequence of bovine phenylethanolamine N-methyltransferase: partial amino acid homology with rat tyrosine hydroxylase. 287 53

Tyrosine hydroxylase [TyrOHase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2], an essential enzyme in the synthesis of catecholamines, is expressed normally by neurons in the brainstem but not by those in mature neocortex. When embryonic neocortex is transplanted into adult neocortex, TyrOHase-immunoreactive cells develop and continue to be present in the transplants for the life of the host animal. The percentage of transplant neurons that express TyrOHase is highly correlated with the age of the embryonic donor tissue at the time of transplantation. Many TyrOHase-immunoreactive cells are present in transplants from embryonic day 12 (E12) embryos. The labeled cells are frequently arrayed in striking clusters of cell bodies and their processes, which ramify densely within the transplants. Moderate numbers of cells are found scattered throughout transplants from E14 donors, while E17 donors consistently develop small numbers of TyrOHase-containing cells. Tissue removed for transplantation on the day before birth (E19) never contains cells that express TyrOHase. The TyrOHase-positive cells are mostly bipolar and stellate in shape and show neither immunoreactivity for other catecholamine-synthesizing enzymes nor catecholamine fluorescence. These results provide a demonstration of continued TyrOHase synthesis in central nervous system cells that normally do not express this enzyme. Because of these and similar results with other neurotransmitter enzymes, the transplantation paradigm is particularly useful as a technique for studying the factors that regulate enzyme induction and activity during development of the nervous system.
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PMID:Tyrosine hydroxylase is expressed by neocortical neurons after transplantation. 287 27


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