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 central nervous system of the mollusc Helix pomatia, like that of other molluscs, contains a very high level of dopamine. However, noradrenaline is weakly represented. These characteristics apply to the peripheral nervous system and more particularly to the heart. The study of the phenomena taking part in the synthesis and inactivation of catecholamines shows that these processes are not different in vertebrates and molluscs. Thus, in the particular case of Helix pomatia the synthesis of catecholamines is carried out by tyrosine hydroxylase, aromatic amino acid decarboxylase and dopamine-beta-hydroxylase. These enzymes are not only active in the ganglia and nerves, but also in the peripheral nervous system. The monoamines are associated with granules. The synthesized enzymes in the pericarya migrate due to the axonal flow and accumulate in the intracardiac nerve endings. In Helix pomatia, the enzymes participate actively in the local synthesis of catecholamines using the precursors tyrosine and DOPA. We have little information on the uptake of dopamine by nervous structures, but it would seem that this phenomenon seems to play an active role in the synaptic inactivation of dopamine. The glial elements also play a part in uptake and inactivation. In most species the nervous system has very little monoamine oxidase, and there is even less in the heart. The enzymic activity depends on substrates and is more active with dopamine than with 5-hydroxytryptamine. The exact localization of monoamine oxidase in the tissues is unknown. However, we believe that it plays a part in the neuronal regulation of dopamine levels and in its synaptic inactivation. The same applies for catechol O-methyltransferase.
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PMID:[The monoamines in molluscs. I. Catecholamines: biosynthesis, disposition and inactivation (author's transl)]. 4 29

The precursors tyrosine and tryptophan as well as the synthesizing and deaminating enzymes of catecholamines have been identified in methylcholanthrene-induced prostatic carcinoma of rats. Tyrosine hydroxylase, monoamine oxidase, catechol O-methyltransferase, dopamine, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid seemed to be neoplastic in origin, since electron microscopic studies failed to reveal the presence of any neuronal elements in this squamous epithelial cell carcinoma. Castration of rats significantly reduced the activity of tyrosine hydroxylase and the levels of tyrosine, dopamine, tryptophan, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid in prostate tumors. The changes appeared to be androgen specific since reintroduction of testosterone restored several of these biochemical parameters virtually to control limits. Chemical sympathectomy induced by 6-hydroxydopamine failed to alter monoamine metabolism; however, the prostatic tumor grown in 6-hydroxydopamine-treated rats showed significantly (32%) less necrosis than those grown in normal animals.
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PMID:Effect of testosterone and 6-hydroxydopamine treatment on the metabolism of catecholamine and 5-hydroxytryptamine in methylcholanthrene-induced prostate carcinoma of rats. 48 61

Two strains of Mus musculus musculus, C57BL/6J and CD-1, and Mus musculus poschiavinus, the tobacco mouse, were used to study the effects of increased gene dosage of mouse chromosome 16 (MMU 16). A developmental delay has been found in the brains of murine trisomy 16 (Ts16) fetuses. Both the brain weight (in all three strains) and DNA content (in CD-1) were reduced, while protein content was unchanged in Ts16 compared to normal littermates. The daily increments of weight and protein (except in M. m. poschiavinus) were significantly greater in Ts16. The activities of choline acetyltransferase and acetylcholinesterase and muscarinic receptor binding were reduced. Their daily increments were also reduced to less than 56% that of littermates in Ts16 brains. The rate limiting enzymes of catecholaminergic neurons, tyrosine hydroxylase and dopamine beta-hydroxylase, and the concentration of catecholamines in the brains of Ts16 animals were lower. The activities of three other catecholaminergic enzymes, DOPA decarboxylase, catechol O-methyltransferase, and monoamine oxidase, were generally elevated in Ts16 brain, as were their daily increments. These observations indicate a significant developmental alteration in the maturation of the trisomic brain and suggest future avenues for defining the effect of increased gene dosage of MMU 16 in the CNS.
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PMID:Neurochemical changes in murine trisomy 16: delay in cholinergic and catecholaminergic systems. 614 55

In order to supplement the deficient catecholamine neurotransmitters, dopamine and noradrenaline, in parkinsonian brains, the following strategies have been tried: (1) the precursor amino acids, L-DOPA and L-threo-dihydroxyphenylserine (DOPS), (2) 6R-L-erythro-tetrahydrobiopterin (BPH4) as tyrosine hydroxylase (TH) cofactor and nicotinamide adenine dinucleotide (NADH) as cofactor of dihydropteridine reductase to stimulate TH, (3) brain transplant of TH-containing cells, (4) inhibitors of monoamine oxidase (MAO) and/or catechol O-methyltransferase (COMT) with or without L-DOPA or L-DOPS, and (5) dopamine receptor agonists. Among these strategies, the precursor, L-DOPA, L-DOPS, MAO and COMT inhibitors, and dopamine receptor agonists have proved to be clinically effective. As a new strategy, increase in deficient TH activity has been tried experimentally and clinically either by stimulation of residual TH activity by the cofactors, BPH4 or NADH, or by brain transplant of natural TH-containing cells (fetal substantia nigra) or genetically engineered TH-containing cells.
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PMID:Enzymatic stimulation and enzymatic inhibition in Parkinson's disease. 810 11

The "wearing-off" phenomenon is a clinically recognized adverse effect of long-term L-DOPA therapy in Parkinson's disease. Several causes of this phenomenon have been proposed, but no direct evidence has yet been obtained. The present study was therefore conducted to investigate the effects of long-term L-DOPA administration on the dopamine system. We examined in rats the time course of the levels of L-DOPA and its metabolites in the serum and striatum, the activities of tyrosine hydroxylase and catechol O-methyltransferase, and the D1 and D2 dopamine receptor bindings in the striatum until 12 h after the final dose on the 28th day of repeated oral L-DOPA administration, and compared the results with those after a single L-DOPA administration. The results revealed that long-term L-DOPA administration induced (1) acceleration of DOPA absorption at the gut and the blood-brain barrier, (2) reduction of dopamine retention in the striatum, and (3) loss of "supersensitive response" of dopamine receptors. "Supersensitive response" induced by single L-DOPA administration was preceded by the increase of D1 messenger RNA. We suggest that these changes after long-term L-DOPA administration are causes of the "wearing-off" phenomenon in Parkinson's disease.
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PMID:Repeated L-dopa administration reduces the ability of dopamine storage and abolishes the supersensitivity of dopamine receptors in the striatum of intact rat. 838 61

1-methyl-4-phenyl-1,2,4,6,-tetrahydropyridine (MPTP) is a selective neurotoxin that produces striatal dopamine depletion resulting in parkinsonism like symptoms in humans and is, therefore, used to generate animal models for Parkinson's disease (PD). In this study, C57BL/6N mice were treated with MPTP acutely (3x20 mg/kg, 2-hour interval, one day injection). Mice were then sacrificed 24 hours after the last injection and brain tissue was collected for analysis. Significant decrease of striatal dopamine (DA) and the metabolites (DOPAC, HVA) was observed after MPTP treatment. MPTP also reduced protein expression of tyrosine hydroxylase (TH) in the striatum. Real time RT-PCR was used to examine selective genes of the dopaminergic system in the substantia nigra. Our data demonstrated that MPTP significantly decreased gene expression of TH, dopamine transporter (DAT), and vesicle monoamine transporter (VMAT), coinciding with the pattern of dopamine concentration changes and protein expression after MPTP treatment. Although a significant decrease of DA metabolites was observed in striatum, there was no change in the expression of monoamine oxidases (MAO-A, MAO-B) or catechol O-methyltransferase (COMT), indicating that these changes might be simply a consequence of reduced monoamine levels. In addition, gene expression of alpha-synuclein was also decreased with MPTP treatment, but there was no change in beta-synuclein and parkin. This is the first study using real-time PCR to indicate that MPTP selectively alters gene expression and provides information for clinical studies in PD. Future studies will focus on gene expression of other pathways that may be affected by MPTP treatment and investigation of gene expression in specific cell types in vivo using LCM technology.
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PMID:Selective alterations of gene expression in mice induced by MPTP. 1549 5

Many neurobiochemical studies show abnormalities within dopaminergic neuropathways, particularly altered dopamine transmission in etiopathogenesis of mental disorders. Evaluation of genes associated with the dopaminergic system include five well known subtypes of dopaminergic receptors, dopamine transporter and enzymes associated with the synthesis and degradation of dopamine, such as tyrosine hydroxylase, dopa decarboxylase, monoamine oxidase (MAO) and catechol O-methyltransferase (COMT). None of these genes is 'a' pathognomonic factor of schizophrenia onset. In each sequence of the following genes 'a' functional polymorphism can occur. The polymorphisms of genes MAO-A and COMT have been described in relation to various expression or altered activity of these enzymes, their influence on cognitive functions, affective and anxiety disorders, learning disabilities, aggressive behaviour, eating disorders or gender differences.
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PMID:[Genetic polymorphism of COMT in mental disorders]. 1804 78

Biosynthesis and metabolism of serotonin and catecholamines involve at least eight individual enzymes that are mainly expressed in tissues derived from the neuroectoderm, e.g., the central nervous system (CNS), pineal gland, adrenal medulla, enterochromaffin tissue, sympathetic nerves, and ganglia. Some of the enzymes appear to have additional biological functions and are also expressed in the heart and various other internal organs. The biosynthetic enzymes are tyrosine hydroxylase (TH), tryptophan hydroxylases type 1 and 2 (TPH1, TPH2), aromatic amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DbetaH), and phenylethanolamine N-methyltransferase (PNMT), and the specific catabolic enzymes are monoamine oxidase A (MAO-A) and catechol O-methyltransferase (COMT). For the TH, DDC, DBH, and MAOA genes, many single nucleotide polymorphisms (SNPs) with unknown function, and small but increasing numbers of cases with autosomal recessive mutations have been recognized. For the remaining genes (TPH1, TPH2, PNMT, and COMT) several different genetic markers have been suggested to be associated with regulation of mood, pain perception, and aggression, as well as psychiatric disturbances such as schizophrenia, depression, suicidality, and attention deficit/hyperactivity disorder. The genetic markers may either have a functional role of their own, or be closely linked to other unknown functional variants. In the future, molecular testing may become important for the diagnosis of such conditions. Here we present an overview on mutations and polymorphisms in the group of genes encoding monoamine neurotransmitter metabolizing enzymes. At the same time we propose a unified nomenclature for the nucleic acid aberrations in these genes. New variations or details on mutations will be updated in the Pediatric Neurotransmitter Disorder Data Base (PNDDB) database (www.bioPKU.org).
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PMID:Mutations in human monoamine-related neurotransmitter pathway genes. 1844 57