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)

Endogenous cytochrome oxidase activity was investigated in the adult rat striatum at the light microscope level to see if it was distributed in accordance with the established striatal patch/matrix compartmentalisation. Striatal sections stained to visualise cytochrome oxidase activity were compared with serial sections stained to visualise tyrosine hydroxylase and calbindinD28k-like immunoreactivity, established markers of the matrix compartment. The distribution of endogenous cytochrome oxidase activity was found to coincide with the immunocytochemical staining pattern seen for tyrosine hydroxylase and calbindinD28k whereby areas of intense tyrosine hydroxylase and calbindinD28k-like immunoreactivity (termed the matrix) corresponded to areas of intense cytochrome oxidase activity. Conversely, areas of less intense tyrosine hydroxylase and calbindinD28k-like immunoreactivity (termed patches) corresponded to areas of low cytochrome oxidase activity. In addition, the distribution of two other oxidative enzymes involved in the regulation of mitochondrial respiration, succinic dehydrogenase and NADH-diaphorase, was examined in the striatum and substantia nigra by using histochemical techniques. Both NADH-diaphorase and succinic dehydrogenase histochemistry showed an uneven pattern of neuropil staining in the striatum. In the substantia nigra a few intensely stained cell bodies were seen in the dorsal-lateral tip of the pars reticulata with both histochemical techniques. By using an anti-cytochrome oxidase antibody an abundance of immunoreactive cell bodies and processes were seen in the substantia nigra, particularly in the dorso-medial rim and dorsal tip of the pars reticulata. The substantia nigra pars lateralis contained many intensely stained cytochrome oxidase-like immunoreactive cell bodies and processes.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Compartmental distribution of cytochrome oxidase in the striatum of the rat. 134 42

The aim of modern Parkinson therapy is to overcome the dopamine deficit in the brain of parkinsonian patients which is the cause of their motor disability. This can be achieved in two ways: (a) substitution of the lacking dopamine by l-dopa, or (b) stimulation of the endogenous biosynthesis by activating the enzyme tyrosine hydroxylase. The latter approach is possible by the iron compound oxyferriscorbone or by the coenzyme nicotinamide adenine dinucleotide (NADH). In addition to these two major medications the essential therapeutic additives such as the decarboxylase inhibitor benserazide, the monoamineoxidase B inhibitor deprenyl and the dopamine receptor agonist lisuride should be used for the fine adjustment of the individual patient.
 ...
PMID:Strategy and tactic of modern Parkinson therapy. 269 35

The substrates of dihydropteridine reductase (EC 1.6.99.7), quinonoid 7,8-dihydro(6 H)pterins, are unstable and decompose in various ways. In attempting to prepare a more stable substrate, 6,6,8-trimethyl-5,6,7,8-tetrahydro(3 H)pterin was synthesised and the quinonoid 6,6,8-trimethyl-7,8-dihydro(6 H)pterin derived from it is extremely stable with a half-life in 0.1 M Tris/HCl (pH 7.6, 25 degrees C) of 33 h. Quinonoid 6,6,8-trimethyl-7,8-dihydro(6 H)pterin is not a substrate for dihydropteridine reductase but it is reduced non-enzymically by NADH at a significant rate and it is a weak inhibitor of the enzyme: I50 200 microM, pH 7.6, 25 degrees C when using quinonoid 6-methyl-7,8-dihydro(6 H)pterin as substrate. 6,6,8-Trimethyl-5,6,7,8-tetrahydropterin is a cofactor for phenylalanine hydroxylase (EC 1.14.16.1) with an apparent Km of 0.33 mM, but no cofactor activity could be detected with tyrosine hydroxylase (EC 1.14.16.2). Its phenylalanine hydroxylase activity, together with the enhanced stability of quinonoid 6,6,8-trimethyl-7,8-dihydro(6 H)pterin, suggest that it may have potential for the treatment of variant forms of phenylketonuria.
 ...
PMID:Reduced 6,6,8-trimethylpterins. Preparation, properties and enzymic reactivities with dihydropteridine reductase, phenylalanine hydroxylase and tyrosine hydroxylase. 285 23

A rapid and simple simultaneous micropurification procedure of tyrosine hydroxylase (TH) and dihydropteridine reductase (DPR) was developed from soluble supernatants of 1 to 2 g of rat adrenal gland or caudate nucleus. All purification procedures for the two enzymes were complete within 3 days. The recovery of TH and DPR was reproducible and approximately 20 and 40%, respectively. Purification procedure for TH involved chromatographies with DEAE-Sephacel, Bio-Gel A-1.5 m, and heparin-Sepharose. As judged by gel filtration and sodium dodecyl sulfate-gel electrophoresis, the enzyme purified from each tissue appeared to be homogeneous and was composed of an identical subunit, each possessing a Mr of 60,000. With DEAE-Sephacel column chromatography, TH was separated completely from DPR. DPR was purified by subsequent chromatographies with Sephadex G-50 and blue Sepharose to a purity of 50%. DPR in adrenals and brain was found to be a NADH-dependent type. This micropurification procedure is applicable to assessing the molecular properties of TH modified physiologically or pharmacologically in vivo, and to getting a small amount of the pure enzyme as antigen for producing its antibody.
 ...
PMID:Simultaneous simple purification of tyrosine hydroxylase and dihydropteridine reductase. 613 72

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.
 ...
PMID:Enzymatic stimulation and enzymatic inhibition in Parkinson's disease. 810 11

The activity of the tyrosine hydroxylase, the enzyme which is diminished in the brains of Parkinson patients, has been measured in cultured PC 12 rat phaeochromocytoma cells. In the same way dopamine content in the medium after incubating these cells with or without NADH was assayed. The experiment shows that NADH is able to increase the activity of the tyrosine hydroxylase and dopamine - production in PC 12 cells up to 6 times. The results provide evidence that NADH is able to stimulate dopamine - biosynthesis directly.
 ...
PMID:Stimulation of dopamine biosynthesis in cultured PC 12 phaeochromocytoma cells by the coenzyme nicotinamide adeninedinucleotide (NADH). 810 44

Neurons in the human adrenal medulla, stained by the NADH-diaphorase reaction, were counted and their neurochemical markers were investigated by double labeling immunofluorescence with special reference to substance P. The findings indicate a significant participation of intramedullary nerve cell bodies in human adrenal innervation with 40.4 neurons/mm3 adrenal medulla. Substance P-immunoreactive neurons, which made up approximately 20% of all neurons, exhibited heterogeneity by co-localization of immunoreactivities for dynorphin, for cholecystokinin, and for neurofilament triplet. Substance-P-immunolabeled neurons were always nonreactive for calcitonin gene-related peptide, for vasoactive intestinal polypeptide, or for tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis. These chemical phenotypes of intramedullary neurons reveal immunohistochemical similarities with postganglionic neurons in parasympathetic ganglia or with enteric neurons, suggesting a hitherto unrecognized functional significance of the intrinsic nervous system in the human adrenal gland.
 ...
PMID:Immunohistochemical heterogeneity of nerve cells in the human adrenal gland with special reference to substance P. 860 96

Exogenous application of levodopa is conventionally used to equalize the striatal dopamine deficit in idiopathic Parkinson's disease (PD). The stimulation of endogenous biosynthesis of levodopa via activation of tyrosine hydroxylase (TH) has been proposed as new therapeutic concept in PD. This may be achieved by exogenous supply with the reduced coenzyme nicotinamide adenine dinucleotide (NADH). Aim of this open prospective study was to investigate (1) the efficacy of a new developed, parenteral application form of NADH on Parkinsonian symptoms and (2) the influence of bioavailability of levodopa. 15 patients, suffering from idiopathic PD (11 male, 4 female, age: 61.40[mean] +/- 10.27[SD] range: 44-74 years, Hoehn and Yahr stage: 3.03 +/- 0.69, range 2-4) received intravenous infusions of NADH (10 mg a' 30 min) over a period of 7 days in addition to conventional Parkinsonian pharmacotherapy. Parkinsonian symptoms were scored before (day 1) and after NADH treatment (day 8). Levodopa plasma levels were estimated over a period of four hours on the day before and on the first day of NADH application by HPLC. Parkinsonian patients showed a significant response, evaluated by the Unified Parkinson's Disease Rating Scale Version 3.0 (p = 0.025; Wilcoxon test). Moreover application of NADH significantly increased bioavailability of plasma levodopa (AUC, p = 0.035; Cmax p = 0.025). In conclusion NADH in used galenic form may be a potent stimulator of endogenous levodopa biosynthesis with clinical benefit for Parkinsonian patients.
 ...
PMID:Parenteral application of NADH in Parkinson's disease: clinical improvement partially due to stimulation of endogenous levodopa biosynthesis. 901 5

Treatment of Parkinson patients with L-DOPA (3,4-dihydroxy-L-phenylalanine) leads to endproduct inhibition of tyrosine hydroxylase, the key enzyme in dopamine biosynthesis and the enzyme needing tetrahydrobiopterin and iron as cofactors. To overcome this problem an alternative treatment was investigated which attempted to stimulate endogenous dopamine biosynthesis. Incubation of rat PC 12 cells with NADH (beta-nicotinamide adeninedinucleotide) leads to increased dopamine production. We investigated the possibility that this increase of dopamine biosynthesis was due to stimulation of quinonoid dihydropteridine reductase, the enzyme which recycles the inactive dihydrobiopterin to the active tetrahydrobiopterin. The experiments showed that whereas NADH is able to increase dopamine production in PC 12 cells (rat phaeochromocytoma cells, clone PC 12) up to three-fold, no influence is exerted by NADH on pteridine metabolism; neither are tetrahydrobiopterin concentrations nor the de novo-biosynthesis of pteridines from guanosine triphosphate altered by NADH. Further no influence of NADH on protein de novo synthesis of quinonoid dihydropteridine reductase was observed. However, NADH was able to directly increase the catalytic activity of this enzyme. Our results suggest that the stimulation of dopamine biosynthesis by NADH is due to more rapid regeneration of quinonoid dihydrobiopterin to tetrahydrobiopterin.
 ...
PMID:NADH stimulates endogenous dopamine biosynthesis by enhancing the recycling of tetrahydrobiopterin in rat phaeochromocytoma cells. 924 90

Enteric neurons have distinct neurochemical codings in each species. The basal tone of the gastrointestinal tract of the rabbit is low and produces neurally evoked pendular movements. Therefore, it might have an innervation pattern different from that of other laboratory animals. We have characterised myenteric neuron populations in rabbit ileum with neurochemical markers that are known to be associated with distinct cell types and/or fibre systems in the myenteric plexus. The density of nerve cells estimated with the NADH-diaphorase technique was about 2500 cells/cm2 and most, if not all, neurons contained microtubule-associated protein 2. NADPH-diaphorase-positive cells were numerous. One cell type was large and emitted long straight processes, whereas small cells bore thin filamentous dendrites. Neurons immunoreactive for 28-kDa calcium-binding protein were rare. Over 70% of them had very strongly labelled lamellar dendrites. Their axons were beaded and formed pericellular baskets around unstained somata. We found very few small tyrosine-hydroxylase-positive cells. The fibre network in the plexus was very strong; the axons formed many pericellular baskets. In double labelling studies, no co-localisation was revealed between the 28-kDa calcium-binding protein and NADPH-diaphorase. Some fibres containing 28-kDa calcium-binding protein formed only a few contacts on somata of NADPH-diaphorase-positive cells. None of the NADPH-diaphorase-labelled cells were found to be stained for tyrosine hydroxylase. Tyrosine-hydroxylase-positive fibres rarely made pericellular baskets on the surface of NADPH-diaphorase-positive somata. Strongly immunolabelled pericellular baskets were never observed around NADPH-diaphorase-positive cell somata. The results suggest that myenteric neurons in rabbit comprise distinct and characteristic neurochemical properties that are different from the rodent pattern. Therefore, the explanation of the motility pattern of rabbit intestine can be approached on a chemical neuroanatomical basis.
 ...
PMID:Some neurohistochemical properties of nerve elements in myenteric plexus of rabbit ileum: similarities and dissimilarities to the rodent pattern. 956 Apr 71


1 2 3 Next >>