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

Allostery of tyrosine hydroxylase was found by kinetical studies of partially purified tyrosine hydroxylase from clonal rat pheochromocytoma PC12h cells. Positive cooperativity toward the cofactors, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin [(6R)BH4] and (6S)-L-erythro-5,6,7,8-tetrahydrobiopterin [(6S)BH4], was observed. It is indicated that biopterin might be the regulatory factor of the enzyme polymers, which changes the affinity for the cofactor itself. Moreover, the stereochemical structure of (6R)BH4, the naturally-occurring cofactor, took an important role on the kinetical properties of the enzyme in concern with L-tyrosine.
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PMID:Allosteric effect of tetrahydrobiopterin cofactors on tyrosine hydroxylase activity. 134 77

Salsolinol is one of the dopamine-derived tetrahydroisoquinolines and is synthesized from pyruvate or acetaldehyde and dopamine. As it cannot cross the blood-brain barrier, salsolinol as the R enantiomer in the brain is considered to be synthesized in situ in dopaminergic neurons. Effects of R and S enantiomers of salsolinol on kinetic properties of tyrosine hydroxylase [tyrosine, tetrahydrobiopterin:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2], the rate-limiting enzyme of catecholamine biosynthesis, were examined. The naturally occurring cofactor of tyrosine hydroxylase, L-erythro-5,6,7,8-tetrahydrobiopterin, was found to induce allostery to the enzyme polymers and to change the affinity to the biopterin itself. Using L-erythro-5,6,7,8-tetrahydrobiopterin, tyrosine hydroxylase recognized the stereochemical structures of the salsolinols differently. The asymmetric center of salsolinol at C-1 played an important role in changing the affinity to L-tyrosine. The allostery of tyrosine hydroxylase toward biopterin cofactors disappeared, and at low concentrations of biopterin such as in brain tissue, the affinity to the cofactor changed markedly. A new type of inhibition of tyrosine hydroxylase, by depleting the allosteric effect of the endogenous biopterin, was found. It is suggested that under physiological conditions, such a conformational change may alter the regulation of DOPA biosynthesis in the brain.
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PMID:Inhibition of tyrosine hydroxylase by R and S enantiomers of salsolinol, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline. 134 43

Previous reports have shown that among the markers for the nigro-striatal dopamine (DA) system measured in the striatum, dopamine uptake seems to be more severely affected than the others in the weaver mutant mouse. In the present study we examined DA levels, tyrosine hydroxylase (TH) activity, and high-affinity DA uptake to determine if the DA uptake is most affected when all the measurements are made in the same striatal homogenate in the same laboratory. We found that the DA uptake activity was most altered (93% lower) compared to DA levels (68% lower) and TH activity (64% lower). The DA uptake was so low in the weaver that we could not obtain reliable kinetic parameters. For TH activity we found that the Vmax was 36% lower while the Km for L-tyrosine was 92% higher in the weaver striatum. This lower affinity for substrate suggests that the TH enzyme itself may be altered in the nigro-striatal system of the weaver mutant mouse.
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PMID:Comparison of alterations in tyrosine hydroxylase, dopamine levels, and dopamine uptake in the striatum of the weaver mutant mouse. 135 43

Recombinant rat PC12 tyrosine hydroxylase, also called tyrosine 3-monooxygenase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2], purified from Escherichia coli is in an activated form with a low Km for the tetrahydrobiopterin cofactor and a pH optimum of 6.5. Pretreatment with low levels of the derived product, dopamine, inhibits catalytic activity, increases the Km for the cofactor, and shifts the pH curve towards a more acidic pH optimum. Labeled dopamine binds to tyrosine hydroxylase with high affinity (Kd = 1 microM) but low stoichiometry (r = 0.08 mol/mol of enzyme subunit). The binding of dopamine results in the appearance of a blue-green chromophore with lambda max at approximately 660 nm, which is consistent with the formation of a catecholamine-iron complex. In the absence of dopamine, the recombinant enzyme cannot be further activated by phosphorylation with cAMP-dependent protein kinase, although as much as 1 mol of phosphate is incorporated per mol of subunit. In contrast, the enzyme pretreated with dopamine is activated by phosphorylation in the same fashion and to the same extent as the native hydroxylase. The results suggest that the high-affinity binding of catecholamine products is a pivotal post-translational modification that determines the state of enzyme activation and the response to phosphorylation.
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PMID:Regulation of recombinant rat tyrosine hydroxylase by dopamine. 135 65

Endogenous dopamine (DA) release was measured in perfused rat retinae. Perfusion with elevated potassium (40 mM K) resulted in a 5-6-fold increase in DA release over baseline or 11.6 +/- 0.9% of final tissue DA content. When the selective DA D2 receptor agonist quinpirole was added to the perfusion medium (at 1 and 10 microM), K-stimulated DA release was significant decreased compared to controls (to 7.0 +/- 1.6 and 6.14 +/- 1.4%, respectively). Addition of the D2 antagonist (+/-)-sulpiride (10 microM) significantly increased DA release to 19.1 +/- 1.3%. DA could be released with successive pulses of K; an initial 10 min pulse resulted in a 4-5-fold increase in endogenous DA release over basal levels or 11.4% of the final retinal tissue DA content and a 3-fold increase (a 9.3% fractional release) upon a second K stimulation given 50 min later. The ratio of stimulated DA release during the two K pulses was 0.82 +/- 0.04. When L-tyrosine (100 microM) was included in the medium throughout the perfusion, K2/K1 was increased to 1.14 +/- 0.13. Both tissue DA level and release were decreased by the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (AMPT). At 10 microM AMPT K-stimulated DA release was reduced by 50% during the first pulse and completely abolished during the second K pulse. At 100 microM both basal and K-stimulated release were significantly reduced. Exposure of dark-adapted retinae to light in L-tyrosine-supplemented perfusion medium resulted in an increased release of DA compared to retinae perfused with tyrosine-free medium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tyrosine augments dopamine release in stimulated rat retina. 136 13

Changes induced by internal administration of L-tyrosine and L-phenylalanine in high-threshold calcium currents have been studied on perfused PC12 pheochromocytoma cells using whole-cell voltage-clamp technique. A method for rapid changes of perfusing solutions has been used. L-Tyrosine (20 microM) slowed down the decline ('wash-out') of ICa occurring during intracellular perfusion and in most cells induced its temporary recovery. alpha-Methyl-D,L-tyrosine (a tyrosine hydroxylase blocker) exerted a similar effect. On the other hand, L-phenylalanine (20 microM) in most cells speeded-up the decline of ICa. Replacement of ATP in the perfusing solution by an equivalent amount of ADP (2 mM) did not alter the effects of amino acids. The possible mechanisms of the described changes are discussed in connection with the known role of L-tyrosine in posttranslational modifications of microtubular proteins.
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PMID:Effects of intracellular administration of L-tyrosine and L-phenylalanine on voltage-operated calcium conductance in PC12 pheochromocytoma cells. 165 34

Changes in the high-threshold calcium current (Ica) induced by intracellular administration of L-tyrosine and L-phenylalanine have been studied on internally perfused PC 12 pheochromocytoma cells using whole-cell voltage-clamp technique. L-tyrosine (20 microM/l) not only prevented a decay of Ica occurring during intracellular perfusion but induced also its transient recovery. In contrast, L-phenylalanine (20 microM/l) accelerated a decline of Ica. Replacement of ATP in the perfusing solution by an equivalent amount of ADP (2 mmol/l) did not alter the effect of amino acids. alpha-methyl-D, L-tyrosine (a specific blocker of tyrosine hydroxylase) caused the effect similar to that of L-tyrosine.
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PMID:[Effect of intracellular administration of L-tyrosine and L-phenylalanine on voltage dependent calcium current in PC 12 pheochromocytoma cells]. 167 91

To enable us to study expression of tyrosine hydroxylase [TH; tyrosine 3-monooxygenase; L-tyrosine tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] as a measure of dopaminergic neuron function in future experiments, methods were developed to quantify TH mRNA levels in cultures of dopaminergic mesencephalic cells. The model of selective dopaminergic toxicity of 1-methyl-4-phenylpyridinium (MPP+) was used to verify the specificity of our methods. Fetal (embryonic day 15) rat ventral mesencephalic cell cultures were treated with 15 microM MPP+ for 48 h, conditions previously shown to reduce the number of TH-immunoreactive neurons, TH activity, and dopamine uptake to 5-10% of control values. This treatment decreased the number of neurons labeled by TH in situ hybridization to 9% of untreated controls and caused a strong reduction of the abundance of TH mRNA in Northern blots. Our findings establish TH mRNA expression as a parameter for future studies of toxic and trophic effects on cultured dopaminergic neurons, and they support the view that MPP+ destroys dopaminergic neurons.
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PMID:Tyrosine hydroxylase mRNA expression by dopaminergic neurons in culture: effect of 1-methyl-4-phenylpyridinium treatment. 167 30

The distribution of acidic (aFGF) and basic (bFGF) fibroblast growth factor mRNA and protein were examined in mesencephalon by immunohistochemistry, immunoblot analysis, in situ hybridization histochemistry, and RNA analysis. Coexistence of aFGF or bFGF with tyrosine hydroxylase protein in nigral cells was observed with immunohistochemistry. Both aFGF and bFGF mRNAs were found in the substantia nigra. Unilateral 6-hydroxydopamine lesions of nigrostriatal neurons resulted in a loss of aFGF and tyrosine hydroxylase [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] mRNA-positive neurons on the lesioned side. The distribution of aFGF mRNA in monkey brain was similar to that seen in the rat. RNA and immunoblot analysis confirmed the presence of both aFGF and bFGF mRNAs and proteins in the substantia nigra of rat, monkey, and human.
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PMID:Expression of acidic and basic fibroblast growth factors in the substantia nigra of rat, monkey, and human. 171 52

Incubation of bovine chromaffin cells with L-[14C]phenylalanine resulted in label accumulation in catecholamines at about 30% of the rate seen with L-tyrosine as precursor. Studies with purified tyrosine hydroxylase (EC 1.14.16.2) showed that the enzyme catalysed the hydroxylation of L-phenylalanine first to L-p-tyrosine and then to 3,4-dihydroxyphenylalanine (DOPA). No evidence for a significant involvement of an L-m-tyrosine intermediate in DOPA formation was found.
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PMID:Phenylalanine as substrate for tyrosine hydroxylase in bovine adrenal chromaffin cells. 197 34


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