Kinetic properties of tyrosine hydroxylase purified from bovine adrenal medulla and bovine caudate nucleus

Oka, Koichiro; Ashiba, Gaku; Sugimoto, Takashi; Matsuura, Shinya; Nagatsu, Toshiharu

doi:10.1016/0167-4838(82)90486-1

Cited by 60 publications

(18 citation statements)

References 24 publications

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“…The K,,, values for L-tyrosine ranged from -100 to -250,uM, those for B-MPH4 being from -180 to -250 PM. The K, values for L-tyrosine are similar to those obtained from the purified rat [20] and bovine [21] enzymes. The low-affinity form of TH to pteridine (Km -200 PM) reportedly changes to the high-affinity form (K,,, -2OpM) through protein phosphorylation [22,23].…”

Section: Assay Of Th Activitysupporting

confidence: 65%

Expression of four types of human tyrosine hydroxylase in COS cells

et al. 1988

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Alternative splicing from a single gene produces four kinds of human tyrosine hydroxylase (types l-4), which have structural diversity only in the N-terminal region. We attempted expression of the type l-4 enzymes in COS cells and performed kinetic analyses. All had enzymatic activities. The K, values of the four types for L-tyrosine and 6-methyl-5,6,7,8-tetrahydropteridine were similar, although their relative homospecific activities were clearly different. The type 1 enzyme displayed the highest activity.

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Section: Assay Of Th Activitysupporting

confidence: 65%

Expression of four types of human tyrosine hydroxylase in COS cells

et al. 1988

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“…1 7 Since tyrosine hydroxylase, the rate-limiting enzyme for DA synthesis, requires molecular oxygen, a complete ischemia would reduce the synthesis of DA. The high affinity of tyrosine hydroxylase for oxygen, 18 however, may leave the brain aloof from the lack of the substrate, molecular oxygen. In addition, the increase in cyclic AMP observed in ischemic brain 19 -M would activate tyrosine hydroxylase through cAMP-dependent protein-kinase.…”

Section: Cortex Deep Grey Brainstemmentioning

confidence: 99%

Effect of ischemia on hydroxylase cofactor (tetrahydrobiopterin) and monoamine neurotransmitters in rat brain.

Iijima¹,

Hara²,

Suga³

et al. 1986

Stroke

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SUMMARY Hydroxylase cofactor, monoamine neurotransmitters and their metabolites were measured in ischemic rat brain produced by four-vessel occlusion for 30 and 60 min periods. Slight reduction of hydroxylase cofactor activity was observed in the ischemic cortex after 60 min. Dopamine increased in the brainstem, and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanlllic acid, increased throughout the brain. Decrease in norepinephrine was observed in the whole brain. Decrease in serotonin and increase in 5-hydroxyindoleacetic acid, a metabolite of serotonin, was observed in the ischemic cerebral cortex. The present study has revealed that there appears to be no significant relationship between hydroxylase cofactor activity and monoamine levels in the ischemk brain. Thus, the hydroxylase cofactor does not play a main role in regulating monoamine synthesis hi the acute phase of brain ischemia. Stroke Vol 17, No 3, 1986 TYROS1NE hydroxylase and tryptophan hydroxylase, the initial and rate-limiting enzymes in the biosynthesis of catecholamines and serotonin, require reduced pteridines as cofactors.1 -2 Tetrahydrobiopterin (BH4) is thought to be the natural cofactor.3 It has been suggested that concentration of BH4 in tissues may play a regulatory role in determining the rate of hydroxylase activity.4 ' 5 Lack of BH4 leads to a severe mental and neurological retardation or malignant hyperphenylalaninemia, 6 and defective BH4 metabolism has been suggested in Parkinson's disease, 7 senile dementia 8 and dystonia. 9 Although BH4 plays such important roles in the brain, little is known about the effect of ischemia on BH4.It has been suggested that various changes occur on monoamine neurotransmitters in the ischemic brain, which might be responsible for the brain dysfunction. There are, however, many discrepancies among findings presented by previous workers because they used experimental animals of different species or various ischemic periods, or because the distribution of ischemia was not reliably reproducible. At present, however, the rat model of four-vessel occlusion, which has recently been developed by Pulsinelli et al, 10 yields a bilateral forebrain ischemia with a relatively high reproducibility. During four-vessel occlusion, blood flow was severely reduced, to less than 3% of control values, in neocortex, striatum and hippocampus, and blood flow to the brainstem was reduced to 26%."In the present study, we have measured hydroxylase cofactor activity and concentrations of dopamine (DA), norepinephrine (NE), serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the brains of rats subjected to four-vessel occlusion, in order to evaluate the effect of ischemia on monoamine neurotransmitters and hydroxylase cofactor, 1985; accepted September 30, 1985. and to assess the role of cofactor in ischemic changes of neurotransmitters. MethodsMale Wistar rats weighing 250-300 gm were subjected to four-vessel occlusion as described by Pul...

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“…4 BH 4 ) is a natural cofactor for tyrosine hydroxylase (1,2), a rate-limiting enzyme for biosynthesis of catecholamines such as dopamine (DA), noradrenaline and adrenaline, and also a cofactor for tryptophan hydroxylase (3), a rate-limiting enzyme for biosynthesis of 5-hydrox~tr\'ptamine \.;;-HT). Because the concentration of 6R-BH 4 in the brain (4-7) is low compared with the Michaelis constants (Km values) of tyrosine hydroxylase (8)(9)(10)(11)(12)(13) and tryptophan hydroxylase (9,14) for 6R-BH 4 , tissue levels of 6R-BH 4 are considered to regulate the activities in vivo of thess enzymes. Our previous findings that intracerebroventricular administration of 6R-BH4 resulted in enhanced hydroxylation of tyrosine and tryptophan in the rat brain (15) supported this possibility.…”

Section: Introductionmentioning

confidence: 99%

6R-L-erythro-5,6,7,8-Tetrahydrobiopterin and Dopamine Release

Miwa

Koshimura

1995

Pteridines

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SummaryWe previously reported that intracerebroventricular administration of 6,7,, a cofactor for aromatic amino acid hydroxylases and nitric oxide synthase, induces an increase in DOPA levels (as an index of DA biosynthesis) and in levels of DA metabolites (as an index of DA release) in the rat brain: the increase in DOPA levels was larger than that of DA metabolites, indicating that 6R-BH 4 enhances DA release. In the present study, we examined the effects of 6R-BH 4 on DA release in vivo from the striatum of male Wistar rats and its mechanism of action using brain microdialysis. When various concentrations of 6R-BJL, 6S-BJL (a diastereoisomer of 6R-BH 4 ) or 6-methyltetrahydropterin (6-MPJL) were added to the perfusion fluid of microdialysis probes, DA levels collected in dialysates increased in a concentration-dependent manner: the 6R-BJL-induced increase was far greater than the increase induced by 6S-BH4 or 6-MPJL. Biopterin had little effect on the DA levels. After i.p. injection of250 mg/kg ofa-methyl-p-tyrosine (a-MT; an inhibitor of tyrosine hydroxylase), most of the 6R-BH 4 -induced increase persisted but the increase induced by 6S-BJL or 6-MPH4 was abolished. The 6R-BH4 -induced increase in DA levels in dialysates was abolished after addition of tetrodotoxin (50 J.1M) to the perfusion fluid, but it persisted after i.p. injection of 100 mg/kg of nomifensine which completely inhibited DA reuptake. The increase in DA levels also persisted after administration of nitric oxide synthase inhibitors. The 6R-BJL-induced increase in DA levels was inhibited by co-administration of 6S-BJL or 6-MPJL. Administration of sepiapterin (an immediate precursor of 6R-BJL) increased tissue levels of reduced biopterin (mainly consisting of 6R-BJL) but not its extracellular levels monitored by brain microdialysis, indicating that it selectively increases the intracellular 6R-BJL levels. In contrast, administration of 6R-BH 4 increased both tissue levels of reduced biopterin and its extracellular levels, indicating that it increases both the intraand extra-cellular 6R-BH 4 leveles. DA levels in dialysates was elevated following administration of sepiaterin (an immediate precursor of 6R-BJL), but the elevation was abolished after pretreatment with a-MT. Furthermore, 6R-BJL increased firing rates of neurons in the dorsal motor nucleus of vagus monitored by a slice patch method. These results suggest that 6R-BJL has a DA releasing action independent of its cofactor for tyrosine hydroxylase and nitric oxide synthase, which is mediated by a specific recognition site for 6R-BH4 on DA neurons or related cells.

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Kinetic properties of tyrosine hydroxylase purified from bovine adrenal medulla and bovine caudate nucleus

Cited by 60 publications

References 24 publications

Expression of four types of human tyrosine hydroxylase in COS cells

Expression of four types of human tyrosine hydroxylase in COS cells

Effect of ischemia on hydroxylase cofactor (tetrahydrobiopterin) and monoamine neurotransmitters in rat brain.

6R-L-erythro-5,6,7,8-Tetrahydrobiopterin and Dopamine Release

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