Partial separation and properties of tyrosine hydroxylase from the human pheochromocytoma: Effect of norepinephrine

Nagatsu, Toshiharu; Yamamoto, Tomiko; Nagatsu, Ikuko

doi:10.1016/0005-2744(70)90053-7

Cited by 23 publications

(7 citation statements)

References 7 publications

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“…Concentrations of catecholamines identical to those used by Nagatsu et al (5) were tested for inhibition of the TH from six tumors and normal human adrenal medulla. Contrary to previous reports (4,5), the enzyme from all tumors exhibited sensitivity to feedback inhibition similar to that found for either human adrenal medulla or bovine adrenal medulla. Inhibition was similar with norepinephrine, epinephrine, or dopamine.…”

Section: Resultscontrasting

confidence: 77%

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Tyrosine hydroxylase in human adrenal and pheochromocytoma: localization, kinetics, and catecholamine inhibition

Waymire¹,

Weiner²,

Schneider³

et al. 1972

J. Clin. Invest.

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Section: Resultscontrasting

confidence: 77%

“…2 a and b and Table VI (5). It thus appears that, in at least some pheochromocytomas (all six that we studied), the mechanism of elevated synthesis and secretion is not via a less sensitive end product feedback inhibition.…”

Section: Xdmph4mentioning

confidence: 73%

Tyrosine hydroxylase in human adrenal and pheochromocytoma: localization, kinetics, and catecholamine inhibition

Waymire¹,

Weiner²,

Schneider³

et al. 1972

J. Clin. Invest.

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“…Abate et al (Abate et al, 1988;Abate and Joh, 1991) demonstrated by trypsin proteolysis experiments that the N-terminus of TH regulated cofactor binding. TH is inhibited by the end product catecholamines: Without preincubation, the inhibition requires high millimolar concentrations and is competi- tive with the pterin cofactor (Nagatsu et al, 1964(Nagatsu et al, , 1970Udenfriend et al, 1965;Ikeda et al, 1966), but with preincubation, the inhibition requires low micromolar concentrations (Okuno and Fujisawa, 1991). The role of the catecholamines as feedback inhibitors is thought to be of physiological significance.…”

mentioning

confidence: 99%

Dopamine Inhibition of Human Tyrosine Hydroxylase Type 1 Is Controlled by the Specific Portion in the N‐Terminus of the Enzyme

Nakashima¹,

Mori²,

Suzuki³

et al. 1999

Journal of Neurochemistry

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Tyrosine hydroxylase (TH), which converts L-tyrosine to L-DOPA, is a rate-limiting enzyme in the biosynthesis of catecholamines; its activity is regulated by feedback inhibition by catecholamine products including dopamine. To investigate the specific portion of the N-terminus of TH that determines the efficiency of dopamine inhibition, wild-type and N-terminal 3 5 , 38-, and 44-amino acid-deleted mutants (del-35, del-38, and del-44, respectively) of human TH type l were expressed as a maltose binding protein fusion in Escherichia coli and purified as a tetrameric form by affinity and size-exclusion chromatography. The fused-form wild-type enzyme possessed almost the same specific enzymatic activity as the previously reported recombinant nonfused form. Although maximum velocities of all N-terminus-deleted forms were about one-fourth of the wild-type value, there was no difference in Michaelis constants for L-tyrosine or (6R)-(~-erythro-l',2'-dihydroxypropyl)-2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine (GRBPH,) among the four enzymes. The iron contents incorporated into the three N-terminus-deleted mutants were significantly lower than that of wild type. However, there was no substantial difference in incorporated iron contents among the three mutants. The deletion of up to no less than 38 amino acid residues in the N-terminus made the enzyme more resistant to dopamine inhibition than the wild-type or del-35 TH form. Dopamine bound to the del-38 more than to the del-35 TH form. However, when incubation with dopamine was followed by further inhibition with the cofactor GRBPH, dopamine was expelled more readily from the del-38 than from the del-35 TH form. These observations suggest that the amino acid sequence G l~~~-A r g~~-A r g~~ plays a key role in determining the competition between dopamine and GRBPH, and affects the efficiency of dopamine inhibition of the catalytic activity. Key Words: Tyrosine hydroxylase [TH; tyrosine 3-monooxygenase; L-tyrosine, tetrahydr0pterin:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.21, which catalyzes the conversion of L-DOPA from L-tyrosine (Nagatsu et al., 1964), is a rate-limiting enzyme in the biosynthesis of catecholamines (Levitt et al., 1965). The enzyme requires a reduced pterin (Nagatsu et al., 1964), and (6R)-(~-erythro-1 ,2'-dihydroxypropyl)-2-amino-4-hydroxy-5,6,7,8-tebxhydropteridine (6R-tebxhydrobiopteri~ 6RBPH4) is the natural cofactor (Kaufman, 1963;Brenneman and Kaufman, 1964;Matsuura et al., 1985). TH also requires ferrous iron (Nagatsu et al., 1964;Shiman et al., 1971). TH consists of a catalytic domain (C-domain) and a regulatory domain (R-domain) (Abate and Joh, 1991). The C-domain is located at the C-terminal two-thirds of the molecule and binds the substrates (L-tyrosine and molecular oxygen) and the cofactor (6RBPH,). In contrast, the R-domain has been assigned to the N-terminal end (Hoeldtke and Kaufman, 1977;Abate et al., 1988;Abate and Joh, 1991) and has an important role in substrate specificity and in control of the catalytic activ...

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“…Tyrosine hydroxylase was known to be inhibited by the end product catecholamines without preincubation at high mM concentrations competitively with the tetrahydropterin cofactor (Nagatsu et al, 1964(Nagatsu et al, , 1970 and with preincubation at low ,aM concentrations (Okuno and Fujisawa, 1985). On the other hand, the earlier studies assigned a regulatory role to the N-terminus of tyrosine hydroxylase molecule (Hoeldtke and Kaufman, 1977;Abate et al, 1988;Abate and Joh, 1991) and following deletion studies have further defined the localization of the regulatory domain to the N-terminus.…”

Section: Discussionmentioning

confidence: 98%

Regulation of N-terminus-deleted human tyrosine hydroxylase type 1 by end products of catecholamine biosynthetic pathway

Ota

Yoshida

Nagatsu

1996

J. Neural Transmission

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The N-terminal 52-, 70-, and 157-amino acids-deleted mutants and wild-type tyrosine hydroxylases were expressed in Escherichia coli and utilized to investigate the roles of the N-terminus in the catecholamine inhibition on enzyme activity. Their lysate's supernatants were used as enzyme samples. Three catecholamines, namely dopamine, norepinephrine, and epinephrine, affected both wild-type and mutant enzymes after preincubation in the mode of mixed inhibition, and the most marked alteration among the kinetic parameters produced by the deletion was the increase in the inhibition constants. The deletions also abolished the catecholamine-induced shift of the pH profile of the enzyme activity toward a more acidic pH optimum. All three mutants responded to catecholamines almost in the same way. These results suggest that the three catecholamine end products exert their inhibition on tyrosine hydroxylase to the same extent and that the N-terminal 52 amino acid residues contain the key sequence in mediating the inhibitory action.

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Partial separation and properties of tyrosine hydroxylase from the human pheochromocytoma: Effect of norepinephrine

Cited by 23 publications

References 7 publications

Tyrosine hydroxylase in human adrenal and pheochromocytoma: localization, kinetics, and catecholamine inhibition

Tyrosine hydroxylase in human adrenal and pheochromocytoma: localization, kinetics, and catecholamine inhibition

Dopamine Inhibition of Human Tyrosine Hydroxylase Type 1 Is Controlled by the Specific Portion in the N‐Terminus of the Enzyme

Regulation of N-terminus-deleted human tyrosine hydroxylase type 1 by end products of catecholamine biosynthetic pathway

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