Conversion of tyrosine hydroxylase to stable and inactive form by the end products.
We have reported previously that tyrosine hydroxylase in the crude extract from rat striatum exists in the inactive form showing almost no activity at the physiological pH and that the inactive form is produced by the action of the end products of the enzyme, such as dopamine. The incubation of the enzyme with the end products resulted in not only the inactivation but also a remarkable stabilization of the enzyme. Catechols possessing amino groups but no negatively charged groups on the side chains (catecholamine-type catechols) were effective at a concentration as low as 10(-7) M in both the inactivation and stabilization of the enzyme. In contrast, catechols not possessing positively or negatively charged side chains (3,4-dihydroxyphenylethyleneglycol-type catechols) were ineffective at a concentration of 10(-7) M but effective at a concentration of 10(-6) M for both the inactivation and stabilization. Catechols possessing negatively charged groups (3,4-dihydroxyphenylacetic acid-type catechols) were ineffective even at a concentration of 10(-6) M. Thus, the end products of tyrosine hydroxylase appear to serve to keep the enzyme inactive and stable. The reaction mechanism of the conversion of the enzyme from the active/labile form to the inactive/stable form by dopamine was also investigated.
Okuno
S
S
Department of Biochemistry, Asahikawa Medical College, Japan.
Fujisawa
H
H
D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology; D004298:Dopamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D011494:Protein Kinases / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014020:Tissue Extracts / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
D002395:Catecholamines; D002396:Catechols; D014020:Tissue Extracts; D014446:Tyrosine 3-Monooxygenase; D011494:Protein Kinases; D004298:Dopamine