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PMID: 6107909 Published · ppublish English Journal Article

Activation of brain tryptophan hydroxylase by ATP-MG2+: dependence on calmodulin.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 77 ·No. 8 ·1980-08-00 ·Pages 4688-91

Kuhn DM, O'Callaghan JP, Juskevich J, Lovenberg W

Abstract

Tryptophan hydroxylase [tryptophan 5-monooxygenase, L-tryptophan,tetrahydropterin:oxygen oxidoreductase (5-hydroxylating), EC 1.14.16.4] is activated by phosphorylating conditions (ATP-Mg2+) in a calcium-dependent, cyclic AMP-independent manner. Addition to the phosphorylation reaction of certain antipsychotic drugs that bind to calmodulin, the heat-stable calcium-binding protein, prevents the activation of tryptophan hydroxylase by ATP-Mg2+ in a concentration-dependent fashion. External addition of purified calmodulin protects the enzyme from the drug-induced effects. Calmodulin-free tryptophan hydroxylase prepared by affinity chromatography on fluphenazine-Sepharose is not activated by ATP-Mg2+ whereas addition of calmodulin to calmodulin-free enzyme restores the responsiveness of the hydroxylase to ATP-MG2+ only in the presence of Ca2+. These results indicate that the activation of tryptophan hydroxylase by phosphorylating conditions is dependent on both calcium and calmodulin.

MeSH Terms
Adenosine Triphosphate/pharmacology Animals Antipsychotic Agents/pharmacology Brain/enzymology Calcium-Binding Proteins/pharmacology Calmodulin/antagonists & inhibitors,pharmacology Enzyme Activation/drug effects Magnesium/pharmacology Male Phosphorylation Rats Tryptophan Hydroxylase/metabolism
Chemicals
Antipsychotic Agents Calcium-Binding Proteins Calmodulin Adenosine Triphosphate Tryptophan Hydroxylase Magnesium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kuhn D M
O'Callaghan J P
Juskevich J
Lovenberg W
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23 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.77.8.4688
Published
1980-08-00
Pages
4688-91
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC349911
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.77.8.4688 PMC Full Text View journal details
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