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PMID: 6123998 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Activation of purified soluble guanylate cyclase by protoporphyrin IX.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 79 ·No. 9 ·1982-05-00 ·Pages 2870-3

Ignarro LJ, Wood KS, Wolin MS

Abstract

Soluble guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] purified from bovine lung is markedly activated (30- to 40-fold) by protoporphyrin IX (Ka, 15-25 nM) and is inhibited by hematin (Ki, 3.7 microM) when MgGTP is used as substrate. Guanylate cyclase possesses specific activities (mumol of cGMP per min/mg of protein) of 0.1-0.2 (MgGTP) and 0.3-0.5 (MnGTP) and can attain values of 2-8 (MgGTP) or 1-1.4 (MnGTP) in the presence of protoporphyrin IX. Guanylate cyclase purified in this study contains heme and is activated by nitric oxide and nitrosyl-heme to the same magnitude as that by protoporphyrin IX. With the exception of hematoporphyrin IX, close structural analogs of protoporphyrin IX, including precursors and metabolites, do not activate guanylate cyclase. The insertion of iron into protoporphyrin IX to form heme or hematin renders the metalloporphyrin an inhibitor of unactivated or activated guanylate cyclase. The data suggest that protoporphyrin IX and heme could function to modulate guanylate cyclase activity.

MeSH Terms
Animals Cattle Enzyme Activation/drug effects Guanosine Triphosphate/metabolism Guanylate Cyclase/antagonists & inhibitors,metabolism Heme/pharmacology Hemin/pharmacology Kinetics Lung/enzymology Nitric Oxide/pharmacology Porphyrins/pharmacology Protoporphyrins/pharmacology
Chemicals
Porphyrins Protoporphyrins Nitric Oxide Heme Hemin Guanosine Triphosphate protoporphyrin IX Guanylate Cyclase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ignarro L J
Wood K S
Wolin M S
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28 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.79.9.2870
Published
1982-05-00
Pages
2870-3
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC346308
Subset
IM
Grants
NIADDK NIH HHS · AM 17692 · United States
NHLBI NIH HHS · HL 06225 · United States
External Links
PubMed source DOI: 10.1073/pnas.79.9.2870 PMC Full Text View journal details
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