PMID- 11937497
OWN - NLM
STAT- MEDLINE
DCOM- 20020624
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 21
DP  - 2002 May 24
TI  - Effects of nitroglycerin on soluble guanylate cyclase: implications for nitrate 
      tolerance.
PG  - 18253-6
AB  - Soluble guanylate cyclase (sGC) is a heterodimeric hemoprotein that catalyzes the 
      conversion of GTP to cGMP. Upon binding NO to its heme cofactor, purified sGC was 
      activated 300-fold. sGC was only activated 67-fold by nitroglycerin (GTN) and 
      Cys; and in the absence of Cys, GTN did not activate sGC. Electronic absorption 
      spectroscopy studies showed that upon NO binding, the Soret of ferrous sGC 
      shifted from 431 to 399 nm. The data also revealed that activation of sGC by 
      GTN/Cys was not via the expected ferrous heme-NO species as indicated by the 
      absence of the 399 nm heme Soret. Furthermore, EPR studies of the reaction of 
      GTN/Cys with sGC confirmed that no ferrous heme-NO species was formed but that 
      there was heme oxidation. Potassium ferricyanide is known to oxidize ferrous sGC 
      to the ferric oxidation state. Spectroscopic and activity data for the reactions 
      of sGC with GTN alone or with K(3)Fe(CN)(6) were indistinguishable. These data 
      suggest the following: 1) GTN/Cys do not activate sGC via GTN biotransformation 
      to NO in vitro, and 2) in the absence of added thiol, GTN oxidizes sGC.
FAU - Artz, Jennifer D
AU  - Artz JD
AD  - Department of Chemistry, University of California, Berkeley, California 
      94720-1460, USA.
FAU - Schmidt, Bryan
AU  - Schmidt B
FAU - McCracken, John L
AU  - McCracken JL
FAU - Marletta, Michael A
AU  - Marletta MA
LA  - eng
GR  - GM54065/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020405
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Nitrates)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
RN  - EC 4.6.1.2 (Soluble Guanylyl Cyclase)
RN  - G59M7S0WS3 (Nitroglycerin)
SB  - IM
MH  - Enzyme Activation
MH  - Guanylate Cyclase
MH  - Nitrates/*pharmacology
MH  - Nitroglycerin/*pharmacology
MH  - Oxidation-Reduction
MH  - Receptors, Cytoplasmic and Nuclear/*metabolism
MH  - Soluble Guanylyl Cyclase
MH  - Spectrum Analysis/methods
EDAT- 2002/04/09 10:00
MHDA- 2002/06/25 10:01
CRDT- 2002/04/09 10:00
PHST- 2002/04/09 10:00 [pubmed]
PHST- 2002/06/25 10:01 [medline]
PHST- 2002/04/09 10:00 [entrez]
AID - S0021-9258(20)85091-1 [pii]
AID - 10.1074/jbc.C200170200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 May 24;277(21):18253-6. doi: 10.1074/jbc.C200170200. Epub 2002 
      Apr 5.