Abstract
S-Adenosyl- l-methionine (SAM) is the biological methyl-group donor for the enzymatic methylation of numerous substrates including proteins. SAM has been reported to activate smooth muscle derived ryanodine receptor calcium release channels. Therefore, we examined the effects of SAM on the cardiac isoform of the ryanodine receptor (RyR2). SAM increased cardiac sarcoplasmic reticulum [ 3H]ryanodine binding in a concentration-dependent manner by increasing the affinity of RyR2 for ryanodine. Activation occurred at physiologically relevant concentrations. SAM, which contains an adenosine moiety, enhanced ryanodine binding in the absence but not in the presence of an ATP analogue. S-Adenosyl- l-homocysteine (SAH) is the product of the loss of the methyl-group from SAM and inhibits methylation reactions. SAH did not activate RyR2 but did inhibit SAM-induced RyR2 activation. SAH did not alter adenine nucleotide activation of RyR2. These data suggest SAM activates RyR2 via a site that interacts with, but is distinct from, the adenine nucleotide binding site.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: Biochemical and Biophysical Research Communications
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.