Abstract
Serine hydroxymethyltransferase (SHMT) catalyzes the reversible interconversion of serine and tetrahydrofolate (THF) to glycine and methyleneTHF. Mammals express cytoplasmic and mitochondrial isozymes that are encoded by separate genes. Mitochondrial SHMT (mSHMT) is expressed ubiquitously and functions to generate one-carbons from serine for cytoplasmic folate-mediated one-carbon metabolism. Conversely, the expression of cytoplasmic SHMT (cSHMT) is tissue-specific, found primarily in liver, kidney, skeletal muscle and small intestinal and colonic crypts. cSHMT regulates the flow of one carbon units in the folate metabolic pathway by preferentially shuttling methylene THF into dTMP synthesis over methionine synthesis. We have generated cSHMT loss-of-function mice by deleting the cSHMT gene in the germ line. The cSHMT null mice are fertile and viable but demonstrate 3 to 5-fold elevations in the hepatic SAM/SAH ratio, indicating altered homocysteine metabolism. The data confirm results from cell culture models that indicate cSHMT represses the homocysteine remethylation cycle. Thus, alterations in cSHMT expression could impact cellular methylation reactions. This mouse model confirms the role of mitochondrial one-carbon metabolism as a primary source of one-carbons for cytoplasmic folate-mediated one-carbon metabolism. (Supported by NCI CA105440)
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: 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.
