Our research is focused upon vitamin B12 and folate-dependent homocysteine (or 'single carbon' ) metabolism.  Single carbon metabolism is vital for maintaining important cellular methylation reactions.  There is increasing evidence that these metabolic pathways are altered in individuals with cognitive impairment (for review see Garcia and Zanibbi CMAJ 2004 )

In the methionine cycle B12 dependent methionine synthase (MS) catalyzes the transfer of a methyl group from methyl-tetrahydrofolate (methyl-THF) to homocysteine, producing THF and methionine 

Activation of methionine by ATP generates S-adenosylmethionine (SAM), the universal methyl-group donor.  Methylation of an acceptor by SAM yields S-adenosylhomocysteine (SAH).  The regeneration of homocysteine by SAH hydrolase completes this cycle

In the folate cycle free THF accepts single carbon units from serine to form methylene-THF and glycine.  Methyl-THF is formed by the reduction of methylene-THF by methylene tetrahydrofolate reductase (MTHFR)

In the transsulfuration pathway cystathionine ß-synthase (CBS) catalyzes the synthesis of cystathionine from homocysteine.  The pathway continues with the synthesis of cysteine by cystathionase.  Cysteine is a rate-limiting precursor for glutathione synthesis . SAM is an inhibitor of MTHFR, but activates CBS.  This forms the basis of the SAM “switch” mechanism