Betaine homocysteine S-methyltransferase (BHMT) and betaine homocysteine S-methyltransferase 2 (BHMT-2) are mammalian cytosolic metalloenzymes. They both participate in the metabolism of homocysteine (Hcy), specifically Hcy remethylation, mainly in liver and kidney cells. BHMT catalyzes the transfer of a methyl group from betaine to L-Hcy, yielding L-methionine and dimethylglycine (DMG). BHMT-2 catalyzes the transfer of a methyl group from S-methylmethionine (SMM) to L-Hcy as well, yielding two molecules of L-methionine. Disorders in Hcy metabolism could lead to the so called hyper- homocysteinemia and homocystinuria, which can be connected with several pathological conditions. BHMT is already relatively well characterized enzyme. Its crystal structure and reaction mechanism have been described and a series of BHMT inhibitors have been prepared. The specific inhibitors enabled further in vivo studies and, recently, Bhmt-/- mice model has been successfully developed. In contrast, the research of BHMT-2 is still at the beginning and physiological functions of the enzyme are unknown so far. The reason is that BHMT-2 is a highly unstable enzyme and also there is a lack of selective BHMT-2 inhibitors. BHMT and BHMT-2 are very similar enzymes which have 73% amino acid identity. This thesis provides new...