Betaine-Homocysteine S-Methyltransferase

BHMT is an enzyme of choline and sulfur amino acid metabolism that supports the biosynthesis of Met (Figure 7.1) and S-adenosylmethionine, the latter of which is required for over 200 different methylation reactions in humans (Petrossian and Clarke, 2011). There have been numerous studies that have investigated the tissue and subcellular distribution of BHMT in mammalian species. Although relatively low levels of activity, protein or mRNA can be detected in many tissues, the majority of BHMT in most mammals resides in the liver, with secondary sites of significant expression limited to kidney and pancreas. In liver, BHMT represents 0.5–2% of the soluble protein. In human and pig liver, the expression of BHMT is evenly distributed throughout the lobule, but in rat liver there is a gradient of expression with periportal hepatocytes expressing more that centrilobular hepatocytes. In pigs, guinea pigs and primates, the enzyme is abundantly expressed in kidney where it is has been specifically localized to the proximal tubules of the cortex. A third location where high expression has been observed is in the pancreas of sheep and guinea pig. In terms of subcellular localization, BHMT expression has so far only been localized to the cytoplasm, and a portion of which has been found to be specifically associated with microtubules.