NAD-dependent methylenetetrahydrofolate dehydrogenase is expressed by immortal cells.

An enzyme activity not detected in normal cells is expressed in embryonic, undifferentiated, or transformed cells. Twenty-one established mammalian cell lines, both tumorigenic and nontumorigenic, were found to have an NAD-dependent methylenetetrahydrofolate dehydrogenase (Scrimgeour, K.G., and Huennekens, F.M. (1960) Biochem. Biophys. Res. Commun. 2, 230-233) in addition to the well-characterized NADP-specific activity. The NAD-dehydrogenase in cell extracts can be separated from the NADP activity by column chromatography. Normal adult tissues including brain, heart, skeletal muscle, liver, and kidney contain the NADP but not the NAD activity. Only normal tissues which contain differentiating cells such as bone marrow, thymus, spleen, and embryonic liver contain the NAD activity. The distribution of the NAD enzyme suggests that it could be useful as an oncodevelopmental marker. Its physiological role is unknown, but it is proposed that it promotes purine synthesis and perhaps contributes to the methionine dependence and rapid growth observed for many established lines.