On the Site of Action of Amethopterin

Abstract

In the liver of the intact mouse, the conversion of exogenous folic acid to compounds with citrovorum-factor activity is inhibited completely by an amount of amethopterin similar to that bound to the enzyme folic acid reductase in vitro. Because this amount of amethopterin is several thousand times smaller than the LD₅₀, the toxic effects produced by the larger doses must be mediated via some additional mechanism.