Tetrahydrofolate-dependent enzymes and dihydrofolic reductase have been studied in human normal and psoriatic epidermis and in epidermoid carcinomas.
The levels of these enzymes are more elevated in rapidly proliferating cells of psoriasis and cancer than in normal epidermis. Dihydrofolate reductase is present in a very low amount in normal epidermis and in psoriatic epidermis without macroscopic lesions.
Amethopterin administration induces the appearance of a clearly detectable activity of dihydrofolic reductase in the epidermis of normal patients and the elevation of enzyme levels in psoriatic epidermis and in skin cancer.
The activity increase of the enzyme could be related to an enhanced synthesis induced by the drug. This seems to be proved by concurrent administration of an inhibitor of protein synthesis which is able to prevent the increase of the enzyme activity induced by amethopterin.
Grignani F, Martelli MF, Tonato M, Finzi AF. Folate-Dependent Enzymes in Human EpidermisTetrahydrofolate-Dependent Enzymes and Relationship Between Dihydrofolic Reductase and Amethopterin. Arch Dermatol. 1967;96(5):577-585. doi:10.1001/archderm.1967.01610050099017