STUDIES ON NORMAL AND LEUKEMIC LEUKOCYTES. V. PYRIDINE NUCLEOTIDE TRANSHYDROGENASES*

Abstract

Leukocytes contain a TD transhydrogenase (TPNH + DPN ?=? TPN + DPNH) and a DD transhydrogenase (DPNH + DPN*[long dash][long dash]* DPN + DPNH*). The pH optima for the DD and TD transhydrogenase are 5.8 and 6.3, respectively. At their optima, the relative activity of the DD enzyme is about 3 times that of the TD enzyme. Both transhydrogenases are inhibited about 50% by p-chloromercuribenzoate at 5 x 10-4 M, and the inhibitions are reversed by the addition of thiols. Cd++ at 5 x 10-4 M inhibits the DD enzyme about 65%, but does not affect the TD enzyme; this inhibition is reversed by dithiols but not by monothiols. Thyroxine and triiodothyronine at 10-4 M inhibit the TD enzyme by about 30%, but do not affect the DD enzyme. Steroid hormones do not affect either transhydrogenase. Levels of the two transhydrogenases have been determined in 25 normal subjects and in 25 patients with leukemia. The level of the DD enzyme is 2 to 4 times higher than that of the TD enzyme in both normal and leukemic cells. The level of the TD transhydrogenase is 3 to 4 times higher than normal in acute and chronic lymphocytic leukemic cells and slightly higher than normal in chronic myelocytic cells. The level of the DD enzyme is elevated slightly above normal in the leukemic cells.