The lactate dehydrogenases of hemopoietic cells.

By W. H. STARKWEATHER, H. H. SPENCER AND H. K. ScriocH M AMMALIAN LACTATE DEHYDROGENASE ( LDH ) can be separated into five active fractions.’4 The production of electrophoretic extremes, LDH-1 (H4 ) and LDH-5 ( M4 ), is controlled by the action of two genes.5’#{176}The intermediate fractions ( LDH-2, LDH-3, LDH-4 ) are considered hybrid forms of LDH-1 and LDH-5.5’” Assuming that the hybrids are assembled by random association of the peptides making up the LDH-1 and LDH-5 tetramers, the concentrations of the hybrids would be determined by the activity of the two alleles controlling LDH-1 and LDH-5. 7 The isoenzyme patterns of adult human tissues are organ specific,8 but all fetal tissue patterns of man are similar to each other, and are characterized by a predominance of LDH-3.7#{176} This pattern is intermediate to those of other tissues, and if random formation of hybrids is assumed, would indicate equal activity of LDH-1 and LDH-5.7 The LDH isoenzymes differ from each other in various kinetic parameters such as substrate inhibition,’4 heat stability,” and reactions with pyridine coenzyme analogues.1 The effect of increasing substrate concentration upon the five isoenzymes suggests that the isoenzyme distribution controls pyruvate metabolism in tissues, but this hypothesis is open to more experimentation.’2 During development of embryonic organs, a shift in LDH isoenzyme patterns occurs that appears to vary in different species.1 ” This paper will discuss alterations of LDH isoenzymes in blood cells with relation to LDH as an index of cellular differentiation.