Regulation of lactate dehydrogenase levels in the mouse.

Abstract

BERNARDO NADAL-GINARD From the Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461 The number of lactate dehydrogenase molecules per cell equivalent in normal adult mouse tissues is: heart muscle 1.13 x 10s, skeletal muscle 3.6 x 1O8, liver 3.94 x lo’, and kidney 3.91 x 107. These steady state levels of lactate dehydrogenase reflect a balance between synthesis and degradation. To study the relative role of the two processes the half-lives of lactate dehydrogenase in these four mouse tissues were determined by means of a combination of the double isotope labeling technique and enzyme purification by oxamate . aminohexyl . Sepharose 4B affinity chromatog- raphy. This technique makes possible the measurement of lactate dehydrogenase turnover in single mouse organs and allows for the comparison of isotope decay between different tissues without being affected by differences in the size of the amino acid pools. All the lactate dehydrogenase isozymes in the same tissue were found to have the same half-life. The half-lives were: heart 8.2 days, skeletal muscle 43.0 days, liver 4.3 days, and kidney 6.1 days. The rates of lactate dehydrogenase synthe- sis in these tissues were calculated to be 110, 67, 74, and 52 molecules per cell per s, respectively. From these data and from the proportion of A and B subunits in each tissue, the rates of synthesis of each subunit were calculated. From the results it is concluded that the different steady state lactate dehydrogenase levels, a phenotypic expression of the lactate dehydrogenase genes, reflect mainly the differ- ing rates of degadation since the rates of synthesis are very similar; thus the regulation of the quantitative expres- sion of the lactate dehydrogenase genes in the mouse is largely post-translational.