NONCOORDINATED RESPONSES OF BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE SUBUNIT GENES TO DIETARY-PROTEIN

The response of the murine genes encoding the subunits of branched-chain alpha-ketoacid dehydrogenase complex (BCKAD) to changes in dietary protein was determined. Steady-state RNA levels for two of the subunits, E1beta and E2, decreased by two- to four-fold in the livers of mice fed 0% protein isocaloric diets compared to the levels observed in mice fed standard (23%) or high (50%) protein isocaloric diets. In contrast, the levels of RNA encoding the E1alpha subunit did not change significantly in response to these dietary protein changes. The hepatic decreases in E1beta and E2 RNA associated with 0% protein isocaloric diets were reversible, with prompt return to baseline levels following 48 hours of 50% protein isocaloric diets ad libitum. In kidney, no significant changes in the RNAs encoding any of the three BCKAD subunits were observed in response to changes in dietary protein. Studies of RNA variations associated with growth and development in several murine tissues, including liver and kidney, demonstrated coordinated changes between all subunits. Similar coordinated changes were observed during 3T3-L1 adipocyte differentiation. These studies suggest that the responses of the BCKAD subunit genes to alterations in dietary protein are noncoordinated and tissue-specific, in contrast to the coordinated changes observed during growth and/or differentiation. The differences in BCKAD subunit RNA levels observed under varying nutritional and developmental conditions suggest that multiple regulatory mechanisms modulate BCKAD subunit expression.