Regulation of malic enzyme synthesis by insulin triiodothyronine, and glucagon in liver cells in culture.

Cells isolated from the livers of 17- to 19-day-old chick embryos were maintained in a chemically defined culture medium. During 3 days in culture the activity of malic enzyme, a measure of its concentration, was stimulated 2-, 23-, or 77-fold by insulin, triiodothyronine, or insulin plus triiodothyronine, respectively. Glucagon blocked the stimulation caused by insulin plus triiodothyronine. Changes in the relative synthesis of immunologically isolated malic enzyme were similar in magnitude and direction to the changes in enzyme activity. Degradation of malic enzyme was unaffected by the three hormones. Both soluble protein and malic enzyme were degraded with a t1/2 of about 30 hours. In cells preincubated for 2 days with insulin, synthesis of malic enzyme was stimulated 4.5-fold within 3 hours after adding triiodothyronine and reached an apparent new steady state after 24 to 30 hours. If the rate of enzyme synthesis was dependent on the concentration of cytoplasmic malic enzyme messenger RNA, then this messenger RNA appeared to have a t1/2 of about 18 hours. Glucagon rapidly and specifically inhibited synthesis of malic enzyme in preinduced cells, suggesting an action at the level of translation or cytoplasmic messenger RNA processing.