REGULATION OF PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP) GENE

Phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) is a key enzyme in the synthesis of glucose in the liver and kidney and of gly ceride-glycerol in white adipose tissue and the small intestine. The g ene for the cytosolic form of PEPCK (PEPCK-C) is acutely regulated by a variety of dietary and hormonal signals, which result in alteration of synthesis of the enzyme. Major factors that increase PEPCK-C gene e xpression include cyclic AMP, glucocorticoids, and thyroid hormone, wh ereas insulin inhibits this process. PEPCK-C is absent in fetal liver but appears at birth, concomitant with the capacity for gluconeogenesi s. Regulatory elements that control transcription of the PEPCK-C gene in liver, kidney, and adipose tissue have been delineated, and many of the transcription factors that bind to these elements have been ident ified. Transgenic mice have been especially useful in elucidating the physiological roles of specific sequence elements in the PEPCK-C gene promoter and in demonstrating the key role played at these sites by th e isoforms of CAAT/enhancer binding protein in patterning of PEPCK-C g ene expression during the perinatal period. The PEPCK-C gene provides a model for the metabolic control of gene transcription.