Nutritional and hormonal regulation of genes for lipogenic enzymes.

The de novo synthesis of long-chain fatty acids, a process that occurs primarily in liver in many species, is high in animals fed on diets with a high content of carbohydrate, and low in starved animals. The activities of the ‘lipogenic’ set of hepatic enzymes follow the same pattern. Two members of this lipogenic set are cytosolic malic enzyme (EC 1.1.1.40), which furnishes most of the NADPH for fatty acid synthesis in avian species, and fatty acid synthase (EC 2.3.1.85), a multifunctional polypeptide that uses seven molecules malonyl-CoA, one molecule acetyl-CoA and fourteen molecules NADPH, to synthesize one molecule saturated c16 fatty acid. Malic enzyme and fatty acid synthase are expressed at high levels in chicks and ducklings fed on a normal mash diet and at low levels in starved birds (Goodridge, 1968, 1973; Goodridge et al. 1984). When we first began these studies many years ago, our long-term objectives were (1) to identify humoral factors responsible for communicating the state of alimentation of a whole animal to its liver and (2) to define at the molecular level each step in the intracellular signalling pathway between binding of a humoral factor to its specific hepatic receptor and altered activity of these enzymes. We undertook a series of parallel investigations on malic enzyme and fatty acid synthase. Here mainly our work with malic enzyme will be discussed.