No common energy currency: de novo lipogenesis as the road less traveled

摘要

Bees make wax (lipid) from honey (carbohydrate). Pigs fatten on a grain diet. Indeed, all organisms, from bacteria to mammals, have the enzymes of de novo lipogenesis. The physiologic function of de novo lipogenesis has therefore seemed obvious to biochemists: the de novo lipogenesis pathway links carbohydrates and fats, the 2 most important forms of chemical energy for most organisms. Because storage of energy as lipid is much more efficient than storage as carbohydrate, the presumption has been that animals use de novo lipogenesis as a metabolic safety valve for storage of carbohydrate energy present in excess of carbohydrate oxidative needs (ie, carbohydrate energy surplus). On the basis of this presumed role, inhibitors of de novo lipogenesis such as (-)hydroxycitrate, an inhibitor of ATP citrate (pro-S)-lyase have received attention as potential therapeutic agents for obesity and hyperlipidemia.