Complicating factors in the application of the 'average method' for determining the contribution of gluconeogenesis

摘要

TO THE EDITOR: We are writing with regard to the study by Chacko et al. (3). Although we commend Dr. Haymond's team for addressing a difficult and important problem, the concept of using an "average" label incorporation requires additional consideration. We are concerned about whether the hydrogen/ deuterium bound to carbon 1, 3, 4, 5, and 6 of glucose exchange equally during gluconeogenesis, as required for the validity of this method (3), especially since nongluconeogenic exchange reactions and/or kinetic isotope effects influence these sites differently (4, 9-11). Although Chacko et al. found agreement between the hexamethylenetetramine (HMT) method and their "average method" (implying equal exchange in the various positions), the limited range of physiological conditions is understated (3). For example, Katz and coworkers (10) demonstrated that the positional labeling of newly made glucose is affected in a substrate-specific manner.