INDIRECT, DIRECT AND PSEUDODIRECT PATHWAYS OF LIVER-GLYCOGEN SYNTHESIS

Differences between the definitions of the contribution of the so-called direct (from glucose) and indirect (from gluconeogenesis) pathways of liver glycogen synthesis are noted. Our definition of the direct pathway involves determination of the net flux between glucose and glucose-6P, and unless glucokinase flux exceeds glucose-6-phosphatase flux, we consider the direct pathway contribution to be zero, since there is no net glucose uptake in the system for conversion to glycogen (or any product). The Landau-McGarry definition of the direct pathway involves only conversion of label from glucose to glycogen, irrespective of the net direction of flux. This incorporation of label should more properly be called a 'pseudodirect' pathway, based on the analogy to the Landau terminology of 'pseudoketogenesis', describing the conversion of label from palmitate to acetoacetate in muscle, at the same time that the net flux of acetoacetate may be in the opposite direction.