Trehalose-6-phosphate synthase and stabilization of yeast glycolysis.

Abstract

‘Lost in transition: Startup of glycolysis yields subpopulations of nongrowing cells…’ (‘LIT’, van Heerden et al . 2014) is a massive paper from groups in Amsterdam and Delft, which deals with broad issues in metabolism and cell heterogeneity, as addressed for the predominant metabolic pathway, glycolysis, in the context of a long studied but incompletely understood yeast mutant which is impaired in use of glucose without evident direct defects in the pathway. The primary approach is the quite original one of predicting, for the mutant, the dynamics of metabolism upon glucose addition, based on a mathematical model using the known kinetics for the enzymes of the pathway. Here we will discuss this paper and provide some additional model simulations illuminating the model. The stoichiometry of the glycolytic pathway using whole yeast cells and glucose can be near to 1 Glucose → 2 Ethanol + 2 CO2. Such a simple balance may be seen in fermentative circumstances throughout biology although lactic acid is a more common end product. The pathway, as worked out in extracts in the first decades of the 20th century turned out to involve 10 or so steps to pyruvic acid, using two ATP in the upper reactions and two inorganic phosphate (Pi) and four ADP in the lower reactions, for a net, per glucose, of two inorganic phosphate (Pi) + 2ADP → 2ATP + 2 H2O (as abbreviated in Fig. 1). In the cell extracts from yeast, however, at one time the stoichiometry appeared quite different from that in whole cells, with half of the glucose accumulating as the intermediate, fructose-1,6-P2 (Fru1,6P2) under certain conditions (Harden 1923). The discrepancy between in vivo and in vitro was explained in hindsight: ATP was not yet known and rapid flux requires its constant use. …