Metabolic cycle, cell cycle, and the finishing kick to Start

Yeast, like my children, are at their most vibrant in high concentrations of sugar. The budding yeast Saccharomyces cerevisiae extracts just 2 moles of ATP per mole of glucose via fermentation (that is, glycolysis to pyruvate, then reduction of the pyruvate to ethanol), but it grows rapidly with a doubling time of about one and a half hours. In low concentrations of glucose (or in non-fermentable carbon sources) yeast grow via oxidative respiration, extracting more than 30 moles of ATP per mole of glucose - but now their doubling time increases to 3 hours or longer.Yeast growing oxidatively in limited glucose use this glucose in three major ways. First, of course, they use it as an energy source; glucose flows through glycolysis to generate ATP, NADH and pyruvate, and the pyruvate flows through the tricarboxylic acid (TCA) cycle and oxidative phosphorylation to generate even more ATP. Second, they use glucose as a raw material for building the cell wall. Third, another large portion of the glucose is stored, some in the polysaccharide glycogen and some in the disaccharide trehalose. So, even though these respiring cells are in some sense starved for glucose (as they could grow faster if more glucose were available), they nevertheless store a fair portion of the glucose. About 16% of the dry weight of a respiring cell is stored carbohydrate (that is, glycogen plus trehalose), whereas a cell growing via fermentation on abundant glucose has virtually no stored carbohydrate [1,2].The fate of this stored carbohydrate is remarkable. The story is old [3-5] but complex. And recent studies [6,7] showing the oscillation of many genes as a function of the metabolic cycle have added another level of complexity, as discussed later. In the long G1 phase of a slowly growing, glucose-limited cell, cells oxidize glucose to grow by respiration, but they also store glucose as glycogen and trehalose. But in late G1, some event, possibly a spike in the level of cyclic AMP [8], changes a