Glycolysis

Glycolysis is the very first stage of cellular respiration, and it is common to every living cell that respires, whether the pathway that follows it is aerobic or anaerobic. The name itself, from the Greek glykys (sweet) and lysis (splitting), describes exactly what the pathway does: it splits a six-carbon sugar molecule into two three-carbon molecules of pyruvic acid (pyruvate). Because this same sequence of reactions was worked out by the biochemists Gustav Embden, Otto Meyerhof and Jakub Parnas, glycolysis is also frequently referred to as the EMP pathway. Glycolysis takes place entirely in the cytoplasm (cytosol) of the cell, outside any organelle, and this is significant, because it means glycolysis can proceed even in cells, or under conditions, where mitochondria cannot function -- for instance, under anaerobic conditions.

Although glucose is the sugar most commonly used to illustrate glycolysis, the pathway is not restricted to glucose alone: any hexose sugar can serve as the starting substrate, and in a plant cell the glucose used in glycolysis is very often derived, as and when needed, from the breakdown of stored starch or from sucrose, the principal sugar transported through the plant's phloem.

The overall sequence of glycolysis can be understood as unfolding in two broad phases. In the first, energy-investing phase, the cell actually spends ATP rather than gaining it: glucose is first phosphorylated, using one molecule of ATP, to glucose-6-phosphate, which is then rearranged to fructose-6-phosphate and phosphorylated a second time, using a second molecule of ATP, to fructose-1,6-bisphosphate. This doubly phosphorylated six-carbon sugar is then split into two separate three-carbon sugar phosphates -- glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP), which can be readily interconverted, so that in effect two molecules of G3P proceed onward through the rest of the pathway for every one molecule of glucose that entered it.

In the second, energy-yielding phase, each of these two G3P molecules is oxidised (with NAD+ accepting a pair of electrons and a hydrogen to become NADH) and simultaneously phosphorylated, forming 1,3-bisphosphoglycerate; because this happens to both three-carbon fragments, this single step yields two molecules of NADH per original glucose molecule. From this point on, a short series of further rearrangements releases the phosphate groups from each three-carbon intermediate directly onto ADP, a form of energy capture called substrate-level phosphorylation, generating ATP molecules directly without involving oxygen or the electron transport system at all. By the end of the pathway, each of the two three-carbon fragments has been converted into a molecule of pyruvic acid.

Counting up the ATP used and gained across the whole sequence gives the net result of glycolysis: two ATP were spent in the energy-investing phase, but four ATP are generated by substrate-level phosphorylation in the energy-yielding phase (two ATP from each of the two three-carbon fragments), for a net gain of 2 ATP per glucose molecule, together with 2 NADH and two molecules of pyruvic acid. This is a comparatively modest energy yield -- most of the chemical energy originally present in the glucose molecule still remains locked up in the two molecules of pyruvic acid produced. …