Glycolysis

Glycolysis (from the Greek glykys, sweet, and lysis, splitting) is the enzymatic breakdown of one 6-carbon glucose molecule into two 3-carbon pyruvic acid molecules. It is a step common to both anaerobic and aerobic respiration, and it takes place in the cytoplasm of the cell. The overall process is completed through ten enzyme-catalysed steps, organised into two phases - a preparatory phase and a pay-off phase.

Preparatory phase (first five steps). Glucose is phosphorylated twice, at the cost of two ATP molecules, and converted step by step into fructose-1,6-bisphosphate. This 6-carbon sugar is then split by aldolase into two different 3-carbon (triose) sugars - glyceraldehyde-3-phosphate and dihydroxyacetone phosphate - which are isomers of one another. Dihydroxyacetone phosphate is then itself isomerised into a second molecule of glyceraldehyde-3-phosphate, so that the preparatory phase ends with two molecules of glyceraldehyde-3-phosphate and no net ATP gained yet (2 ATP have been spent).

Pay-off phase (last five steps). Each of the two glyceraldehyde-3-phosphate molecules is oxidised and phosphorylated - using inorganic phosphate, not ATP - to 1,3-bisphosphoglycerate. Through a further series of reactions that release energy, both molecules of 1,3-bisphosphoglycerate are converted into two molecules of pyruvic acid, and the energy released along the way drives the substrate-level phosphorylation of 4 ADP to 4 ATP.

The full stepwise pathway, with each enzyme and cofactor as shown in the textbook's own 'Do you know?' diagram, runs: glucose (6C,1M) is converted by hexokinase (using ATP to ADP, with Mg²⁺) to glucose-6-phosphate (6C,1M); phosphohexose isomerase converts this to fructose-6-phosphate (6C,1M); phosphofructokinase (using ATP to ADP, with Mg²⁺) converts this to fructose-1,6-diphosphate (6C,1M); aldolase splits this into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate (3C,1M each), which triose phosphate isomerase interconverts into two molecules of glyceraldehyde-3-phosphate (3C,2M); triose phosphate dehydrogenase (using 2NAD⁺ → 2NADH+H⁺, with Zn²⁺) converts these to 1,3-bisphosphoglycerate (3C,2M); phosphoglycerate kinase (using 2ADP → 2ATP, with Mg²⁺) converts this to 3-phosphoglycerate (3C,2M); phosphoglycerate mutase converts this to 2-phosphoglycerate (3C,2M); enolase (releasing 2H₂O, with Mg²⁺) converts this to 2-phosphoenolpyruvate (3C,2M); and pyruvate kinase (using 2ADP → 2ATP, with Mg²⁺, in a final non-enzymatic step) converts this to pyruvic acid (3C,2M).

Overall reaction of glycolysis:

Glucose + 2ATP + 2Pᵢ + 4ADP + 2NAD⁺ → 2 Pyruvate + 2ADP + 4ATP + 2NADH+H⁺ + 2H₂O

Net, glycolysis therefore yields 2 ATP (4 produced minus 2 consumed) and 2 NADH+H⁺ per glucose molecule, in addition to the two pyruvate molecules themselves.

Regulation. Glycolysis is under tight control. Its rate depends on the cell's ATP requirement, and is set by a complex interplay between ATP consumption, regeneration of NADH₂, and the regulation of key glycolytic enzymes such as hexokinase, phosphofructokinase-1 (PFK-1) and pyruvate kinase. Hormones such as glucagon, epinephrine and insulin also regulate the pathway's rate. …