The first step in the process culminating in ATP synthesis by the mitochondria is glycolysis, or the anaerobic breakdown of glucose into pyruvate. Glycolysis is a 10-step process that takes place outside of the mitochondria, in the cell cytosol, and is catalyzed by a series of enzymes.
Glucose is first phosphorylated by ATP; this reaction is catalyzed by hexokinase using Mg2+ as a cofactor, and also converts the ATP molecule into ADP. The resulting glucose 6-phosphate is then reversibly converted into fructose 6-phosphate by the enzyme phosphoglucose isomerase. Fructose 6-phosphate is phosphorylated by a second molecule of ATP, forming fructose 1,6 biphosphate and an ADP. This reaction is catalyzed by phosphofructokinase using Mg2+ as a cofactor, and is largely irreversible.
The next step in glycolysis, catalyzed by fructose biphosphate aldolase, produces two products: glyceraldehyde 3-phosphate, which continues in the glycolysis pathway, and dihydroxyacetone phosphate, which is converted to glyceraldehyde 3-phosphate by triose phosphate isomerase. There are two molecules made of these intermediates for every molecule of glucose that enters glycolysis; in fact, this marks the step where the six-carbon skeleton of the glucose molecule is cleaved, and the reactions continue to yield two molecules of product (not pictured in diagram).
Glyceraldehyde 3-phosphate is then phosphorylated on carbon 1 by glyceraldehyde phosphate dehydrogenase using Mg2+ as a cofactor, forming 1,3-biphosphoglycerate. NAD+ and Pi aid in catalyzing this reaction, and NADH and H+ atoms are thus formed. The next step in glycolysis dephosphorylates 1,3-biphosphoglycerate, forming a molecule of ATP (two total, not pictured in diagram). Phosphoglycerate kinase is the enzyme that catalyzes this process, using Mg2+ as a cofactor, and 3-phosphoglycerate is the resultant product. This 3-phosphoglycerate is reversibly converted into 2-phosphoglycerate by the enzyme phosphoglyceromutase. 2-phosphoglycerate is dehydrated by enolase, which uses Mg2+ as a cofactor, forming phosphoenolpyruvate and two molecules of water. Phosphoenolpyruvate is then dephosphorylated, forming pyruvate and ATP. This reaction is catalyzed by pyruvate kinase, using Mg2+ as a cofactor. This pyruvate is the final product of the glycolysis pathway, along with a net gain of 2 ATP.
Now, test your knowledge by answering the questions on glycolysis!
True or false: There are 5 reactions in glycolysis that use Mg2+ as a cofactor.
There are six reactions in glycolysis that use Mg2+ as a cofactor.
What enzyme catalyzes the reversible conversion of glucose 6-phosphate to fructose 6-phosphate?
Phosphoglucose isomerase catalyzes the conversion of glucose 6-phosphate to fructose 6-phosphate.
Where does glycolysis take place in the cell?