Glycolysis (glycose = glucose, -lysis = degradation) is the metabolic pathway that converts glucose, into pyruvate. The free energy released in this process is used to form the high-energy compounds ATP (adenosine triphosphate) and NADH (reduced nicotinamide adenine dinucleotide).
Glycolysis is a determined sequence of ten enzyme-catalyzed reactions. The intermediates provide entry points to glycolysis. For example, most monosaccharides, such as fructose and galactose, can be converted to one of these intermediates. The intermediates may also be directly useful. For example, the intermediate dihydroxyacetone phosphate (DHAP) is a source of the glycerol that combines with fatty acids to form fat.
Glycolysis occurs, with variations, in nearly all organisms, both aerobic and anaerobic. The wide occurrence of glycolysis indicates that it is one of the most ancient known metabolic pathways. Indeed, the reactions that constitute glycolysis and its parallel pathway, the pentose phosphate pathway, occur metal-catalyzed under conditions of the Archean ocean also in the absence of enzymes. Glycolysis could thus have originated from chemical constraints of the prebiotic world.
The major steps of glycolysis are outlined in the graphic on the left. There are a variety of starting points for glycolysis; although, the most usual ones start with glucose or glycogen to produce glucose-6-phosphate. The starting points for other monosaccharides, galactose and fructose, are also shown.
There are five major important facts about glycolysis which are illustrated in the graphic.
Glucose with 6 carbons is split into two molecules of 3 carbons each at Step 4. As a result, Steps 5 through 10 are carried out twice per glucose molecule. Two pyruvic acid molecules are the end product of glycolysis per mono- saccharide molecule.
ATP is required at Steps 1 and 3. The hydrolysis of ATP to ADP is coupled with these reactions to transfer phosphate to the molecules at Steps 1 and 3. These reactions evidently require energy as well. You may consider that this is a little strange if the overall objective of glycolysis is to produce energy. This energy is used in the same way that it initially takes heat to ignite the burning of paper or other fuels – you need to expand some energy to get it started.
Reactions 6 and 9 are coupled with the formation of ATP. To be exact, 2 ATP are produced at step 6 (remember that the reaction occurs twice) and 2 more ATP are produced at Step 9. The net production of “visible” ATP is: 4 ATP.
– Steps 1 and 3 = – 2ATP
– Steps 6 and 9 = + 4 ATP
– Net “visible” ATP produced = 2
Reaction 5 is an oxidation where NAD+ removes 2 hydrogens and 2 electrons to produce NADH and H+. Since this reaction occurs twice, 2 NAD+ coenzymes are used.
If the cell is operating under aerobic conditions (presence of oxygen), then NADH must be reoxidized to NAD+ by the electron transport chain. This presents a problem since glycolysis occurs in the cytoplasm while the respiratory chain is in the mitochondria which has membrane that is not permeable to NADH. This problem is solved by using glycerol phosphate as a “shuttle.” The hydrogens and electrons are transferred from NADH to glycerol phosphate which can diffuse through the membrane into the mitochondria. Inside the mitochondria, glycerol phosphate reacts with FAD coenzyme in enzyme complex 2 in the electron transport chain to make dihydroxyacetone phosphate which in turn diffuses back to the cytoplasm to complete the cycle.
As a result of the the indirect connection to the electron transport at FAD, only 2 ATP are made per NAD used in step 5. If step 5 is used twice per glucose, then a total of 4 ATP are made in this manner.
If the cell is anaerobic (absence of oxygen), the NADH product of reaction 5 is used as a reducing agent to reduce pyruvic acid to lactic acid at step 10. This results in the regeneration of NAD+ which returns for use in reaction 5.