Glycolysis is the sequence of reactions that converts glucose into pyruvate with the concomitant production of a relatively small amount of ATP.
Glycolysis can be carried out anerobically (in the absence of oxygen) and is thus an especially important pathway for organisms that can ferment sugars. For example, glycolysis is the pathway utilized by yeast to produce the alcohol found in beer. Glycolysis also serves as a source of raw materials for the synthesis of other compounds. For example, 3 phosphoglycerate can be converted into serine, while pyruvate can be aerobically degraded by the Krebs or TCA cycle to produce much larger amounts of ATP
Glycolysis is the anaerobic catabolism of glucose. It occurs in virtually all cells. In eukaryotes, it occurs in the cytosol. The free energy stored in 2 molecules of pyruvic acid is somewhat less than that in the original glucose molecule. Some of this difference is captured in 2 molecules of ATP.
C6H12O6 + 2NAD+ → 2C3H4O3 + 2NADH + 2H+
- 2 ATPs are required to prepare glucose for catabolism (to activate it).
- ATP adds a phosphate group to a glucose terminal carbon (generating fructose 6-phosphate and ADP).
- Another ATP adds a phosphate gorup to the other terminal carbon (generating fructose 1,6-diphosphate and another ADP).
- At this point, we have fructose 1,6-diphosphate (glucose with a phosphate on each end) and 2 ADP.
- Next, the glucose splits in half to generate 2 molecules of glyceraldehyde 3-phosphate, which is just 3 carbons with a phosphate at the end.
- NAD+ reduces to NADH while at same time a phosphate gets added to the G3P.
- The ADP generated are each detach a phosphate to regenerate ATP.
- Another 2 ADP are converted to ATP.
The following reactions have occurred:
- Phosphoryl Transfer: a phosphoryl group is transferred from ATP to a glycolytic intermediate, or from the intermediate to ADP, by a kinase.
- Phosphoryl Shift: a phosphoryl group is shifted from one oxygen atom to another within a molecule by a mutase.
- Isomerization: the conversion of a ketose to an aldose, or vice versa, by an isomerase.
- Dehydration: the removal of water by a dehydratase.
- Aldol Cleavage: the splitting of a carbon-carbon bond in a reversal of an aldol condensation by an aldolase.
Glycolysis Part One: Preparatory Phase
Hexokinases phosphorylate a glucose molecule, forming glucose 6-phosphate.
This consumes ATP, but lowers the intracellular glucose concentration. A low intracellular glucose concentration promotes continuous transport of glucose into the cell via plasma membrane transporters. Also, since there are no cellular transporters for glucose 6-phosphate, this reaction prevents glucose from leaking out. Cofactors: Mg2+
Glucose phosphate isomerase rearranges glucose 6-phosphate (F6P) into fructose 6-phosphate.
At this point, fructose can also enter the glycolytic pathway. This change in structure is an isomerization, where G6P has been converted to F6P. This reaction requires phosphohexose isomerase, a catalytic enzyme. This reaction is freely reversible, but is driven forward by a low concentration of F6P since F6P is constantly consumed during the next step of glycolysis. Accordingly, by Le Chatelier's principle, this same reaction will favor G6P under conditions of abundant F6P.
Phosphofructokinase (PFK-1) forms &Beta-D-fructose 1,6-bisphosphate by transferring a phosphate from ATP onto &Beta-D-fructose 6-phosphate (F6P).
This ATP-dependent reaction is justified because the glycolytic process is now irreversible, and fructose 1,6-bisphosphate is much less stable than fructose 6-phosphate. Since glycolysis is now irreversible up to this point, this reaction is a key regulatory point. Cofactors: Mg2+
By destabilizing &Beta-D-fructose 1,6-bisphosphate by adding a phosphate group to it, the heoxse ring can be split by aldolase into two triose sugars.
These two triose sugars are dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.
Triosephosphate isomerase rapidly interconverts dihydroxyacetone phosphate with glyceraldehyde 3-phosphate (GADP). GADP proceeds further into glycolysis.
The activity of triosephosphate isomerase is advantageous because it directs dihydroxyacetone phosphate down the same pathway as GADP, making glycolysis more efficient.
Glycolysis Part Two: Pay-Off Phase
The two triose sugars are dehydrogenated and inorganic phosphate is added to them.
This forms two molecules of 1,3-bisphosphoglycerate. The hydrogen is used to reduce two molecules of NAD, a hydrogen carrier, to give NADH and H+.
Phosphoglycerate kinase enzymatically transfers a phosphate from 1,3-bisphosphoglycerate to ADP.
ATP and 3-phosphoglycerate is formed. At this point, glycolysis has broken even: 2 molecules of ATP have been synthesized and consumed. This step does not occur under conditions of minimal ADP (excess ATP) since, as one of two substrate-level phosphorylations, it requires ADP. Since ATP decays rapidly when not metabolized, this is an important regulatory point in the glycolytic pathway. Cofactors: Mg2+
Phosphoglycerate mutase converts 3-phosphoglycerate to 2-phosphoglycerate.
Since phosphoglycerate mutase is a mutase and not an isomerase, the oxidation state of the carbons remains the same.
Enolase forms phosphoenolpyruvate from 2-phosphoglycerate.
Cofactors: 2 Mg2+ (one ion to coordinate with the carboxylate group of the substrate, and one ion to catalyze the dehydration)
Pyruvate kinase forms one molecule of pyruvate and one molecule of ATP by a second (and final) substrate-level phosphorylation.
Much like the action of phosphoglycerate kinase, this is a regulatory step.