Carbohydrate Metabolism: Glycolysis

Study Notes

Glycolysis, also known as the Embden-Meyerhof Pathway, occurs in all tissues, converting glucose into energy (ATP) and intermediates for other metabolic pathways.
End products vary by oxygen availability: aerobic glycolysis produces pyruvate, while anaerobic glycolysis converts pyruvate to lactate, yielding no net ATP.
Aerobic glycolysis generates a net of 8 ATP molecules per glucose, in contrast to 2 ATP in anaerobic glycolysis.

Glycolysis consists of ten steps and occurs in the cytoplasm.
Divided into two phases:
- First Phase: Consumes energy to phosphorylate glucose.
- Second Phase: Produces energy in the form of ATP from glucose breakdown.

Phosphorylation of Glucose:
- Glucose is transformed into glucose-6-phosphate by hexokinase (or glucokinase in the liver), trapping glucose inside the cell.
Isomerization:
- Glucose-6-phosphate is converted to fructose-6-phosphate by phosphoglucoisomerase, a reversible process.
Phosphorylation of Fructose-6-Phosphate:
- Fructose-6-phosphate is irreversibly converted to fructose-1,6-bisphosphate by phosphofructokinase-1 (PFK-1), a key regulatory step activated by AMP and fructose-2,6-bisphosphate.
Cleavage of Fructose-1,6-Bisphosphate:
- Aldolase cleaves this compound into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate.

Isomerization of Dihydroxyacetone Phosphate:
- Triosephosphate isomerase interconverts the two molecules, leading to the production of two glyceraldehyde-3-phosphate molecules for further glycolytic processing.

Oxidation of Glyceraldehyde-3-Phosphate:
- Glyceraldehyde-3-phosphate is oxidized to 1,3-bisphosphoglycerate by glyceraldehyde-3-phosphate dehydrogenase with NAD+ as a cofactor; NADH produced can be reoxidized.
ATP Formation:
- Phosphoglycerate kinase catalyzes the transfer of high-energy phosphate from 1,3-bisphosphoglycerate to ADP, forming ATP (2 ATP per glucose).
Phosphate Group Shift:
- Catalyzed by phosphoglycerate mutase, this reversible reaction moves the phosphate from carbon 3 to carbon 2.
Dehydration:
- Enolase dehydrates 2-phosphoglycerate to form phosphoenolpyruvate (PEP).
Formation of Pyruvate:
- Pyruvate kinase irreversibly converts phosphoenolpyruvate to pyruvate, generating more ATP.
- Pyruvate kinase is regulated by fructose-1,6-bisphosphate (activator) and glucagon via cyclic AMP (inhibitor).

Energy Yield:
- Glycolysis culminates in a net production of ATP, highlighting its role in energy metabolism.
Regulatory Enzymes:
- Important enzymes include hexokinase/glucokinase, phosphofructokinase-1, and pyruvate kinase, each playing critical roles in the pathway's regulation.