Glycolysis

Glycolysis is defined as the sequence of reactions catalysed by several enzymes, in which the glucose (6-carbon compound) is broken down into two molecules of pyruvate (3-carbon compounds) or lactate, with the production of ATP and NADH.

The term glycolysis is derived from the two words: “Glyco” = sugar and “Lysis” = breakdown.

This pathway is often referred to as Embden-Meyerhof pathway (E.M. pathway) in honour of the two biochemists who made a major contribution to the knowledge of glycolysis.

Salient features of Glycolysis:

• Glycolysis occurs in all cells of the body. The enzymes needed for this process are found in the cytoplasm (cytosol) of the cell.
• Glycolysis can happen with or without oxygen.
• Without oxygen (anaerobic condition): the final product is lactate (lactic acid).
• With oxygen (aerobic condition): the final product is pyruvate, which is further broken down into carbon dioxide (CO₂) and water (H₂O) to produce more energy.
• Glycolysis is an important source of energy (ATP) for tissues that do not have mitochondria, such as red blood cells (RBCs/erythrocytes), cornea, and lens of the eye.
• Glycolysis is very important for the brain because the brain mainly uses glucose for energy. Before glucose can release full energy, it first goes through glycolysis and is then broken down further into CO₂ and H₂O.

Location of Glycolysis:

Glycolysis takes place in the cytoplasm of all cells, both in the presence of oxygen (aerobic conditions) and in the absence of oxygen (anaerobic conditions).

• In the presence of oxygen: Glycolysis occurs in the cytoplasm, and the pyruvate formed enters the mitochondria for further breakdown (aerobic respiration).
• In the absence of oxygen: Glycolysis still occurs in the cytoplasm, but pyruvate is converted into lactic acid.

Glycolysis occurs under anaerobic conditions (absence of oxygen) in certain cells and organisms, such as:

• Red blood cells (RBCs): They do not have mitochondria, so they always depend on anaerobic glycolysis for energy.
• Skeletal muscle cells during intense exercise: When oxygen supply becomes insufficient, muscles switch to anaerobic glycolysis and produce lactic acid.
• Lens of the eye: The lens has no blood supply and no mitochondria in mature lens fibers, so it mainly gets energy through anaerobic glycolysis, producing lactic acid.
• Cornea: The cornea receives limited oxygen thus here also anaerobic glycolysis occurs.

Reactions of Glycolysis:

This process occurs in several steps. The the various steps of this pathway can be divided into three distinct phases.

A. Energy investment phase or priming stage
B. Splitting phase
C. Energy generation phase.

Description of steps occurs in Glycolysis:

Stage 1

A phosphate group from ATP is added to glucose forming glucose,6-phosphate in the cell cytoplasm by the action of enzyme hexokinase. This is called the phosphorylation of glucose.

Stage 2

Glucose-6-phosphate is isomerised into fructose,6-phosphate by the enzyme phosphohexose isomerase.

Stage 3

The other ATP molecule breaks and a phosphate group is transfered to fructose 6-phosphate which converts it into fructose 1,6-bisphosphate by the action of the enzyme phosphofructokinase.

Stage 4

The enzyme aldolase converts fructose 1,6-bisphosphate into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate, which are isomers of each other.

Stage 5

Phosphotriose isomerase converts dihydroxyacetone phosphate into glyceraldehyde 3-phosphate.

Stage 6

This step catalysed by glyceraldehyde 3-phosphate dehydrogenase, in which a phosphate is attached to the glyceraldehyde 3 phosphate to form 1,3-bisphosphoglycerate and also forms NADH + H+.

Stage 7

Phosphate is transferred from 1,3-bisphosphoglycerate to ADP to form ATP with the help of enzyme phosphoglycerokinase. Thus two molecules of phosphoglycerate were formed and 2 ATP were generated at the end of this reaction.

Stage 8

The phosphate of both the phosphoglycerate molecules is relocated from the third to the second carbon to produce two molecules of 2-phosphoglycerate by the enzyme phosphoglyceromutase.

Stage 9

The enzyme enolase removes a water molecule from 2-phosphoglycerate to form phosphoenolpyruvate.

Stage 10

A phosphate from phosphoenolpyruvate is transferred to ADP to form pyruvate and 2 ATP were generated by the action of enzyme pyruvate kinase. Two molecules of pyruvate and 2 ATP are obtained as the end products.

Pyruvate to Lactate (In absence of lack of Oxygen)

Under anaerobic conditions (lack of oxygen), pyruvate is reduced by NADH to lactate in presence of the enzyme lactate dehydrogenase.

Energetics of Glycolysis:

Energy Investment Phase, which is the first phase, 2 ATP molecules are consumed.

In Energy generation phase 4 ATP molecules are produced by substrate-level phosphorylation.

So, total Energy produced = Produced ATP (4) - Consumed ATP (2) = 2 ATP net gain per glucose molecule.

2 NADH molecules are also formed, which can later produce ATP,

in aerobic conditions approx 2.5 ATP were generated from one NADH.

thus, 2 ATP + 2 NADH ( 5 ATP) = 7 ATP per glucose molecule were produced from one glucose molecule.