By 
INTRODUCTION:
Glycolysis is derived from the Greek words: Glycose = sweet or sugar and Lysis = division or solution. It is a pathway in all living cells. The complete pathway was elucidated in the year 1940. This pathway is also known as the Embden-Meyerhof pathway (EMpathway) after the two biochemists who made an important contribution to the process of glycolysis.
DEFINITION:
Glycolysis is defined as the sequence of reactions that convert glucose (or glycogen) to pyruvate or lactate with the production of ATP.
PURPOSE:
Conversion of glucose to pyruvate. Pyruvate is further processed for the generation of ATP. (ATP- adenosine triphosphate, is the energy currency of the cell. The division of one mole of ATP gives energy of 7.3 calories. This energy is used by the cell for various purposes).
PLACE:
Glycolysis occurs in the cytoplasm of the cell.
OUTSTANDING FEATURES:
1. It occurs both in the presence of oxygen and in the absence of oxygen.
has. aerobic glycolysis-
It occurs in the presence of oxygen.
The final product is pyruvate.
Energy produced- 8 ATP
b. Anaerobic Glycolysis-
It occurs in the absence of oxygen.
The final product is Lactate.
Energy produced- 2 ATP.
2. It is an important pathway for ATP synthesis in tissues and cells that lack mitochondria. Examples: red blood cells, cornea, lens.
3. The brain uses almost two thirds of the total glucose in the blood. Here, glycolysis plays an important role in the production of energy for brain cells.
4. The cell uses the intermediates of glycolysis for the synthesis of amino acids and fats.
PATHWAY OF GLYCOLYSIS:
The pathway (sequence of reactions) is divided into 3 distinct phases:
Phase 1: Energy Investment Phase.
Phase 2: Division phase.
Phase 3: Power Generation Phase.
These three phases together constitute 10 reactions.
A GLOBAL PICTURE OF GLYCOLYSIS:
GLUCOSE
1 ↓ HEXOKINASE OR GLUCOKINASE
GLUCOSE 6-PHOSPHATE
2 ↓ PHOSPHOHEXOSE ISOMERASE
FRUCTOSE 6-PHOSPHATE
3 ↓ PHOSPHOFRUCTOKINASE
FRUCTOSE 1,6-BISPHOSPHATE
4 ↓ ALDOLASE↓
5 DHAP ↔ GLYCERALDEHYDE 3-PHOSPHATE
PHOSPHOTRIOSE ISOMERASE
6 ↓ GLYCERALDEHYDE 3-PHOSPHATE DEHYDROGENASE
1, 3-BISPHOSPHOGLYCERATE
7 ↓ PHOSPHOGLYCERATE KINASE
3-PHOSPHOGLYCERATE
8 ↓ PHOSPHOGLYCERATE MUTASE
2-PHOSPHOGLYCERATE
9↓ ENOLASE
Phosphoenol PIRuvate
10 ↓ PYRUVATE KINASE
PYRUVATE
DHAP (dihydroxyacetone phosphate)
Reactions 1, 2, 3, 4 constitute the energy investment phase
Reaction 5 is the split phase
Reactions 6, 7, 8, 9, 10 constitute the energy generation phase
(The names of the enzymes that catalyze the respective reactions are given in
the arrows)
REACTIONS IN DETAIL:
1. PHOSPHORYLATION: Glucose is phosphorylated to glucose 6-phosphate by hexokinase or glucokinase (both are Iso-Enzymes). This is an irreversible reaction. ATP and magnesium ions are needed for the reaction to occur.
2. ISOMERIZATION: Glucose 6-phosphate isomerized to fructose 6-phosphate in the presence of the enzyme phosphohexose isomerase and the magnesium ion.
3. PHOSPHORYLATION: Fructose 6-phosphate is phosphorylated to fructose 1,6-bisphosphate by the enzyme phosphofructokinase. This is an irreversible and regulatory step in glycolysis.
4. PART: The six-carbon fructose 1,6-bisphosphate is split into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP). Both are 3 carbon compounds. Aldolase is the enzyme involved in the reaction.
5. ISOMERIZATION: DHAP is isomerized to glyceraldehyde 3-phosphate by the enzyme phosphotriose isomerase. So now there are 2 molecules of glyceraldehyde 3-phosphate available.
6. OXIDATION: Glyceraldehyde 3-phosphate is oxidized to 1,3 bisphosphoglycerate by the enzyme glyceraldehyde 3-phosphate dehydrogenase (G-3-P dehydrogenase). Here a NADH molecule is generated from a NAD+ molecule. This NADH participates in the electron transport chain to produce ATP.
7. DEPHOSPHORYLATION: 1,3 Bisphosphoglycerate is converted to 3-phosphoglycerate by the enzyme phosphoglycerate kinase. Here a phosphate molecule is lost from the substrate. This phosphate is taken up by an ADP molecule to produce an ATP molecule. This is a SUBSTRATE LEVEL PHOSPHORYLATION. This is a rare example of a reversible kinase reaction. Magnesium ion is also required in this reaction.
8. ISOMERIZATION: 3-phosphoglycerate is converted to 2-phosphoglycerate by the enzyme phosphoglycerate mutase. This is an isomerization reaction.
9. DEHYDRATION: 2-Phosphoglycerate is converted to phosphoenol pyruvate by removal of a water molecule by the action of the enolase enzyme. Magnesium ions or manganese ions are needed for this reaction. Phosphoenol pyruvate is a high energy compound.
10. DEPHOSPHORYLATION: Phosphoenol pyruvate is converted to pyruvate by removing a phosphate (Pi) molecule which is taken up by an ADP molecule to produce an ATP molecule. This is also a SUBSTRATE LEVEL PHOSPHORYLATION. Pyruvate kinase is the enzyme involved. The enzyme needs potassium ions and magnesium ions or manganese ions. The reaction is irreversible.
ENERGETICS OF GLYCOLYSIS:
1. 1 NADH molecule participates in ETC (Electron Transport Chain) to release 3 ATP. There are 2 NADH produced from 2 glyceraldehyde 3-phosphate molecules that release 6 ATP.
2. 1 molecule of ATP is produced by substrate level phosphorylation in reaction 7. A total of 2 ATP are produced since there are 2 molecules of glyceraldehyde 3-phosphate.
3. In reaction 10, there is again substrate level phosphorylation from phosphoenol pyruvate. Since there are 2 molecules of phosphoenol pyruvate produced from 2 molecules of glyceraldehyde 3-phosphate, 2 ATP are released.
4.In energy investment phase 2, ATP is used. 1 ATP in reaction 1 and 1 ATP in reaction 3.
So, the net synthesis of ATP in glycolysis is 8 ATP
(2NADH = 6 ATP
Reaction 7 = 2 ATP
Reaction 10 = 2ATP
Total = 10 ATP
ATP used = 2 ATP (in energy investment phase)
Net Production= 10-2=8 ATP)
NOTE:
ANAEROBIC GLYCOLYSIS:
Here pyruvate is converted to lactate by lactate dehydrogenase. Here a NADH is converted to NAD. That means that the NADH produced in reaction 6 is not used for the production of ATP. Therefore, only 2 ATP are produced here.
(2 NADH = 0 ATP
Reaction 7=2 ATP
Reaction 10=2ATP
ATP Used = 2 ATP (in energy investment phase)
Net Production=4-2=2ATP)
FATE OF PYRUVATE: The pyruvate produced as the end product of glycolysis undergoes oxidative decarboxylation and thus forms acetyl Co-A which is used in the citric acid cycle to generate ATP.
IGLYCOLYSIS INHIBITORS:
1. Iodoacetate and arsenate inhibit the enzyme glyceraldehyde 3-phosphate dehydrogenase from reaction 6.
2. Fluoride inhibits enolase from reaction 9.
DETAILS RELATED TO GLYCOLYSIS:
1. Lactic acidosis: Lactic acid buildup is seen in its excess production due to anaerobic glycolysis, example: In skeletal muscle during strenuous exercise. Lactic acidosis may also be due to its decreased elimination. In lactic acidosis, ATP production is reduced. Here the reason is the lack of oxygen supply. It can cause muscle pain during strenuous exercise. Normal concentration of lactic acid in plasma: 4-15 mg/dl.
2. Oxygen debt: It is the extra amount of oxygen needed to recover from anaerobic glycolysis.
3. Cancer and glycolysis: During cancer there is an excessive proliferation of cells. Excess cells show increased glucose uptake and therefore glycolysis. As the tumor grows in size, the tumor’s demand for oxygen increases, which the blood vessels cannot supply. Then, hypoxic conditions are established in the tumor. So, anaerobic glycolysis increases.
Later, the tumor cells become accustomed to hypoxia by the involvement of the transcription factor called Hypoxia-inducible Transcription Factor (HIF). HIF increases the synthesis of glycolytic enzymes and glucose transporters.
However, tumors cannot survive for long under these hypoxic conditions. Therefore, one method of cancer treatment is to reduce the vascularity of the tumor so that hypoxia prevails and cancers can be eliminated.
4. Shepherd Effect: The inhibition of glycolysis by oxygen (aerobic condition) is known as the Pasteur effect. It is due to the inhibition of the enzyme Phosphofructokinase of reaction 3 by the effect of the ATP produced in the presence of Oxygen via Glycolysis.
5. Crab Tree Effect: The phenomenon of inhibition of oxygen uptake by the addition of glucose to tissues that have high aerobic glycolysis. It is because when glucose is added to a tissue that it has high aerobic activity. Glycolysis More glycolysis occurs leading to the production of more ATP. Thus, the need for oxygen to produce ATP through the citric acid cycle is reduced, and therefore oxygen consumption is reduced.