Glycolysis pathway

Glycolysis is an oxidative pathway of carbohydrate metabolism through which 1 molecule of glucose(6 carbon) is converted into 2 molecules of pyruvate(3 carbon), ATP and NADH. It occurs in the cytoplasm of a living cell. Under aerobic condition glucose is converted into pyruvate while under anaerobic condition Glucose is converted into 2 molecules of Lactates and ATP.

    Pyruvate molecules thus produced in the cytoplasm are carried to the mitochondria, where it enters into Linc reaction.

 Linc reaction-

     Acetyl CO-A thus produced, completely oxidized into carbon dioxide through Kreb's cycle.

 In this way, the energy stored in glucose is obtained in the form of small packets called ATP.

   

• Glycos =sugar, Lysis= breakdown
• Also called EMP(Embden, Mayerhof and Parnas) Pathway
•  The first step of the respiratory pathway
• The first step for both aerobic and anaerobic pathway
• Oxygen is not required, hence most appropriately anaerobic pathway
• Enzymes for glycolysis present in the cytoplasm
• Glucose molecule incompletely breakdown to form 2 molecules of pyruvate.
• Along with Pyruvate 2 molecules of NADH also produced.
• 4 molecules of ATP are produced during glycolysis, But 2 molecules of ATP consumed during glycolysis. 
• Hence net gain of 2 molecules of ATP during glycolysis.

Pathway

All the steps in glycolysis pathway can be divided into 3 phases-

1. Energy Investment Phase
2. Splitting Phase
3. Energy generation Phase

Steps of Glycolysis

Step- 1: Conversion of glucose to glucose-6-phosphate

 Glucose is converted into glucose-6-phosphate in the presence of enzyme Hexokinase. Magnesium(mg++), which acts as a prosthetic group, enhances the action of enzyme hexokinase. This step consumes 1 ATP molecule.

Step- 2: Conversion of glucose-6-phosphate to fructose-6-phosphate

This reaction is catalyzed in the presence of enzyme Phosphoglucose Isomerase, which transforms the six-membered ring(glucose-6-phosphate) into a five-membered ring(fructose-6-phosphate).

Step- 3: Conversion of fructose-6-phosphate to fructose-1,6-bisphosphate

Phosphofructokinase is used to catalyze the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate, where magnesium ion acts as a prosthetic group. Phosphofructokinase is also known as the pacemaker of respiration, which is activated by AMP/ADP and inactivated by excess ATP.
Here one of the high energy bonds of ATP breaks down to give ADP and the released energy is utilized to attach a phosphate group to fructose-6-phosphate.

Step- 4: Splitting off fructose-1,6-bisphosphate

Under the influence of enzyme Aldolase, fructose-1,6-bisphosphate splits into two sugars known as Dihydroxyacetone-3-phosphate and Glyceraldehyde-3-phosphate, each having 3 carbon atoms.

Step-5: Isomerisation of dihydroxyacetone-3-phosphate

Step- 6: Conversion of glyceraldehyde-3-phosphate to 1,3- bisphosphoglycerate

This reaction is catalyzed by glyceraldehyde-3-phosphate dehydrogenase, which reduces NAD+ to NADH.

Step- 7: Conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate

Phosphoglycerate kinase helps in the production of 3-phosphoglycerate from 1,3-bisphosphoglycerate. Jn this reaction, one molecule of ATP is produced via substrate level of phosphorylation(ATP is produced by direct transfer of a phosphate group from the substrate, which is phosphorylated compound, to ADP).

Step- 8: Conversion of 3-phosphoglycerate to 2-phosphoglycerate

The enzyme mutase transfers the phosphate group from the 3rd carbon to the 2nd carbon to form 2-phosphoglycerate.

Step- 9: Conversion of 2-phosphoglycerate to PEP

The enzyme enolase helps in the removal of a water molecule from 2-phosphoglycerate to form an energy-rich compound called phosphoenolpyruvate.

Step- 10: Formation of pyruvate

The enzyme PEP Kinase helps in transfer of a phosphate group from phosphoenolpyruvate to ADP to produce ATP through substrate level of phosphorylation. After removal of a phosphate group, PEP is converted into pyruvic acid.

Fate of pyruvate

Under the aerobic condition, pyruvate is reduced to lactate in the presence of enzyme lactate dehydrogenase. This lactate then enters Cori's cycle.

While under aerobic conditions, pyruvate enters the Citric acid cycle for complete oxidation.

The energy remaining in pyruvate

In the glycolysis process, only a small fraction of the total available energy of the glucose molecule is released. The two molecules of pyruvate thus formed still have a large amount of chemical potential energy of glucose. This energy can be extracted by oxidative reactions in the Citric acid cycle and oxidative phosphorylation.

Energy investment phase

   Step- 1 to step- 3 comes under Energy investment phase. Energy is utilized to carry on the reaction. In Energy investment phase of glycolysis, 2 molecules of ATP are used.

Splitting phase

 Step- 4 and step- 5 comes under splitting phase in which six carbon compound splits into two compounds, each having 3 carbon atoms.

Energy generation phase

Step- 6 to step- 10 comes under Energy generation phase. In this phase, energy is extracted in the form of small packets called ATP. In glycolysis, 4 ATP molecules are produced in the Energy generation phase.

Net ATP produced

ATP produced in Energy generation phase       = 4 ATP

ATP used in Energy investment phase             = - 2 ATP

Net ATP produced                                            = 2 ATP

Summary of glycolysis

Glucose+ 2 Inorganic Phosphate+ 2 ADP = 2 Pyruvate+ 2 ATP+ 2 NADH+ 2 Hydrogen Ion+ 2 Water

Energetics

Ne gain in glycolysis = 2 ATP

                                      2 Pyruvate

                                     2 NADH

Glycolysis is a low energy process as maximum energy of glucose is captured by molecules like Pyruvate and NADH.

Input and output of materials during glycolysis-

Total input: 1 molecule of glucose(6C), 2 ATP, 4 ADP, 2 NAD, 2 Inorganic Phosphate

Total output: 2 molecules of Pyruvic acid(2*3C), 4 ATP, 2 ADP, 2 NADH,  2 Water

ATP generation during glycolysis-

 Energy stored in NADH                                                                     =6 ATP

 The energy produced during Energy Generation phase                            =4 ATP

 Energy used during Energy Investment phase                                   = -2 ATP

 Net production of ATP in Glycolysis                                                 = 8 ATP

Significance

1. Energy is obtained in the form of small packets called ATP which is utilized in various metabolic pathways.
2. Glyceraldehyde-3-phosphate is utilized in triglycerides and phospholipids synthesis.
3. Pyruvate(end product) is used in the biosynthesis of amino acid Alanine by transamination.
4. In RBCs, Glycolysis pathway is the only source of energy.
5. The glycolytic cycle provides various biochemical compounds which are used for the synthesis of non-essential amino acid and fat.