Glycolysis is the metabolic pathway that converts glucose into pyruvate, producing a small amount of ATP. It occurs in the cytosol of cells and can proceed with or without oxygen. The pathway involves 10 enzyme-catalyzed reactions that phosphorylate and then split glucose into two molecules of pyruvate, reducing NAD+ to NADH in the process. Net production is two ATP per glucose via substrate-level phosphorylation. With oxygen present, NADH can be further oxidized through the electron transport chain to produce much more ATP.

1. GLYCOLYSIS
Glycolysis is defined as the sequence of reactions converting glucose (or glycogen) to pyruvate or lactate,
with the production of ATP.
It is anaerobic phase (occurs in the absence of oxygen) of carbohydrate metabolism.
The enzymes of this pathway are present in the cytosomal fraction of the cell.
This pathway is often referred to as Embden-Meyerhof pathway (E.M pathway).
The reactions in the pathway of glycolysis are as:

2. The sequence of reactions of glycolysis can be divided into
three distinct phases:
A. Energy investment phase or priming stage.
B. Splitting phase.
C. Energy generation phase.

3. A. Energy investment phase:
1. Glucose is phosphorylated to glucose 6-phosphate by
hexokinase, Irreversible reaction, dependent on ATP and
Mg2+. The enzyme hexokinase is present in almost all the
tissues.
2. Glucose 6-phosphate undergoes isomerization to give
fructose 6-phosphate in the presence of the enzyme
phosphohexose isomerase and Mg2+.
3. Fructose 6-phosphate is phosphorylated to fructose 1,6-
bisphosphate by phosphofructokinase (PFK), it is irreversible
step.

4. B. Splitting phase:
4. The six-carbon fructose 1,6bisphosphate is split (hence the name
glycolysis) to two three-carbon compounds, glyceraldehyde 3-
phosphate and di hydroxy acetone phosphate by the enzyme aldolase
(fructose 1,6bisphosphate aldolase.
5. The enzyme phosphotriose isomerase catalyses the reversible
interconversion of glyceraldehyde 3-phosphate and dihydroxyacetone
phosphate. Thus, two molecules of glyceraldehyde 3-phosphate are
obtained from one molecule of glucose.
c. Energy generation phase.
6. Glyceraldehyde 3-phosphate dehydrogenase converts
glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate. This step is
important as it is involved in the formation of NADH + H+ and a high
energy compound 1,3-bisphosphogfycerate.
7. The enzyme phosphoglycerate kinase acts on 1,3-
bisphosphoglycerate resulting in the synthesis of ATP and formation
of 3-phosphoglycerate.
8. 3-Phosphoglycerate is converted to 2-phosphoglycerate by
phosphoglycerate mutase.

5. 9. The high energy compound phosphoenol pyruvate is
generated from 2-phosphoglycerate by the enzyme enolase.
This enzyme requires Mg2+ or Mn2+ and is inhibited by
fluoride.
10. The enzyme pyruvate kinase catalyses the transfer of high
energy phosphate from phosphoenol Pyruvate to ADP leading
to the formation of ATP.

6. GENERATION OF ATP DURING GLYCOLYSIS
1.Glyceraldehyde 3-phosphate dehydrogenase (2 NADH, ETC, oxidative phosphorylation) ---->6
ATP synthesis.
2.Phosphoglycerate kinase (substrate level phosphorylation) ----->2 ATP synthesis.
3. Pyruvate kinase (substrate level phosphorylation) ----->2ATP synthesis.
4. Two ATP are consumed in the reactions catalysed by hexokinase and phosphofructokinase---
>2 ATP utilised.
Net ATP synthesis in glycolysis in aerobic condition = 8ATP.

7. Conversion of pyruvate to Acetyl-CoA
Pyruvate is converted to acetyl CoA by oxidative decarboxylation. This is an irreversible
reaction, catalysed by a multienzyme complex, known as pyruvate dehydrogenase
complex (PDH).

8. Pyruvate + NAD+ + CoA PDH Acetyl CoA + CO2+NADH+H+
The enzyme PDH requires five cofactors (coenzymes), namely-TPP, lipoamide, FAD, coenzyme A and NAD+.
READ CAREFULLY FOR UNDERSTANDING –
Glucose is breaks down by two cycle through the following sequence.
Glucose enters into cell.
Inside cell there is cytoplasm and glucose undergo glycolysis (glucose breaks down into pyruvate and ATP in the
cytoplasm). step 1
Pyruvate is converted into Acetyl coA. step 2
ACETYL COA is transferred into mitochondria and through citric acid cycle inside mitochondria, Acetyl coA is converted
into Co2, H2O and ATP. step 3