• Glycolysis

• Energetics

• Disorders associated with glycolysis


• At the end of this
lecture, student will be able to

– Explain reaction involved in glycolysis

– Describe energetics of glycolysis

– Discuss the disorders associated with glycolysis


• Universal pathway in the living cells

• Elucidated in 1940 by Embden-Meyerhof and referred to as
Embden- Meyerhof pathway (E.M, pathway)

• Defined as the sequence of reactions converting glucose to
pyruvate or lactate, with the production of ATP

• Chemical formula: C6H12O6

Salient features

• Takes place in all cells of the body & enzymes of this
pathway are present in the cytosol of the cell

• Occurs in the absence of oxygen (anaerobic) or in the
presence of oxygen (aerobic)

• Lactate is the end product under anaerobic condition &
in aerobic condition pyruvate, which is then oxidized to CO2 & H2O

• Major pathway for ATP synthesis in tissues lacking
mitochondria e.g. erythrocytes, cornea, lens etc.

• Very essential for brain which is dependent on glucose for

• Central metabolic pathway with many of its intermediates
providing branch point to other pathways. Thus, the intermediates are useful
for the synthesis of amino acids and fat

Reactions of
The pathway can be divided into 3 phases

1. Energy investment phase or priming stage

2. Splitting phase

3. Energy generation phase.

1. Energy investment

• Glucose is phosphorylated to G-6-P by hexokinase or

• This is an irreversible reaction, dependent on ATP and

• G-6-P is impermeable to the cell membrane, thus, G-6-P
undergoes isomerization to give F-6-P in the presence of phosphohexose
isomerase and Mg2+

• F-6-P is phosphorylated to fructose 1, 6 bisphosphate by

• This is an irreversible and a regulatory step in

2. Splitting phase

• 6 C fructose 1, 6-bisphosphates split to two 3C compounds
glyceraldehyde-3-P & di hydroxyacetone phosphate by the aldolase

• Enzyme phosphotriose isomerase catalyses the reversible
interconversion of glyceraldehyde-3-P & dihydroxyacetone phosphate. Thus, 2
molecules of glyceraldehyde- 3-phosphate are obtained from one molecule of

3. Energy generation

• Glyceraldehyde-3-phosphate dehydrogenase converts
glyceraldehyde-3- P to 1,3-bisphosphoglycerate

• This step is important as it is involved in the formation
of NADH + H+ & high energy compound 1,3-bisphosphoglycerate

• NADH passes through the ETC & 6 ATP are synthesized by
oxidative phosphorylation 

• Enzyme phosphoglycerate kinase acts on
1,3-bisphosphoglycerate resulting in the synthesis of ATP and formation of
3-phosphoglycerate. This is a good example of substrate Ievel phosphorylation
and reaction is reversible

• 3-Phosphoglycerate is converted to 2- phosphoglycerate by
phosphoglycerate mutase. This is an isomerization reaction

• High energy compound phosphoenol pyruvate is generated
from 2-phosphoglycerate by enolase, requires Mg2+ or Mn2+

• Enzyme pyruvate kinase catalyses the transfer of high energy
phosphate from phosphoenol pyruvate to ADP, leads to form of ATP and pyruvate.
This step also is a substrate level phosphorylation & reaction is

• Glycolysis under aerobic condition produce pyruvate and
under anaerobic condition produce lactate

• Conversion of pyruvate to lactate is by lactate
dehydrogenase and NADH


• Normal plasma concentration lactic acid is 4-15 mg/dl

• Elevation of lactic acid in the circulation may occur due
to its increased production or decreased utilization of lactic acid

• Mild forms are associated with strenuous exercise, shock,
respiratory diseases, cancers/low pyruvate dehydrogenase activity

• Severe forms are observed due to impairment/collapse of
circulatory system which is often encountered in MI, pulmonary embolism,
uncontrolled hemorrhage and severe shock, which may even lead to death

Production of ATP

• Under anaerobic conditions, 2 ATP are synthesized while,
under aerobic conditions, 8 or 6 ATP are synthesized-depending on the shuttle
pathway that operates.

steps in glycolysis

• Three steps catalyzed by enzymes hexokinase (or
glucokinase), phosphofructokinase and pyruvate kinase, are irreversible steps

of glycolysis

• Three enzymes namely hexokinase phosphofructokinase and
pyruvate kinase, catalysing the irreversible reactions regulate glycolysis


• Glycolysis also known as Embden-Meyerhof pathway

• Sequence of reactions converting glucose to pyruvate or
lactate, with the production of ATP is known as glycolysis

• Glucose chemical formula is C6H12O6

• Glycolysis pathway is divided into 3 phases; Energy
investment phase or priming stage, Splitting phase & Energy generation

• Elevation of lactic acid in the circulation is known as
Lactic acidosis

• 8 ATP are synthesized in glycolysis

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