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Naveen.K.

L
Natural
science

Glycolysis - derived from the Greek words (glycose -sweet


or sugar; lysis-dissolution)

Universal pathway in the living cells

Often referred to as Embden-Meyerhof pathway (E.M,


pathway) in honor of the 2 biochemists who made a major
contribution to the knowledge of glycolysis

Defined as the sequence of reactions converting glucose (or


glycogen) to pyruvate or lactate, with the production of ATP.

Glycolysis takes place in all cells of the body - enzymes of


this pathway are present in the cytosol

Aerobic or anaerobic

Anaerobic lactate is the end product

Aerobic - pyruvate is formed - further oxidized to CO2 and


H2O.

Glycolysis is a major pathway for ATP synthesis in tissues


lacking mitochondria like cornea, erythrocytes, lens etc

very essential for brain which is dependent on glucose for


energy

Glycolysis( anaerobic) may be summarized by the net


reaction
Glucose + 2ADP + 2Pi 2 lactate + 2ATP

A central metabolic pathway with many of its intermediates


providing branch point to other pathway intermediates are
useful for the synthesis of amino acids and fat.

Reversal of glycolysis along with the alternate arrangements


at the irreversible steps, will result in the synthesis of
glucose (gluconeogenesis)

pathway can be divided into 3 distinct phases


Energy investment phase or priming stage
Splitting phase
Energy generation phase.
Energy investment phase
Glucose is phosphorylated to glucose-6phosphate by hexokinase or glucokinase (both
are isoenzymes)
an irreversible reaction
dependent on ATP and Mg2+
The enzyme hexokinase is present in almost all
the tissues catalyses phosphorylation of
various hexoses (fructose, mannose etc.)

Glucokinase present in liver, catalyses the phosphorylation


of only glucose

Due to high affinity, glucose is utilized by hexokinase even


at low concentration

Glucokinase acts only at higher levels of glucose i.e., after a


meal when blood glucose concentration is high

Glucose 6-phosphate is impermeable to the cell memb & is a


central molecule with a variety of metabolic fate glycolysis, glycogenesis, gluconeogenesis and pentose
phosphate pathway

Glucose-6 phosphate undergoes isomerization to give


fructose 6-phosphate in the presence of the enzyme
phosphohexose isomerase and Mg2+.

Fructose 6-phosphate is phosphorylated to fructose1 ,6bisphosphate, enzyme - phosphofructokinase(PFK)


Irreversible step

Splitting phase

The 6 C fructose 1,6-bisphosphate is split (hence the name


glycolysis) to two 3C compounds, glyceraldehyde 3phosphate and dihydroxyacetone phosphate (DHAP) by
enzyme aldolase (fructose 1,6-bisphosphate aldolase)

enzyme phosphotriose isomerase catalyses the reversible


interconversion of glyceraldehyde 3-PO4 and DHAP

Thus, 2 molecules of glyceraldehyde 3-PO4 are obtained


from 1 molecule of glucose

Glyceraldehyde 3-phosphate dehydrogenase converts


glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate

This step is imp - formation of NADH + H+ and a high


energy compound 1,3-bisphosphoglycerate

Enzyme phosphoglycerate kinase acts on 1,3bisphosphoglycerate resulting in the formation of 3phosphoglycerate + syn of ATP (substrate level
phosphorylation)

3-Phosphoglycerate is converted to 2-phosphoglycerate by


phosphoglycerate mutase isomerization reaction

Phosphoenol pyruvate is generated from 2phosphoglycerate enzyme enolase - enzyme


requires Mg2+ or Mn2+

enzyme pyruvate kinase catalyses the transfer


of high energy phosphate from phosphoenol
pyruvate to ADP leading to the formation of ATP
(substrate level phosphorylation)

(Pyruvate kinase requires K+ and either Mg2+


or Mn2+)

This reaction is irreversible.

Under anaerobic conditions, 2 ATP are


synthesized

Under aerobic conditions, 4 ATP mol are


synthesized out of which 2 are utilized in
phosphorylation reactions so 2 ATP
synthesized

2 mol of NAD+ reduced to 2 mol of NADH


subsequently oxidized to ATP mol

1 NADH = 3 ATP

So 6 ATP + 2 ATP = 8 ATP

As a result of glycolysis, 2 pyruvic acid mol & 8


ATP mol are produced

The fate of pyruvate produced in glycolysis depends on the


presence or absence of oxygen in the cell

Under anaerobic conditions pyruvate is reduced by NADH to


lactate - enzyme lactate dehydrogenase

The NADH utilized in this step is obtained from the reaction


catalysed by glyceraldehyde 3-phosphate dehydrogenase

The formation of lactate allows the regeneration of NAD+


which can be reused by glyceraldehyde 3-phosphate
dehydrogenase so that glycolysis proceeds even in the
absence of oxygen to supply ATP.

By oxidative decarboxylation

an irreversible reaction, catalysed by a multienzyme complex pyruvate dehydrogenase complex (PDH) found only in the
mitochondria

High activities of PDH are found in cardiac muscle and kidney


The overall reaction of PDH is

Pyruvate + NAD+ + CoA

Acetyl CoA +
PDH

CO2 +NADH + H+

Glycolysis takes place in all cells of the body.


It the sequence of reactions converting glucose (or
glycogen) to pyruvate or lactate, with the production
of ATP.
very essential for brain which is dependent on
glucose for energy

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