glycolysis

GLYCOLYSIS
the sequence of reactions for the breakdown
of glucose to pyruvate or lactate, depending
on the conditions
also called as Embden-Meyerhof-Parnas
pathway (EMP pathway)
occurs in the cytoplasm of virtually all the
cells of the body
TWO TYPES OF GLYCOLYSIS
AEROBIC GLYCOLYSIS
occurs when oxygen is plentiful. Final product is pyruvate along
with the production of eight ATP molecules.

ANAEROBIC GLYCOLYSIS
occurs when oxygen is scarce. Final product is lactate along with
the production of two ATP molecules.
AEROBIC GLYCOLYSIS
TWO PHASES
1. The Preparatory Phase
in which ATP is consumed and is hence also known as the investment
phase
Also called glucose activation phase
Steps 1-5

2. The Pay Off Phase

in which ATP is produced
Also called energy extraction phase
Steps 6-10
PHASE ONE: THE PREPARATORY PHASE
Step 1:
UPTAKE AND PHOSPHORYLATION OF GLUCOSE

glucose + ATP glucose-6-P + ADP

 Glucose is phosphorylated to form glucose-6-phosphate or G6P
Enzyme: HEXOKINASE
Hexokinase
is a key glycolytic enzyme
is in the liver and extrahepatic tissue
requires Mg2+ for its activity.
The enzyme splits the ATP into ADP, and the P is added onto the
glucose.
The reaction is irreversible
Step 2:
ISOMERIZATION OF G6P TO F6P
 Glucose-6-phosphate is isomerised to fructose-6-phosphate or F6P
Enzyme: PHOSPHOHEXOSE ISOMERASE.
This reaction involves an aldose-ketose isomerisastion catalysed by
phosphohexose isomerase.
Step 3 :
PHOSPHORYLATION OF F6P TO F1,6BP
 Fructose-6-phosphate is further phosphorylated to fructose 1,6-
bisphosphate or F1,6BP
Enzyme: PHOSPHOFRUCTOKINASE-1.
It catalyses the transfer of a phosphate group from ATP to fructose-6-
phosphate.
The reaction is irreversible.
Phosphofructokinase-1 is the key enzyme in glycolysis which
regulates breakdown of glucose.
Step 4:
CLEAVAGE OF FRUCTOSE 1,6-BIPHOSPHATE
 The 6 carbon fructose-1,6-bisphosphate is cleaved into two 3 carbon
units:
one glyceraldehyde-3-phosphate (GAP)
molecule of dihydroxyacetone phosphate (DHAP)
Enzyme: ALDOLASE
Step 5:
INTERCONVERSION OF THE TRIOSE PHOSPHATES
 GAP is the only molecule that continues in the glycolytic pathway.
As a result, all of the DHAP molecules produced are further acted on
by TPI, which reorganizes the DHAP into GAP so it can continue in
glycolysis
Enzyme: TRIOSE-PHOSPHATE ISOMERASE or TPI
PHASE TWO: THE PAY OFF PHASE
During this phase, conversion of glyceraldehyde-3-phophate to
pyruvate and the coupled formation of ATP take place.
Because Glucose is split to yield two molecules of D-Glyceraldehyde-
3-phosphate, each step in the payoff phase occurs twice per molecule
of glucose.
Step 6:
OXIDATIVE PHOSPHORYLATION OF
GAP TO 1,3-BISPHOSPHOGLYCERATE
 The first step in the payoff phase is the oxidation of glyceraldehyde 3-
phosphate to 1,3-bisphosphoglycerate.
Glyceraldehyde-3-phosphate loses two electrons and two protons,
reducing NAD+ to NADH and producing an H+
This reaction releases energy, which is used to attach another
phosphate to the sugar, forming 1,3-bisphosphoglycerate.
Enzyme: GLYCERALDEHYDE 3-PHOSPHATE DEHYDROGENASE.
Step 7 :
CONVERSION OF 1,3-BPG TO 3-PG
 1,3-bisphosphoglycerate donates one of its phosphate groups to ADP
This makes a molecule of ATP and turns 1,3-BPG into
3-phosphoglycerate or 3-PG in the process.
Enzyme: PHOSPHOGLYCERATE KINASE
Step 8:
CONVERSION OF 3-PG TO 2-PG
 3-phosphoglycerate is isomerized to 2-phosphoglycerate by shifting
the phosphate group from the 3rd to 2nd carbon atom
Enzyme: PHOSPHOGLUCOMUTASE
Step 9:
DEHYDRATION OF 2-PG TO
PHOSPHOENOLPYRUVATE
 2-phosphoglycerate is converted to phosphoenolpyruvate or PEP
Enzyme: ENOLASE
One water molecule is removed in the process of conversion
PEP is an unstable molecule, poised to lose its phosphate group in the
final step of glycolysis.
Step 10:
CONVERSION OF PEP TO PYRUVATE
 Phosphoenol pyruvate (PEP) is dephosphorylated to pyruvate
Enzyme: PYRUVATE KINASE
First PEP is made into a transient intermediary of enol pyruvate;
which is spontaneously isomerized into keto pyruvate, the stable form
of pyruvate.
One mole of ATP is generated during this reaction.
The pyruvate kinase is a key glycolytic enzyme.
This step is irreversible.
Step Enzyme Source No. of ATP
1 Hexokinase -1
3 Phosphofructokinase -1

Glyceraldehyde-3-
6 phosphate NADH (+3) x 2 = +6
dehydrogenase

Phosphoglycerate
7 ATP (+1) x 2 = +2
kinase
10 Pyruvate kinase ATP (+1) x 2 = +2
Net Yield 8 ATPs
ANAEROBIC GLYCOLYSIS
When animal tissues cannot be supplied with sufficient oxygen to
support aerobic oxidation of the pyruvate and NADH produced in
glycolysis, NAD+ is regenerated from NADH by the reduction of
pyruvate to lactate.
Some tissues and cell types produce lactate from glucose even under
aerobic conditions.
The reduction of pyruvate is catalyzed by lactate dehydrogenase.
 No. of ATP
Step Enzyme Source
Formed/consumed

1 Hexokinase -1

3 Phosphofructokinase -1

Phosphoglycerate
7 ATP (+1) x 2 = +2
kinase
10 Pyruvate kinase ATP (+1) x 2 = +2
Net Yield 2 ATPs
Krebs cycle
 Also known as TriCarboxylic Acid (TCA) cycle or the Citric Acid Cycle
is a step wise cyclic process which is used to oxidize the pyruvate
formed during the glycolytic breakdown of glucose into CO2 and
Water H2O
It also oxidizes acetyl CoA which arises from breakdown of
carbohydrate, lipid, and protein.
The actual Krebs cycle begins when acetyl CoA enters into a reaction
to form citric Acid.
In eukaryotes, the citric acid cycle takes place in the matrix of the
mitochondria
Step 1:
FORMATION OF CITRATE
 The first reaction of the cycle is the condensation of acetyl-
CoA with oxaloacetate to form citrate
Enzyme: CITRATE SYNTHASE
Once oxaloacetate is joined with acetyl-CoA, a water molecule attacks
the acetyl leading to the release of coenzyme A from the complex
Step 2:
FORMATION OF ISOCITRATE
 The citrate is rearranged to form an isomeric form, isocitrate
Enzyme: ACONTINASE
In this reaction, a water molecule is removed from the citric acid and
then put back on in another location.
The overall effect of this conversion is that the OH group is moved
from the 3 to the 4 position on the molecule. This transformation
yields the molecule isocitrate.
Step 3:
Oxidation of Isocitrate to -Ketoglutarate
 Isocitrate is coverted to -ketoglutarate.
Enzyme: ISOCITRATE DEHYDROGENASE
byproducts of are NADH and CO2
Step 4:
Oxidation of -Ketoglutarate to Succinyl-CoA
 Alpha-ketoglutarate is oxidized, carbon dioxide is removed, and
coenzyme A is added to form the 4-carbon compound succinyl-CoA
During this oxidation, NAD+ is reduced to NADH and H+
Enzyme: ALPHA-KETOGLUTARATE DEHYDROGENASE
Step 5:
Conversion of Succinyl-CoA to Succinate
 CoA is removed from succinyl-CoA to produce succinate.
The energy released is used to make guanosine triphosphate (GTP)
from guanosine diphosphate (GDP) and Pi by substrate-level
phosphorylation.
GTP can then be used to make ATP.
Enzyme: succinyl-CoA synthase
Step 6:
Oxidation of Succinate to Fumarate
 Succinate is oxidized to fumarate.
During this oxidation, FAD is reduced to FADH2.
Enzyme: SUCCINATE DEHYDROGENASE
Step 7:
Hydration of Fumarate to Malate
 The reversible hydration of fumarate to L-malate
Enzyme: FUMARASE (FUMARATE HYDRATASE)
Step 8:
Oxidation of Malate to Oxaloacetate
 Malate is oxidized to produce oxaloacetate, the starting compound of
the citric acid cycle
Enzyme: MALATE DEHYDROGENASE
During this oxidation, NAD+ is reduced to NADH and H+.
Products
The acetyl-CoA, has been oxidized to two molecules of carbon
dioxide.
Three molecules of NAD were reduced to NADH.
One molecule of FAD was reduced to FADH2.
One molecule of GTP (the equivalent of ATP) was produced.