GROUP 4

NITI KR. SHAH

ANUP BIK. SHAH
REVOLUTION SHERETHA
SMIRITI KHADKA
BIJAY RAJBANSHI
TAKAR ABDIGANI

GLYCOLYSIS AND
GLUCONEOGENESIS

INSTRUCTOR-RCL
Glycolysis (Embden-Meyerhof
pathway)
• Glycolysis is the breakdown of
glucose into pyruvic acid

• Does not require oxygen

• Occurs free in the cytoplasm

• Begins with D-glucose as the

substrate
 The two parts of glycolysis:

Part one(enery invesment phase):

glucose glucose 6-phosphate fructose 1,6-
ATP diphosphate
ATP

Part two(energy generating phase):

fructose 1,6-
2 pyruvic acid
diphosphate
2 NADH 2 ATP 2 ATP
 Glycolysis

• Overall net equation is:

Glucose + 2NAD + 2ADP + 2Pi 2 pyruvates +
2NADH + 2 ATP + 2 NADH + 2 H+ + 2 H2O
• Glycolysis is exergonic - produces net of
2ATPs and 2NADHs
 Glycolysis
• Coenzyme NAD+ is a biological oxidizing
agent that converts C-H bonds to C-O
bonds. In the process, NAD+ is reduced to
NADH + H+.
• The phosphorylation of ADP requires energy
and forms ATP, a high-energy nucleoside
triphosphate.
• The hydrolysis of ATP releases energy and
forms ADP
 Steps in glycolysis
• Step 1
• Substrate glucose is phosphorylated by
hexokinase
• Product is glucose-6-phosphate
– Source of the phosphoryl group is ATP
– Expenditure of ATP early in the pathway works as
energy “debt” necessary to get the pathway started
Step 1
Step 2
• Product of step 1 is rearranged to the
structural isomer fructose-6-phosphate by
enzyme phosphoglucose isomerase
- Converts and aldose to a ketose
 Step 3
• Substrate fructose-6-phosphate is
phosphorylated by phosphofructokinase
• Product is fructose-1,6-bisphosphate
– Source of the phosphoryl group is ATP
•
 Step 4
• Product of step 3 is split into two 3-carbon
intermediates by the enzyme aldolase
forming:
– Glyceraldehyde-3-phosphate (substrate of next
reaction)
– Dihydroxyacetone phosphate
 Step 5
• Dihydroxyacetone phosphate is rearranged
into a second glyceraldehyde-3-phosphate by
the enzyme triose phosphate isomerase
– Glyceraldehyde-3-phosphate is the only substrate
for the next reaction
 Step 6
• Substrate glyceraldehyde-3-phosphate is
oxidized to a carboxylic acid by glyceraldehyde-
3-phosphate dehydrogenase
– Reduces NAD+ to NADH
• Product is 1,3-Bisphosphoglycerate
– New phosphate group attached with a “high-energy”
bond
Step 7
• Harvest energy in the form of ATP
• 1,3-Bisphosphoglycerate high energy
phosphate group is transferred to ADP by
phosphoglycerate kinase:
– 3-Phosphoglycerate
– ATP
• This is the first substrate level phosphorylation
of glycolysis
 Step 8
• 3-Phosphoglycerate is isomerized into 2-
phosphoglycerate by the enzyme
phosphoglycerate mutase
– Moves the phosphate group from carbon-3 to
carbon-2
Step 9
• The enzyme enolase catalyzes dehydration of
2-phospholgycerate
– Phosphoenolpyruvate
• Energy rich – highest energy phosphorylated
compound in metabolism
 Step 10
• Final substrate-level dehydration in the
pathway
• Phosphoenolpyruvate serves as donor of the
phosphoryl group transferred to ADP by
pyruvate kinase making ATP and releasing
water
– Pyruvate is the final product of glycolysis
Summary of glycolysis
Net result of glycolysis
• The final products are:
– Two pyruvic acid molecules
– Two NADH + H+ molecules (reduced
NAD+)
– A net gain of two ATP molecules
 Glycolysis and other hexoses

• Fructose is obtained by the hydrolysis of the

disaccharide sucrose, found in sugar beets
and sugarcane

• Galactose is obtained by the hydrolysis of the

dissacharide lactose in milk

• Mannose is obtained from polysaccharides in

fruits such as cranberries and currants
 Fate of pyruvate
Acetyl CoA, CH₃COSCoA, is formed under
aerobic conditions

Lactate, CH₃CH(OH)CO2⁻, is formed under

anaerobic conditions.

Ethanol CH₃CH2OH, is formed in fermentation

 Gluconeogenesis: The
Synthesis of Glucose
• Gluconeogenesis makes glucose
from noncarbohydrate starting
materials
– Lactate
– Glycerol
– Most amino acids (not leucine, lysine)
– Glycerol and amino acids are used only
in starvation conditions
• Process occurs primarily in the liver
 The gluconeogenic pathway converts pyruvate
into glucose.

gluconeogenesis

pyruvate → → → → → glucose

glycolysis

Gluconeogenesis is not a reversal of

glycolysis
Comparison of Glycolysis
and Gluconeogenesis
• While basically opposite processes
glycolysis and gluconeogenesis are not a
simple reversal of each other

• The three nonreversible steps of glycolysis

must be bypassed with new routes
– Pyruvate  Phosphoenolpyruvate
– Fructose-1,6-bisphosphate  Fructose-6-
phosphate
– Glucose-6-phosphate  Glucose
Comparison of Glycolysis and Gluconeogenesis
 Pyruvate  Phosphoenolpyruvate
•The two enzymes that catalyze the reactions for
bypass of the Pyruvate Kinase reaction are the
following:

•Pyruvate Carboxylase (Gluconeogenesis) catalyzes:

pyruvate + HCO3 + ATP  oxaloacetate + ADP + Pi
•PEP Carboxykinase (Gluconeogenesis) catalyzes:
oxaloacetate + GTP  PEP + GDP + CO2
Pyruvate Carboxylase PEP Carboxykinase
O O
C
O O O O
C ATP ADP + Pi C O GTP GDP C
C O CH 2 C OPO32
HCO3 C CO 2
CH 3 CH 2
O O
pyruvate oxaloacetate PEP
 Fructose-1,6-bisphosphate 
Fructose-6-phosphate
• Fructose 6-phosphate is formed from 1,6-
bisphosphate by hydrolysis of the
phosphate ester at carbon1.Fructose 1,6-
bisphosphatase catalyzes this exergonic
hydrolysis
Fructose 1,6-bisphosphate + H2O 
fructose 6-phosphate + Pi
Glucose-6-phosphate  Glucose

• Glucose is formed by the hydrolysis of

gulcose 6-phosphate in a reaction
catalyzed by gulcose 6-phosphate
Gulose 6-phosphate + H2O  gulcose + Pi
 glyceraldehyde-3-phosphate
NAD+ + Pi Glyceraldehyde-3-phosphate
NADH + H+ Dehydrogenase
1,3-bisphosphoglycerate
ADP
Summary of Phosphoglycerate Kinase
ATP
Gluconeogenesis
3-phosphoglycerate
Pathway:
Phosphoglycerate Mutase
Gluconeogenesis 2-phosphoglycerate
enzyme names in
H2O Enolase
red.
phosphoenolpyruvate
Glycolysis enzyme
CO2 + GDP
names in blue. PEP Carboxykinase
GTP
oxaloacetate
Pi + ADP
Pyruvate Carboxylase
HCO3 + ATP
pyruvate Gluconeogenesis
 glucose Gluconeogenesis
Pi
Glucose-6-phosphatase
H2O
glucose-6-phosphate
Phosphoglucose Isomerase
fructose-6-phosphate
Pi
Fructose-1,6-bisphosphatase
H2O
fructose-1,6-bisphosphate
Aldolase

glyceraldehyde-3-phosphate + dihydroxyacetone-phosphate
Triosephosphate
Isomerase
(continued)
Gluconeogenesis Regulation
• Step 3 of glycolysis:
– Catalyzed by phosphofructokinase
– Stimulated by: high AMP, ADP, Pi
– Inhibited by: high ATP
• Reverse occurs in gluconeogenesis:
– Fructose-1,6-bisphosphatase stimulated by high
ATP
– At times of excess energy (high ATP)
gluconeogenesis is favored
 Reciprocal regulation of
gluconeogenesis and glycolysis in
the liver.

The interconversion of
fructose 6-phosphate
and fructose 1,6-
bisphosphate
is stringently controlled

The interconversion of
phosphoenolpyruvate
and pyruvate also is
precisely
regulated.
 Cori Cycle
• In the Cori cycle,
– Lactate from skeletal muscle is transferred to
the liver
– Converted to pyruvate then glucose
– This glucose can be returned to the muscle
THANKS