The document discusses glycolysis and gluconeogenesis, detailing the breakdown of glucose into pyruvate and the synthesis of glucose from non-carbohydrate sources, respectively. It outlines the steps in glycolysis, including energy investment and generation phases, and highlights the regulatory mechanisms governing these metabolic pathways. Additionally, the document explains the Cori cycle, which involves the conversion of lactate from muscles to glucose in the liver.

1. GROUP 4
NITI KR. SHAH
ANUP BIK. SHAH
REVOLUTION SHERETHA
SMIRITI KHADKA
BIJAY RAJBANSHI
TAKAR ABDIGANI
GLYCOLYSIS AND
GLUCONEOGENESIS
INSTRUCTOR-RCL

2. 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

3. 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

4. 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

5. 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

6. 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

7. Step 1

8. 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

9. Step 3
• Substrate fructose-6-phosphate is
phosphorylated by phosphofructokinase
• Product is fructose-1,6-bisphosphate
– Source of the phosphoryl group is ATP
•

10. 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

11. 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

12. 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

13. 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

14. Step 8
• 3-Phosphoglycerate is isomerized into 2-
phosphoglycerate by the enzyme
phosphoglycerate mutase
– Moves the phosphate group from carbon-3 to
carbon-2

15. Step 9
• The enzyme enolase catalyzes dehydration of
2-phospholgycerate
– Phosphoenolpyruvate
• Energy rich – highest energy phosphorylated
compound in metabolism

16. 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

17. Summary of glycolysis

18. 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

19. 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

20. 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

21. 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

22. The gluconeogenic pathway converts pyruvate
into glucose.
gluconeogenesis
pyruvate → → → → → glucose
glycolysis
Gluconeogenesis is not a reversal of
glycolysis

23. 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

24. Comparison of Glycolysis and Gluconeogenesis

25. 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

26. 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

27. 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

28. 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

29. 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)

30. 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

31. 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.

32. 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

33. THANKS