Glycolysis is the breakdown of glucose into pyruvate to produce energy in the form of ATP. It occurs in the cytosol of cells. The end products of glycolysis are pyruvate, which enters the mitochondria for aerobic respiration, or lactate, produced under anaerobic conditions. Glycolysis generates 2 ATP per glucose molecule during anaerobic conditions and up to 38 ATP during aerobic respiration through subsequent pathways. Key enzymes regulate glycolysis through allosteric and covalent modification mechanisms. Deficiencies in glycolytic enzymes can cause genetic disorders like pyruvate kinase deficiency which leads to hemolytic anemia.

1. Glycolysis
Introduction to Glucose Metabolism

2. Glycolysis
Glycolysis is the breakdown of glucose to:
1- Provide energy in the form of ATP (main function)
2- Provide intermediates for other metabolic pathways.
It occurs in cytosols of all tissues
All sugars can be converted to glucose & thus can be metabolized by
glycolysis.

3. End products of glycolysis
1- In cells with mitochondria & an adequate supply of oxygen
(Aerobic glycolysis)
- Pyruvate: enters the mitochondria & is converted into acetyl CoA.
Acetyl CoA enters citric acid cycle (Krebs cycle) to yield energy
in the form of ATP
- NADH: utilizes mitochondria & oxygen to yield energy
2- In cells with no mitochondria or adequate oxygen (or Both)
(Anaerobic glycolysis)
Lactate: formed from pyruvate (by utilizing NADH)

4. Overall reactions of glycolysis

5. Glycolysis
Glucose (6C)
2 Pyruvate (3C)
2 ATP
2 ADP
4 ADP
4 ATP
2 NAD
2 NADH+ H+

6. Pyruvate
is the end product
of aerobic glycolysis
Lactate
is the end product
of anaerobic glycolysis
End products of glycolysis
NADH
is an end product
of aerobic glycolysis
AEROBIC GLYCOLYSIS
Mitochondria & Oxygen
ANAEROBIC GLYCOLYSIS
No mitochondria
No Oxygen
Or Both

7. Key enzymes in glycolysis
1- Hexokinase & Glucokinase
Glucose Glucose 6-phosphate
2- Phosphofructokinase (PFK)
Fructose 6-phosphate Fructose 1,6 bisphosphate
3- Pyruvate Kinase (PK)
Phosphoenel pyruvate Pyruvate

8. Steps catalyzed
By
key enzymes
ONE WAY REACTIONS
1
2
3
Key enzymes in glycolysis

9. Energy yield from glycolysis
1- Anaerobic glycolysis
2 molecule of ATP for each one molecule of glucose converted to 2 molecules of lactate
It is a valuable source of energy under the following conditions
1- Oxygen supply is limited as to the cells
2- Tissues with no mitochondria skeletal muscles during intensive exercise
Kidney medulla
RBCs
Leukocytes
Lens & cornea cells
Testes
2-Aerobic glycolysis
2 moles of ATP for each one mol of glucose converted to 2 moles of pyruvate
2 molecules of NADH for each molecule of glucose
2 or 3 ATPs for each NADH entering electron transport chain (ETC) in mitochondria.

10. Energy yield from glycolysis
In anaerobic glycolysis:
2 ATP for one glucose molecule
In aerobic glycolysis
Glycolysis: 2 ATP
2 NADH: 2 X 3 = 6 ATP
NADH
Pyruvate Acetyl CoA
2 Pyruvate produce 2 Acetyl CoA (& 2 NADH): 2 X 3 = 6 ATP
2 Acetl CoA in citric acid cycle: 2 X 12 = 24 ATP

11. Energy yield of
aerobic glycolysis
2 Lactate
Oxygen
&
Mitochondria
No Oxygen
No Mitochondria
OR BOTH
GLUCOSE
2 PYRUVATE
2NAD+
2 NADH
= 2 X 3 = 6 ATP
2 ACETYL CoA
CITRIC ACID CYCLE
= 2 X 12 = 24 ATP
2NAD+
2 NADH
= 2 X 3 = 6 ATP
Energy yield of
anaerobic glycolysis
2 ATP
Net = 2 ATP/ glucose molecule
Net = 38 ATP / glucose molecule

12. Oxidative phosphorylation:
The formation of high-energy phosphate bonds by phosphorylation of ADP to ATP
coupled to the the electron transport chain (ETC) that occurs in the mitochondria.
Substrate-level phosphorylation:
The formation of high-energy phosphate bonds by phosphorylation of ADP to ATP
(or GDP to GTP)
It is coupled to cleavage of a high-energy metabolic intermediate (substrate).
It may occur in cytosol or mitochondria
Example: in glycolysis ATPs are produced
ENERGY PRODUCTION
Oxidative phosphorylation & Substrate-level
phosphorylation

13. Regulation of key enzyme of glycolysis
The regulation of the activity of key enzyme is conducted through:
1- General: (occurs in all types of enzymes in the body)
increasing substrate concentration will lead to increase activity of the
enzyme
2-Special regulatory mechanisms:
i- Allosteric effectors
ii- Covalent modification
iii. Induction/Repression of enzyme synthesis( long –term regulation)

14. Example of Covalent Modification
(short-term regulation)

15. Long-term Regulation
of glycolysis
Induction & Repression
of enzymes synthesis
Insulin: Induction
Glucagon: Repression

16. Genetic defects of glycolytic enzymes
Pyruvate kinase deficiency
Pyruvate kinase (PK) deficiency leads to a reduced rate of glycolysis with
decreased ATP production.
PK deficiency effect is restricted RBCs.
As RBCs have no mitochondria & so get ATP only from glycolysis.
RBCs needs ATP mainly for maintaining the bio- concave flexible shape of the cell.
PK deficiency leads to severe deficiency of ATP for RBCs. So, RBCs fail to maintain
bi-concave shape ending in liability to be lysed (hemolysis).
Excessive lysis of RBCs leads to chronic hemolytic anemia.