Introduction of Glucose Metabolism
Lecture-2

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.

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)

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

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

2
1
3
Steps catalyzed
By
ONE WAY REACTIONS

1Anerobic 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 in
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 electric transport chain (ETC) in mitochondria.

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

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

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

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)

Example of Covalent Modification
(short-term regulation)

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

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 has 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.