Transcript Glycolysis

Introduction of Glucose Metabolism
Lecture-2
Glycolysis
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.
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)
Overall reactions of glycolysis
Glycolysis
Glucose (6C)
2 ATP
4 ADP
2 ADP
4 ATP
2 NAD
2 NADH+ H+
2 Pyruvate (3C)
End products of glycolysis
AEROBIC GLYCOLYSIS
Mitochondria & Oxygen
ANAEROBIC GLYCOLYSIS
No mitochondria
No Oxygen
Or Both
Lactate
is the end product
of anaerobic glycolysis
NADH
is an end product
of aerobic glycolysis
Pyruvate
is the end product
of aerobic glycolysis
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
Key enzymes in glycolysis
1
2
Steps catalyzed
By
key enzymes
ONE WAY REACTIONS
3
Energy yield from glycolysis
1- Anerobic 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.
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
Energy yield of
aerobic glycolysis
Net = 38 ATP / glucose molecule
GLUCOSE
Energy yield of
anaerobic glycolysis
Net = 2 ATP/ glucose molecule
2NAD+
2 ATP
Oxygen
&
Mitochondria
2 NADH
= 2 X 3 = 6 ATP
No Oxygen
No Mitochondria
OR BOTH
2 PYRUVATE
2NAD+
2 NADH
= 2 X 3 = 6 ATP
2 ACETYL CoA
CITRIC ACID CYCLE
= 2 X 12 = 24 ATP
2 Lactate
ENERGY PRODUCTION
Oxidative phosphorylation & Substrate-level
phosphorylation
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
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)
Example of Covalent Modification
(short-term regulation)
Long-term Regulation
of glycolysis
Induction & Respression
of enzymes synthesis
Insulin: Induction
Glucagon: Repression
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 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.