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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

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glycolysis
Glycolysis

Glycolysis is the breakdown of glucose to:

1- Provide energyin the form of ATP (main function)

2- Provide intermediatesfor other metabolic pathways.

It occurs in cytosolsof all tissues

All sugars can be converted to glucose & thus can be metabolized by glycolysis.

end products of 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)

glycolysis1
Glycolysis

Glucose (6C)

2 ATP

4 ADP

2 ADP

4 ATP

2 NAD

2 NADH+ H+

2 Pyruvate (3C)

glycolysis2
Glycolysis

Glucokinase or hexokinase

end products of glycolysis1
End products of glycolysis

AEROBIC GLYCOLYSIS

Mitochondria & Oxygen

NADH

is an end product

of aerobic glycolysis

ANAEROBIC GLYCOLYSIS

No mitochondria

No Oxygen

Or Both

Pyruvate

is the end product

of aerobic glycolysis

Lactate

is the end product

of anaerobic glycolysis

key enzymes in glycolysis
Key enzymes in glycolysis

1-Hexokinase & Glucokinase

Glucose Glucose6-phosphate

2-Phosphofructokinase (PFK)

Fructose 6-phosphate Fructose 1,6 bisphosphate

3-Pyruvate Kinase (PK)

Phosphoenel pyruvate Pyruvate

slide13

Key enzymes in glycolysis

Steps catalyzed

By

key enzymes

ONE WAY REACTIONS

1

2

3

energy yield from glycolysis
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 X 3 ATPs for each NADH entering electric transport chain (ETC) in mitochondria.

energy yield from glycolysis1
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 AcetlCoA in citric acid cycle: 2 X 12 = 24 ATP

slide16

Energy yield of

aerobic glycolysis

Energy yield of

anaerobic glycolysis

GLUCOSE

Net = 38 ATP / glucose molecule

Net = 2 ATP/ glucose molecule

2NAD+

2 ATP

2 NADH

= 2 X 3 = 6 ATP

No Oxygen

No Mitochondria

OR BOTH

Oxygen

&

Mitochondria

2 Lactate

2 PYRUVATE

2NAD+

2 NADH

= 2 X 3 = 6 ATP

2 ACETYL CoA

CITRIC ACID CYCLE

= 2 X 12 = 24 ATP

energy production oxidative phosphorylation substrate level phosphorylation
ENERGY PRODUCTIONOxidative 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-levelphosphorylation: 

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 k ey e nzyme of glycolysis
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)

long term regulation of glycolysis induction respression of enzymes synthesis
Long-term Regulation of glycolysisInduction & Respressionof enzymes synthesis

Insulin: Induction

Glucagon: Repression

genetic defects of glycolytic enzymes
Genetic defects of glycolytic enzymes

Pyruvate kinase deficiency

Pyruvatekinase (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.