Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS...

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Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

Transcript of Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS...

Page 1: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

Metabolism

Dr. Samah KotbLecturer of Biochemistry

2015

Cellular Biochemistry and

Metabolism(CLS 331)

Page 2: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

Metabolism

Metabolism is the study of the chemical reactions that occur

inside living cells. Updates over 2000 such reactions have been

documented. Although this is a large number, there is a high

degree of organization and order that govern these reactions.

Metabolic reactions do not occur at random inside cells but take

the shape of chains or series known as Metabolic Pathways.

Some pathways are short made of 2 or 3 reactions or long

made of 20, 30 or 40 reactions.

Page 3: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

• A metabolic pathway can be defined as a specific sequence of enzymatically catalyzed reactions in which the product of one reaction serves as the substrate of the next reaction in the chain. The following is an example of a metabolic pathway made of six reactions:-

Metabolism

Page 4: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

Shapes of Metabolic Pathways

A. Linear

B. Branched

C. Cyclic

Page 5: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

There are 2 types of metabolic pathways that occur inside

cells:-

1) Catabolic Pathways

These are made of reactions through which energy rich

nutrient molecules are broken down by chemical

reactions into simple end products. As a result of catabolic

pathways energy is produced and released to the cell.

Types of Pathways

Page 6: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

• 1) Catabolic Pathways

Types of Pathways

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2) Anabolic Pathways:

These are pathways made of reactions that result in the

synthesis of biomolecules using basic unit components.

These biomolecules are either biologically or structurally

important to the cells.

Anabolic reactions & pathways require an input of energy

to take place.

Types of Pathways

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• 2) Anabolic Pathways:•

Page 9: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

Link between Catabolism & Anabolism:

Page 10: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

Stages of catabolism

Page 11: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

1. Stage1: Digestion:- Hundreds of proteins and many kinds

of polysaccharides & lipids are broken down chemically or

enzymatically into their building block units.

2. Stage 2: Intracellular:- The building block units arrive

inside cells from the blood. They are degraded via Catabolic

Pathways into a common product namely acetyl-CoA.

3. Stage 3: Intracellular:- Acetyl-CoA is completely degraded

into CO2 and H2O via reactions of the TCA cycle.

Stages of catabolism

Page 12: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

The energy of catabolism is used by cells to drive

various activities that require expenditure of energy.

The energy of Catabolism

Page 13: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

Cells use 3 mechanisms to regulate (speed up or slow

down) the rate of metabolic activity:-

1) Allosteric enzymes.

2) Availability of enzymes.

3) Hormonal regulation.

Regulation of Cellular Metabolism

Page 14: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

• 1) Allosteric Regulation:

This is done by the use of allosteric enzymes which are usually

key enzymes of metabolic pathway.

Structure of allosteric enzymes:-

Enzymes are globular proteins made of peptide chains

that have folded on each other in a specific manner that

results in the formation of a globular macro protein with

an active site at the periphery of the protein molecule.

Metabolism and biochemical pathways

Page 15: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

• 1) Allosteric Regulation:

Regulation of Cellular Metabolism

Page 16: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

Allosteric modulators are of 2 types:-

i. An allosteric stimulator module of the enzyme.

ii. An allosteric inhibitor molecule of the enzyme.

Allosteric regulation mechanism

Page 17: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

• As the pathway occurs at a fast rate there will be accumulation of the end product G. When the levels of G reach a certain high level within the cell it will act as an allosteric inhibitor of E1 by binding to the allosteric site of the enzyme. Thus the catalysis of the reaction A B will be switched off thereby slowing down the whole pathway. Note that E1 is the key enzyme of the overall pathway.

Allosteric regulation mechanism

Page 18: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

With time the levels of G will start dropping as it

leaves the cell. Thus the allosteric inhibition of E1 is

removed and the enzyme restores its catalytic activity.

In other cases of allosteric inhibition the end product

is not involved. Instead a side product of the pathway

acts as the allosteric modulator. In many cases this

side product is the ATP/ADP level inside the cell.

Allosteric regulation mechanism

Page 19: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

Allosteric regulation mechanism

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Regulation of Cellular Metabolism

2) Availability of enzymesUpon consumption of a meal rich in carbohydrate and as digestion

in the GIT occurs, large amounts of glucose will be absorbed into the

blood. As a result there will be an influx of glucose into cells. Cells

react by synthesizing larger than usual amounts of glucose

degradative enzymes in order to increase the rate of its catabolism.

The levels of amino acids (a.a.) catabolic enzymes or fatty acids (f.a.)

catabolic enzymes stays normal. If the meal was rich in proteins, a.a.

catabolic enzymes will be synthesized in large amounts.

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Regulation of Cellular Metabolism

•Hormones are organic type molecule synthesized and secreted by special

type tissues known as endocrine glands.

• The hormones pour from the gland directly in to the blood and are

transported in the blood until they reach what is known as target tissue

cells.

• The hormone is recognized by its target cells; by way of receptors

present the outer surface of the cell membrane. As a result of the binding

between the hormone and its receptor a series of chemical reactions

inside the cell occurs that result in either an increase or a decrease in the

rate of a certain biochemical pathway.

3) Hormonal Regulation:

Page 22: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

Regulation of Cellular Metabolism

3) Hormonal Regulation

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Regulation of Cellular Metabolism

Adrenaline is a hormone synthesized and secreted by the

adrenal medullary cells. Adrenaline leaves the gland and is

transported in the blood until it reaches its target cells which

are liver and muscle cells. As the hormone binds to its target

cells large amounts of an intracellular secondary messenger

(Cyclic AMP) are synthesized. This will cause an increase in

the catabolic pathway responsible for breaking down

Glycogen into glucose (G).

3) Example for the Hormonal Regulation

Page 24: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

Regulation of Cellular Metabolism

• The extra glucose leaves muscle and liver & is distributed to the various tissues. Adrenaline is released from the adrenal medulla under conditions of emotional or physical stress. The body under such conditions requires extra catabolism of glucose for extra energy production.

Page 25: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)

Regulation of Cellular Metabolism

Other Hormones include:-

Insulin synthesized and secreted by the β cells of the

pancreas. Its target cells include muscle & adipose tissue.

It acts to lower plasma glucose levels by:

1. Increase the rate of glycolysis.

2. Increase the rate of glycogenesis.

3. Increase the rate of entry of glucose into cells.

Page 26: Metabolism Dr. Samah Kotb Lecturer of Biochemistry 2015 Cellular Biochemistry and Metabolism (CLS 331)