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

2. 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.

3. 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

4. Shapes of Metabolic Pathways A.Linear B.Branched C. Cyclic

5. 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

6. 1) Catabolic Pathways 1) Catabolic Pathways Types of Pathways

7. 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

8. 2) Anabolic Pathways: 2) Anabolic Pathways:

9. Link between Catabolism & Anabolism:

10. Stages of catabolism

11. 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 CO 2 and H 2 O via reactions of the TCA cycle. Stages of catabolism

12. The energy of catabolism is used by cells to drive various activities that require expenditure of energy. The energy of Catabolism

13. 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

14. 1) Allosteric Regulation: 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

15. 1) Allosteric Regulation: 1) Allosteric Regulation: Regulation of Cellular Metabolism

16. 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

17. 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 E 1 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 E 1 is the key enzyme of the overall pathway. Allosteric regulation mechanism

18.  With time the levels of G will start dropping as it leaves the cell. Thus the allosteric inhibition of E 1 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

20. Regulation of Cellular Metabolism 2) Availability of enzymes glucose degradative enzymes Upon 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.

21. 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 :

22. Regulation of Cellular Metabolism 3) Hormonal Regulation

23. 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

24. 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.

25. 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.