Mechanism of action of enzymes and Biological and pharmaceutical applications of some enzymes..pptx

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1. BIOCHEMISTRY PRESENTATION GROUP MEMBERS ●MUHAMMAD AKMAL ●MUHAMMAD MOHSIN ●HASAAN MAKHDOOM ●ALI RAZA ●SYED MUHAMMAD ALI PRESENTED TO Dr. ASAD ALI ARIF (HOD Department of Pharmacy) MUSLIM INSTITUTE OF EDUCATION

2. M ECHANISM OF ENZYME ACTION

3. M ECHANISM OF ENZYME ACTION ● The catalytic efficiency of enzymes is explained by two perspectives: Thermodynamic changes Processes at the active site

4. T HERMODYNAMIC CHANGES ● All chemical reactions have energy barriers between reactants and products. ● The difference in transitional state and substrate is called activational barrier .

5. T HERMODYNAMIC CHANGES ● Only a few substances cross the activation barrier and change into products. ● That is why rate of uncatalyzed reactions is much slow. ● Enzymes provide an alternate pathway for conversion of substrate into products. ● Enzymes accelerate reaction rates by forming transitional state having low activation energy. ● Hence, the reaction rate is increased many folds in the presence of enzymes. ● The total energy of the system remains the same and equilibrium state is not disturbed.

6. T HERMO - DYNAMIC CHANGES OVERVIEW

7. P ROCESSES AT THE ACTIVE SITE Covalent catalysis Acid base catalysis Catalysis by strain Catalysis by proximity

8. C OVALENT CATALYSIS ● Enzymes form covalent linkages with substrate forming transient enzyme-substrate complex with very low activation energy. ● Enzyme is released unaltered after completion of reaction.

9. ACID - BASE CATALYSIS ● Mostly undertaken by oxido- reductases enzyme. ● Mostly at the active site, histidine is present which act as both proton donor and proton acceptor.

10. C ATALYSIS BY PROXIMITY ● In this catalysis molecules must come in bond forming distance. When enzyme binds: ●This will orient substrate molecules especially in a position ideal for them. ● A region of high substrate concentration is produced at active site.

11. C ATALYSIS BY BOND STRAIN ● Mostly undertaken by lyases. ● The enzyme-substrate binding causes re-orientation of the structure of site due to in a strain condition. ● Thus transitional state is required and here bond is unstable and eventually broken. ● In this way bond between substrate is broken and converted into products.

12. L OCK AND KEY MODEL ● Proposed by EMIL FISCHER in 1894. ● Lock and key hypothesis assumes the active site of an enzymes are rigid in its shape. ● There is no change in the active site before and after a chemical reaction

13. I NDUCED FIT MODEL ● More recent studies have revealed that the process is much more likely to involve an induced fit model(proposed by DANIEL KOSH LAND in 1958 ). ● According to this exposure of an enzyme to substrate cause a change in enzyme, which causes the active site to change its shape to allow enzyme and substrate to bind.

14. BIOLOGICAL AND PHARMACEUTICAL IMPORTANCE OF ENZYMES

15. Use of Enzymes In Medicine and Pharmacy ●Diabetics use strips of paper fertilised with aldohexose enzyme to observe their glucose. ●Enzymes like pancrelipase (which contains amylase, lipase, and protease) are administered orally to aid in the digestion of carbohydrates, fats, and proteins. ●Enzymes such as creatine kinase (CK), lactate dehydrogenase (LDH), and amylase are measured in blood tests to diagnose and monitor various medical conditions, including heart attacks, liver disease, and pancreatitis, respectively. ●Cytochrome P450 monooxygenases are employed in the synthesis of various drugs, including antibiotics and anticancer agents, through biotechnological processes.

16. ●Streptokinase converts plasminogen to plasmin, promoting fibrinolysis and dissolution of blood clots and used for treatment of acute myocardial infarction, deep vein thrombosis, and arterial thromboembolism. ●Mannitol increases osmotic pressure in the renal tubules, leading to increased water excretion and manage cerebral edema, acute glaucoma, and acute kidney injury. ●Lipase Inhibitors (Orlistat) inhibits pancreatic lipase enzyme, reducing the absorption of dietary fats used for treatment of obesity as an adjunct to diet and exercise. ●Dornase alfa is used for management of cystic fibrosis to improve airway clearance and reduce pulmonary exacerbations. ●Alpha-galactosidase A is used for treatment of Fabry disease, a lysosomal storage disorder.

17. ●Asparaginase Erwinia chrysanthemi is used for treatment of acute lymphoblastic leukemia (ALL) in patients allergic to Escherichia coli-derived asparaginase. ●Collagenase is used for treatment of chronic wounds including diabetic ulcers, pressure ulcers, and burns. ●L-asparaginase is used for treatment of acute lymphoblastic leukemia (ALL) and certain other hematological malignancies. ● Prolactazyme treats lactose intolerance.