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lecture 1 Enzymes.ppt

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Вiochemistry of enzymes Вiochemistry of enzymes

Enzyme Classifcation 1. Oxidoreductases 2. Transferases 3. Hydrolases 4. Lyases 5. Isomerases 6. Ligases Enzyme Classifcation 1. Oxidoreductases 2. Transferases 3. Hydrolases 4. Lyases 5. Isomerases 6. Ligases

The overall Coenzyme role Coenzyme A Activation and transfer of acyl groups Pyridoxal transfer The overall Coenzyme role Coenzyme A Activation and transfer of acyl groups Pyridoxal transfer phosphate of amino groups FAD Transfer of hydrogen (electrons) Vitamin precursor Pantothenic acid Pyridoxine - Vitamin B 6 Riboflavin Vitamin B 2

coenzyme binding domain inactive enzyme vitamin active enzyme coenzyme binding domain inactive enzyme vitamin active enzyme

Enzyme active site Enzyme active site

Molecule of trypsin with amino acid residues in the active site Molecule of trypsin with amino acid residues in the active site

Allosteric enzyme Allosteric enzyme

Multifunctional enzyme Multifunctional enzyme

Isozymes of lactate dehydrogenase Isozymes of lactate dehydrogenase

Multimolecular enzyme systems NADPH oxidase Multimolecular enzyme systems NADPH oxidase

Fumarate inner mitochondrial membrane Succinate matrix intermembrane space I, III and IV – mitochondrial Fumarate inner mitochondrial membrane Succinate matrix intermembrane space I, III and IV – mitochondrial respiratory chain complexes (the electron transport chain)

Hermann Emil Fischer (1852 - 1919) Hermann Emil Fischer (1852 - 1919)

Lock-and-key model by Fisher E + S E-S E + P Lock-and-key model by Fisher E + S E-S E + P

Daniel Koshland (1920 - 2007) Daniel Koshland (1920 - 2007)

Induced-fit theory by Koshlend Induced-fit theory by Koshlend

Substrate strain theory Substrate strain theory

Leonor Michaelis Maud Leonora Menten Leonor Michaelis Maud Leonora Menten

Equation of Michaelis - Menten Briggs – Haldane equation: Equation of Michaelis - Menten Briggs – Haldane equation:

Lineweaver – Burk plot Lineweaver – Burk plot

Urease CO(NH 2)2 + 2 H 2 O = H 2 O + Urease CO(NH 2)2 + 2 H 2 O = H 2 O +

Arginase Arginase

Pancreatic lipase Pancreatic lipase

Fumarase fumaric acid maleic acid Fumarase fumaric acid maleic acid

Regulation of enzyme activity Regulation of enzyme activity

Enzymatic activity IU = 1 mcmole/min 1 kat = 1 mole/sec 1 IU = Enzymatic activity IU = 1 mcmole/min 1 kat = 1 mole/sec 1 IU = 16. 67 nkat

Enzymes activated by metals Enzyme Cytochromes Peroxidase Amylase Phosphatase Cholinesterase Metal Fe Fe Ca Enzymes activated by metals Enzyme Cytochromes Peroxidase Amylase Phosphatase Cholinesterase Metal Fe Fe Ca Mg Mn

Competitive inhibition Competitive inhibition

succinate fumarate malonate succinate fumarate malonate

Competitive inhibition Competitive inhibition

p-aminobenzoic acid sulfanilamide p-aminobenzoic acid sulfanilamide

Non-competitive inhibition Non-competitive inhibition

Non-competitive inhibition Non-competitive inhibition

Un-competitive inhibition Un-competitive inhibition

Irreversible competitive inhibition Irreversible competitive inhibition

Irreversible competitive inhibition Irreversible competitive inhibition

Activation of the enzyme by phosphorylation Activation of the enzyme by phosphorylation

Regulation of activity by dissociation of the subunits of the enzyme Protein kinase Regulation of activity by dissociation of the subunits of the enzyme Protein kinase

Partial proteolysis inactive enzyme Partial proteolysis inactive enzyme

Allosteric regulation of enzyme activity Allosteric regulation of enzyme activity

Feedback inhibition Feedback inhibition

ENZYMES IN MEDICINE ENZYMES IN MEDICINE

Enzymes as therapeutic agents Enzyme The use of enzymes Trypsin, lipase, Disturbances of the Enzymes as therapeutic agents Enzyme The use of enzymes Trypsin, lipase, Disturbances of the amylase digestion Urease Removal of urea from the body in the "artificial kidney" Ribonuclease, Antiviral drugs against deoxyribonucle herpetic keratitis, ase adenoviral conjunctivitis Streptokinase, Preventing blood clots urokinase during operations

Enzymes as analytical agents Enzyme Glucose oxidase, peroxidase Lipase Cholesterol oxidase Various The use Enzymes as analytical agents Enzyme Glucose oxidase, peroxidase Lipase Cholesterol oxidase Various The use of enzyme Determination of glucose concentrations in the blood Determination of triacylglycerol concentration in the blood Determination of cholesterol in the blood Determination of pyruvate,

(stain) (stain)

Indicator enzymes Disease Myocardial infarction Liver diseases Pancreas diseases Enzyme aspartate transaminas e, LDH-1, Indicator enzymes Disease Myocardial infarction Liver diseases Pancreas diseases Enzyme aspartate transaminas e, LDH-1, creatine kinase alanine transaminase, aspartate transaminas e, -glutamyl transferase, alkaline phosphatase amylase, lipase, trypsin