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Download Chapter 20 Enzymes and Vitamins
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Names of Enzymes The name of an enzyme •Usually ends in ase. •Identifies the reacting substance. For example, sucrase catalyzes the hydrolysis of sucrose. • Describes the function of the enzyme. For example, oxidases catalyze oxidation. • Can be a common name, particularly for the digestive enzymes, such as pepsin and trypsin. Enzyme Classification Enzymes are classified by the type of reaction they catalyze. Oxidoreductases Catalyze oxidation-reduction reactions Transferases Catalyze transfer of groups between compounds alanine transaminase alanine -ketoglutarate O NH2 CH3CCO2 + O2CCH2CH2CHCO2 pyruvate glutamate Enzyme Classification Hydrolyases Catalyze hydrolysis reactions R N CH H R O C N CH CO2 + H2O peptidase H Lyases Catalyze addition or removal of groups without hydrolysis or oxidation Enzyme Classification Isomerases Catalyze rearrangement reactions triose phosphate isomerase glyceraldehyde-3-phosphate dihydroxyacetone phosphate Ligases Catalyze reactions that connect molecules - requires energy input O CH3CCO2 + CO2 + ATP pyruvate pyruvate carboxylase O + O2C CH2CCO2 + ADP + Pi + H oxaloacetate Enzyme Cofactors • A simple enzyme is an active enzyme that consists only of protein. • Many enzymes are active only when they combine with cofactors such as metal ions or small molecules. • A coenzyme is a cofactor that is a small organic molecule such as a vitamin. • A holoenzyme is the enzyme + cofactor, an apoenzyme is the enzyme – cofactor. Metal Ions as Cofactors Many active enzymes require a metal ion. Zn2+, a cofactor for carboxypeptidase, stabilizes the carbonyl oxygen during the hydrolysis of a peptide bond. Water-Soluble Vitamins Water-soluble vitamins are • Soluble in aqueous solutions. • Cofactors for many enzymes. • Not stored in the body. Thiamine (Vitamin B1) Coenzyme form - thiamine pyrophosphate Coenzyme for decarboxylation reactions Nutritional sources: milk, grains, green vegetables Deficiency disease: beriberi Riboflavin (Vitamin B2) Coenzyme form - FAD Coenzyme for oxidation-reduction reactions Nutritional sources: milk, grains, green vegetables Deficiency symptoms: dermatitis, tongue inflamation Niacin (Vitamin B3) Coenzyme forms - NAD+ and NADP+ Coenzyme for oxidation-reduction reactions Nutritional sources: milk, grains, green vegetables Deficiency disease: pellegra (rough skin) Pantothenic Acid (Vitamin B5) Coenzyme form - coenzyme A Coenzyme for transfer of acyl groups Nutritional sources: most foods Deficiency symptoms: fatigue, apathy, muscle cramps Pyridoxine (Vitamin B6) Coenzyme form - pyridoxal pyrophosphate Coenzyme for amino group transfer reactions Nutritional sources: milk, grains, green vegetables Deficiency symptom: dermatitis, anemia Biotin (Vitamin B7) Coenzyme form - biotin Coenzyme for carboxylation reactions Nutritional sources: milk, liver, also produced by intestinal bacteria Deficiency symptom: dermatitis Folic Acid (Vitamin B9) Coenzyme form - tetrahydrofolate Coenzyme for intermolecular one-carbon transfers Nutritional sources: green leafy vegetables, yeast, and produced by intestinal bacteria Deficiency symptoms: anemia, diarrhea Vitamin B12 Coenzyme form - 5’deoxyadenosylcobalamin Coenzyme for intramolecular rearrangements Nutritional sources: milk, eggs, other animal products Deficiency disease: pernicious anemia Vitamin C Coenzyme form - vitamin C Coenzyme for hydroxylation reactions Nutritional sources: citrus fruits, tomatoes, broccoli Deficiency disease: scurvy (weakened collagen) Zymogen Inactive precursor form of an enzyme or other protein Digestive enzymes pepsinogen trypsinogen pepsin trypsin chymotrypsinogen chymotrypsin procarboxypeptidase carboxypeptidase Blood-clotting proteins prothrombin fibrinogen Insulin proinsulin thrombin fibrin insulin Active Site The active site • Is a region within an enzyme that fits the shape of the reacting molecule called a substrate. • Contains amino acid R groups that bind the substrate. • Releases products when the reaction is complete. Enzyme Catalyzed Reaction: Basic Mechanism The proper fit of a substrate (S) in an active site forms an enzyme-substrate (ES) complex. E+S ES Within the ES complex, the reaction occurs to convert substrate to product (P). ES E+P The products, which are no longer attracted to the active site, are released. Overall, substrate is converted to product. E+S ES E+P Enzyme Catalyzed Reaction In an enzyme-catalyzed reaction • A substrate attaches to the active site. • An enzyme-substrate (ES) complex forms. • Reaction occurs and products are released. • An enzyme is used over and over. E+S ES E+ P Enzymes are Biological Catalysts Enzymes are proteins that • Catalyze nearly all the chemical reactions taking place in the cells of the body. • Increase the rate of reaction by providing pathway with a lower the energy of activation. Lock and Key Model In the lock-and-key model of enzyme action, • The active site has a rigid shape. • An enzyme only binds substrates that exactly fit the active site. • Only substrates with the matching shape can fit. • The substrate is the key that fits that lock. Induced-fit Model In the induced-fit model of enzyme action, • Enzyme structure is flexible, not rigid. • Enzyme and substrate adjust the shape of the active site to bind substrate. • Shape changes improve catalysis during reaction. • The range of substrate specificity increases. Enzyme Specificity Enzymes may recognize and catalyze • A single substrate. (absolute specificity) Example: urease • A specific stereoisomer (stereochemical specificity) Example: D-amino acid oxidase • A group of similar substrates.(group specificity) Example: alcohol dehydrogenase • A particular type of bond.(linkage specificity) Example: lipase Substrate Concentration An increase in substrate concentration • Increases the rate of reaction (at constant enzyme concentration). • Eventually saturates an enzyme with substrate to give maximum activity. Enzyme Concentration An increase in enzyme concentration • Increases the rate of reaction (at constant substrate concentration). • Binds more substrate with enzyme. Temperature and Enzyme Action Enzymes • Are most active at an optimum temperature (usually 37°C in humans). • Show little activity at low temperatures. • Lose activity at high temperatures as denaturation occurs. pH and Enzyme Action Enzymes • Are most active at optimum pH. • Contain R groups of amino acids with proper charges at optimum pH. • Lose activity in low or high pH as charges change. Optimum pH Values Enzymes in • The body have an optimum pH of about 7.4. • Certain organs, enzymes operate at lower and higher optimum pH values. Feedback Control (Feedback Inhibition) In feedback control • A product acts as a negative regulator. • As the concentration of the end product increases, the end product binds with the first enzyme (E1) in a sequence decreasing the rate of the first reaction. Specific Example of Feedback Inhibition Biosynthesis of Threonine Allosteric Enzymes An allosteric enzyme is • An enzyme in a reaction sequence that binds a regulator substance. • A positive regulator is one that enhances the binding of substrate and accelerates the rate of reaction. • A negative regulator when it prevents the binding of the substrate to the active site and slows down the rate of reaction. Irreversible Inhibition In irreversible inhibition, a substance • Bonds with R groups at the active site. • Destroys enzyme activity. Competitive Inhibition A competitive inhibitor • Has a structure that is similar to that of the substrate. • Competes with the substrate for the active site. • Has its effect reversed by increasing substrate concentration. Malonate and Succinate Dehydrogenase Malonate • Is a competitive inhibitor of succinate dehydrogenase. • Has a structure that is similar to succinate. • Inhibition is reversed by adding succinate. Noncompetitive Inhibition A noncompetitive inhibitor • Binds to a site other than the active site. • Alters the arrangement of groups in the active site. • Doesn’t prevent binding of the substrate, but blocks activity. • Cannot have its effect reversed by adding more substrate. Some Medical Uses of Inhibitors Cancer chemotherapy Methotrexate (amethopterin) - inhibits synthesis of thymine (part of DNA) 5-Fluorouracil - inhibits DNA synthesis Antibiotics Sulfa drugs - inhibits synthesis of folic acid Tetracyclines - inhibit protein synthesis Penicillin - inhibits bacterial cell wall synthesis Neural Transmission using Acetylcholine Release: inhibited by toxin from Clostridium botulinum Binding: inhibited by curare Breakdown: inhibition of acetylcholine esterase Inhibitors: nerve gases (sarin, tabun), insecticides (malathion, parathion) Isoenzymes Isoenzymes • Catalyze the same reaction in different tissues in the body. • Such as lactate dehydrogenase (LDH), which converts lactate to pyruvate, consists of five isoenzymes. • Can be used to identify the organ or tissue involved in damage or disease. • Such as LDH have one form more prevalent in heart muscle and another form in skeletal muscle and liver. Isoenzymes of Lactate Dehydrogenase Diagnostic Enzymes Levels of enzymes CK, LDH, and AST • Are elevated following a heart attack. • Are used to determine the severity of the attack. Diagnostic Enzymes Diagnostic enzymes • Determine the amount of damage in tissues. • That are elevated may indicate damage or disease in a particular organ. Enzyme Classification isomerase transferase Enzyme Classification oxidoreductase lyase Enzyme Classification ligase hydrolase