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1 Catalysis by Enzymes
Enzyme: A protein or other molecule that acts as a catalyst for a biological reaction. Active site: A pocket in an enzyme with the specific shape and chemical makeup necessary to bind a substrate. Substrate: A reactant in an enzyme-catalyzed reaction.
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Specificity (enzyme): The limitation of the activity of an enzyme to a specific substrate, specific reaction, or specific type of reaction. The enzyme papain from papaya fruit catalyzes the hydrolysis of peptide bonds in many locations. Thrombin is specific for catalyzing hydrolysis of a peptide bond adjacent to arginine and does so primarily in a protein essential to blood clotting. Catalase is almost completely specific for one reactionthe decomposition of hydrogen peroxide.
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The specificity of an enzyme for one of two enantiomers is a matter of fit. A chiral reactant fits a chiral reaction site. The enantiomer at the top fits the reaction site like a hand in a glove, but the enantiomer at the bottom does not. The enzyme lactate dehydrogenase catalyzes the removal of hydrogen from L-lactate but not from D-lactate.
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Catalytic activity is measured by turnover number, the maximum number of substrate molecules acted upon per enzyme per unit time. Most enzymes turn over 101000 molecules per second.
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Trace minerals and certain vitamins are a dietary necessity because they function as building blocks for cofactors and we cannot synthesize them.
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Transferases catalyze transfer of a group from one molecule to another. Kinases transfer a phosphate group from ATP to give ADP and a phosphorylated product.
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Hydrolases catalyze the breaking of bonds with addition of water. The digestion of carbohydrates and proteins by hydrolysis requires these enzymes.
Ligases catalyze the bonding together of two substrates. Such reactions are generally not favorable and require energy from ATP hydrolysis.
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Isomerases catalyze the isomerization (rearrangement of atoms) of a substrate in reactions that have but one substrate and one product.
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Lyases catalyze the addition of a molecule to a double bond or the reverse reaction in which a molecule is eliminated from a double bond.
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Enzymes have the family-name ending -ase. Exceptions occur for enzymes such as papain and trypsin, which are still referred to by older common names. Modern systematic names always have two parts: - the first identifies the substrate on which the enzyme operates - the second part is an enzyme subclass name like those shown on the next slide. Example: Pyruvate carboxylase is a ligase that acts on the substrate pyruvate to add a carboxyl group.
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The induced-fit model model of enzyme action has a flexible active site that changes shape to best fit the substrate and catalyze the reaction.
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Hydrolysis of a peptide bond by chymotrypsin. (a) The polypeptide enters the active site (b) Hydrogen transfer allows formation of a strained intermediate (c) The peptide bond is broken.
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Enzymes act as catalysts because of their ability to: Bring substrate(s) and catalytic sites together (proximity effect). Hold substrate(s) at the exact distance and in the exact orientation necessary for reaction (orientation effect). Provide acidic, basic, or other types of groups required for catalysis (catalytic effect). Lower the energy barrier by inducing strain in bonds in the substrate molecule (energy effect).
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At low substrate concentration, the reaction rate is directly proportional to the substrate concentration. With increasing substrate concentration, the rate drops off as more of the active sites are occupied. With all active sites occupied, the rate reaches a maximum.
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In the presence of excess substrate, the concentration of an enzyme can vary according to our metabolic needs. If the concentration of substrate does not become a limitation, the reaction rate varies directly with the enzyme concentration.
Prentice Hall 2007
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(a) The rate increases with increasing temperature until the protein begins to denature; then the rate decreases rapidly. (b) The optimum activity for an enzyme occurs at the pH where it acts.
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Feedback control: Regulation of an enzymes activity by the product of a reaction later in a pathway. If a product near the end of a metabolic pathway inhibits an enzyme that functions near the beginning of that pathway, then no energy is wasted making the ingredients for a plentiful substance. Allosteric control: An interaction in which the binding of a regulator at one site on a protein affects the proteins ability to bind another molecule at a different site.
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Allosteric control can be either positive or negative. Binding a positive regulator changes the active sites so that the enzyme becomes a better catalyst and the rate accelerates. Binding a negative regulator changes the active sites so that the enzyme is a less effective catalyst and the rate slows down.
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A competitive inhibitor can eventually be overcome by higher substrate concentrations. With a noncompetitive inhibitor the maximum rate is lowered for all substrate concentrations.
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Hg+2 and Pb+2 ions are irreversible inhibitors that bond to the S atoms in cysteine residues. Organophosphorus insecticides such as parathion and malathion, and nerve gases like Sarin are irreversible inhibitors of the enzyme acetylcholinesterase.
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Enzymes that cause blood clotting or digest proteins are examples of enzymes that must not be active at the time and place of their synthesis.
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Glycogen phosphorylase, the enzyme that initiates glycogen breakdown, is more active when phosphorylated. When glycogen stored in muscles must be hydrolyzed to glucose for quick energy, two serine residues are phosphorylated. The groups are removed once the need to break down glycogen for quick energy has passed.
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19.10 Vitamins
Vitamin: An organic molecule, essential in trace amounts that must be obtained in the diet because it is not synthesized in the body. Scurvy, pellagra, and rickets are caused by deficiencies of vitamins. Vitamins are grouped by solubility into two classes: water-soluble and fat-soluble. Some vitamins are valuable as antioxidants.
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Water soluble vitamin C is biologically active without any change in structure, biotin is connected to enzymes by an amide bond at its carboxyl group but otherwise undergoes no structural change from dietary biotin.
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The fat-soluble vitamins A, D, E, and K are stored in the bodys fat deposits. Although the clinical effects of deficiencies of these vitamins are well documented, the molecular mechanisms by which they act are not nearly as well understood as those of the water-soluble vitamins. None has been identified as a coenzyme. The hazards of overdosing on fat-soluble vitamins are greater than those of the water-soluble vitamins because of their ability to accumulate in body fats. Excesses of the water-soluble vitamins are more likely to be excreted in the urine.
Prentice Hall 2007
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An antioxidant is a substance that prevents oxidation. In the body, we need protection against active oxidizing agents that are by-products of normal metabolism. Our principal dietary antioxidants are vitamin C, vitamin E, b-carotene, and the mineral selenium. They work together to defuse the potentially harmful action of free radicals, highly reactive molecular fragments with unpaired electrons.
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