Metabolism (Enzymes)

Metabolism Enzymes Explain how enzymes catalyse chemical reactions Enzymes speed up the rate of a chemical reaction by lowering the activation energy threshold ………………………………………………………………………………………………………………………………………………….......... ………………………………………………………………………………………………………………………………………………….......... Distinguish between exergonic and endergonic reactions Exergonic reactions release energy (i.e. reactants have more stored energy than products) ………………………………………………………………………………………………………………………………………………….......... Endergonic reactions absorb energy (i.e. reactants have less stored energy compared to products) ………………………………………………………………………………………………………………………………………………….......... ………………………………………………………………………………………………………………………………………………….......... ………………………………………………………………………………………………………………………………………………….......... Inhibitors Outline, with the aid of a diagram, how a competitive inhibitor affects enzyme activity enzyme substrate inhibitor NO reaction A competitive inhibitor is similar in structure and chemical properties to the substrate ………………………………………………………………………………………………………………………………………………….......... It can bind to the active site and block substrate binding ………………………………………………………………………………………………………………………………………………….......... Increasing substrate concentrations will reduce the effect of a competitive inhibitor ………………………………………………………………………………………………………………………………………………….......... Give a specific example of a competitive inhibitor Relenza is a drug designed to treat infection with the influenza virus ………………………………………………………………………………………………………………………………………………….......... Influenza virions tether to infected cells via haemagglutinin and are released by the enzyme neuraminidase ………………………………………………………………………………………………………………………………………………….......... Relenza competitively inhibits the neuraminidase active site, preventing cleavage from haemagglutinin ………………………………………………………………………………………………………………………………………………….......... Thus virions cannot be released and the spread of infection is diminished ………………………………………………………………………………………………………………………………………………….......... Outline, with the aid of a diagram, how a non-competitive inhibitor affects enzyme activity enzyme substrate inhibitor NO reaction Non-competitive inhibitors bind to a site other than the active site (called an allosteric site) ………………………………………………………………………………………………………………………………………………….......... These inhibitors cause a conformational change in the enzyme, which alters the shape of the active site ………………………………………………………………………………………………………………………………………………….......... Thus the substrate can no longer bind (increasing substrate concentration will have no effect on inhibition) ………………………………………………………………………………………………………………………………………………….......... Give a specific example of a non-competitive inhibitor Cyanide binds to a carrier protein in the electron transport chain and causes a conformational change ………………………………………………………………………………………………………………………………………………….......... The carrier can no longer shuttle electrons, so oxidative phosphorylation (aerobic respiration) is shut down ………………………………………………………………………………………………………………………………………………….......... Without energy (ATP) the cells die, making cyanide a very potent poison ………………………………………………………………………………………………………………………………………………….......... ………………………………………………………………………………………………………………………………………………….......... On the graph below, show the impact of a competitive and non-competitive inhibitor on reaction rate Competitive inhibitor: • Rate of reaction is slowed (graph shifts right) ……………………………………………………………………………… Normal reaction (but requires higher substrate concentrations) ……………………………………………………………………………… ……………………………………………………………………………… Non-Competitive inhibitor: • Rate of reaction is slowed (graph shifts right) ……………………………………………………………………………… Rate of Reaction • Maximal rate of reaction is still achievable ……………………………………………………………………………… Competitive inhibitor Non-competitive inhibitor • Maximal rate of reaction is less (graph shifts down) ……………………………………………………………………………… • Increasing substrate concentration will not increase ……………………………………………………………………………… maximum reaction rate ……………………………………………………………………………… Substrate Concentration Outline, with the aid of a diagram, how metabolic pathways are controlled by end-product inhibition A B Enzyme 1 C Enzyme 2 D Enzyme 3 Negative feedback End-product inhibition (or feedback inhibition) is when a product of a metabolic pathway inhibits one of the ………………………………………………………………………………………………………………………………………………….......... enzymes involved in its production ………………………………………………………………………………………………………………………………………………….......... This allows reaction rates to be tightly regulated ………………………………………………………………………………………………………………………………………………….......... Give a specific example of end-product inhibition In plants and bacteria, isoleucine can be synthesised from threonine ………………………………………………………………………………………………………………………………………………….......... This multi-step reaction involves the enzyme threonine deaminase ………………………………………………………………………………………………………………………………………………….......... Isoleucine can bind to an allosteric site on threonine deaminase and non-competitively inhibit it ………………………………………………………………………………………………………………………………………………….......... Thus when isoleucine levels are high its production is reduced, but when levels are low, production proceeds ………………………………………………………………………………………………………………………………………………….......... ………………………………………………………………………………………………………………………………………………….......... Outline, with an example, how bioinformatic databases are used to identify potential new drugs Malaria is caused by the protozoan Plasmodia (whose metabolism is controlled by specific enzymes) ………………………………………………………………………………………………………………………………………………….......... Bioinformatic databases can be searched to identify molecules that structurally resemble specific substrates ………………………………………………………………………………………………………………………………………………….......... Combinatorial chemistry can then be used to modify these molecules to form effective inhibitors ………………………………………………………………………………………………………………………………………………….......... This modelling of desired chemicals is called rational drug design ………………………………………………………………………………………………………………………………………………….......... Identify an example of a metabolic pathway that forms a chain Glycolysis ………………………………………………………………………………………………………………………………………………….......... Identify an example of a metabolic pathway that forms a cycle Krebs cycle (citric acid cycle) or Calvin cycle …………………………………………………………………………………………………………………………………………………..........