8.1 Enzymes HL

• most metabolic pathways involve a chain of reactions • some metabolic pathways form a cycle instead and in this type of pathway, end product of one reaction is the reactant that starts the rest of the pathway

• energy necessary for reaciton to occur as it is used to weaken/break bonds in substrate

• the binding of substrate to active site of enzyme lowers the overall energy level of transition state & reduces the activation energy

• chemical substances that bind to enzymes & reduce the activity of enzyme

• competitive inhibitors: interfere w/ active site -> substrate can’t bind to active site • non-competitive inhibitors: bind at a location other than active site (allosteric sites) -> substrate can’t bind to active site / reaction is slowed

• sulfadiazine: blocks para-aminobenzoate from binding to dihydropteroate synthetase

• xylitol-5-phosphate: blocks fructose-6-phosphate from binding to phosphofructokinase

• regulation of enzyme by binding effector molecule at a site other than active site

enzyme that is regulated catalyzes one of the first reactions in metabolic pathway & substance that binds to allosteric site is the end product of the pathway - end product acts as inhibitor

• economical way to control metabolic pathways: • allows concentration of the end product to be controlled • increase in concentration of product causes reaction to eventually slow down and stop because reactions often reach equilibrium position instead of going to completion -> this reverberates back through metabolic pathway when end product accumulates w/ all intermediates accumulating • end-product inhibition prevents this build-up of intermediate products

• through a series of 5 reactions, amino acid threonine is converted to isoleucine • as concentration of isoleucine builds up, it binds to allosteric site of first enzyme in the chain, threonine deaminase <- isoleucine acts as non-competitive inhibitor

conc of isoleucine increases -> isoleucine binds to allosteric site of first enzyme in chain, threonine deaminase (isoleucine acts as non-competitive inhibitor)

• increasing resistance of Plasmodium falciparum (pathogen that causes malaria) to anti-malarial drugs such as chloroquine • dependence of all new drug combinations on narrow range of medicines • increasing global efforts to eradicate malaria

Plasmodium falciparum strain 3D7: variety of the malarial parasite for which the genome has been sequenced

• competitive inhibitor: concentration of substrate begins to exceed the amount of inhibitor -> maximum rate of uninhibited enzyme can be achieved BUT takes much higher concentration of substrate to achieve this maximum rate • non-competitive inhibitor: enzyme doesn’t react the same maximum rate bc binding of non-competitive inhibitor prevents some enzymes from being able to react regardless of substrate concentration -> enzymes that don’t bind to inhibitors follow same pattern as normal enzyme -> takes approximately same conc of enzyme to reach maximum rate, but max rate is lower than uninhibited enzyme

1) measuring the rate of disappearance of substrate 2) measuring the rate of appearance of product

amount of reaction per unit time e.g. %/s

• bioinformatics: approach whereby multiple research groups can add information to a database enabling other groups to query the database • chemogenomics: one promising bioinformatics technique that has facilitated research into metabolic pathways • scientists look to develop new drugs and test massive libraries of chemicals on a range of organisms to find which ones are effective on particular parts of different metabolic pathways • there’s often a huge database and metabolic pathways they affect