Enzymes Biological catalysts u u proteins RNA facilitate

Enzymes § Biological catalysts u u proteins (& RNA) facilitate chemical reactions § increase rate of reaction without being consumed § reduce activation energy § don’t change free energy ( G) released or required u u required for most biological reactions highly specific § thousands of different enzymes in cells u control reactions of life

Enzymes vocabulary substrate § reactant which binds to enzyme § enzyme-substrate complex: temporary association product § end result of reaction active site § enzyme’s catalytic site; substrate fits into active site substrate enzyme active site products

Properties of enzymes § Reaction specific u each enzyme works with a specific substrate § chemical fit between active site & substrate w H bonds & ionic bonds § Not consumed in reaction u single enzyme molecule can catalyze thousands or more reactions per second § enzymes unaffected by the reaction § Affected by cellular conditions u any condition that affects protein structure § temperature, p. H, salinity

Naming conventions § Enzymes named for reaction they catalyze u u sucrase breaks down sucrose proteases break down proteins lipases break down lipids DNA polymerase builds DNA § adds nucleotides to DNA strand u pepsin breaks down proteins (polypeptides)

Lock and Key model § Simplistic model of enzyme action u substrate fits into 3 -D structure of enzyme’ active site § H bonds between substrate & enzyme u like “key fits into lock”

Induced fit model § More accurate model of enzyme action 3 -D structure of enzyme fits substrate u substrate binding cause enzyme to change shape leading to a tighter fit u § “conformational change” § bring chemical groups in position to catalyze reaction

How does it work? § Variety of mechanisms to lower activation energy & speed up reaction u synthesis § active site orients substrates in correct position for reaction w enzyme brings substrate closer together u digestion § active site binds substrate & puts stress on bonds that must be broken, making it easier to separate molecules

Factors that Affect Enzymes

Factors Affecting Enzyme Function § Enzyme concentration § Substrate concentration § Temperature § p. H § Salinity § Activators § Inhibitors catalase

Enzyme concentration reaction rate What’s happening here? ! enzyme concentration

Factors affecting enzyme function § Enzyme concentration u as enzyme = reaction rate § more enzymes = more frequently collide with substrate u reaction rate levels off reaction rate § substrate becomes limiting factor § not all enzyme molecules can find substrate enzyme concentration

Substrate concentration reaction rate What’s happening here? ! substrate concentration

Factors affecting enzyme function § Substrate concentration u as substrate = reaction rate § more substrate = more frequently collide with enzyme u reaction rate levels off reaction rate § all enzymes have active site engaged § enzyme is saturated § maximum rate of reaction substrate concentration

Temperature reaction rate What’s happening here? ! 37° temperature

Factors affecting enzyme function § Temperature u Optimum T° § greatest number of molecular collisions § human enzymes = 35°- 40°C w body temp = 37°C u Heat: increase beyond optimum T° § increased energy level of molecules disrupts bonds in enzyme & between enzyme & substrate w H, ionic = weak bonds u § denaturation = lose 3 D shape (3° structure) Cold: decrease T° § molecules move slower § decrease collisions between enzyme & substrate

Enzymes and temperature § Different enzymes function in different organisms in different environments reaction rate human enzyme hot spring bacteria enzyme 37°C temperature 70°C (158°F)

p. H What’s happening here? ! trypsin reaction rate pepsin trypsin 0 1 2 3 4 5 6 p. H 7 8 9 10 11 12 13 14

Factors affecting enzyme function § p. H u changes in p. H § adds or remove H+ § disrupts bonds, disrupts 3 D shape w disrupts attractions between charged amino acids w affect 2° & 3° structure w denatures protein u optimal p. H? § most human enzymes = p. H 6 -8 w depends on localized conditions w pepsin (stomach) = p. H 2 -3 w trypsin (small intestines) = p. H 8 0 1 2 3 4 5 6 7 8 9 10 11

Salinity reaction rate What’s happening here? ! salt concentration

Factors affecting enzyme function § Salt concentration u changes in salinity § adds or removes cations (+) & anions (–) § disrupts bonds, disrupts 3 D shape w disrupts attractions between charged amino acids w affect 2° & 3° structure w denatures protein u enzymes intolerant of extreme salinity § Dead Sea is called dead for a reason!

Compounds which help enzymes Fe in § Activators hemoglobin u cofactors § non-protein, small inorganic compounds & ions w Mg, K, Ca, Zn, Fe, Cu w bound within enzyme molecule u coenzymes § non-protein, organic molecules w bind temporarily or permanently to enzyme near active site § many vitamins w NAD (niacin; B 3) w FAD (riboflavin; B 2) w Coenzyme A Mg in chlorophyll

Compounds which regulate enzymes § Inhibitors molecules that reduce enzyme activity u competitive inhibition u noncompetitive inhibition u irreversible inhibition u feedback inhibition u

Competitive Inhibitor § Inhibitor & substrate “compete” for active site Examples: u penicillin blocks enzyme bacteria use to build cell walls u disulfiram (Antabuse) treats chronic alcoholism u § blocks enzyme that breaks down alcohol

Non-Competitive Inhibitor § Inhibitor binds to site other than active site u u allosteric inhibitor binds to allosteric site causes enzyme to change shape § conformational change § active site is no longer functional binding site w keeps enzyme inactive Examples: some anti-cancer drugs inhibit enzymes involved in DNA synthesis § stop DNA production § stop division of more cancer cells

Irreversible inhibition § Inhibitor permanently binds to enzyme u competitor § permanently binds to active site u allosteric § permanently binds to allosteric site § permanently changes shape of enzyme

Feedback Inhibition § Used to control metabolic pathways involving a series of reactions u u Product formed later in the sequence, allosterically inhibits an enzyme that catalyzes a reaction earlier in the sequence. no unnecessary accumulation of product A B C D E F G 1 2 3 4 5 6 X enzyme enzyme allosteric inhibitor of enzyme 1

Allosteric Regulation Summary: § Conformational changes by regulatory molecules u inhibitors § keeps enzyme in inactive form u activators § keeps enzyme in active form Conformational changes Allosteric regulation

Homework § Read and make notes on Enzymes ( 1. 3) § Complete pg. 42 #1 -9