Enzymes protein catalysts catalyst substrates products have great specificity for the reaction catalyzed and the molecules acted on catalyst substance that increases the rate of a reaction without being permanently altered substrates reacting molecules products substances formed by reaction

Structure and Classification of Enzymes some enzymes are composed solely of one or more polypeptides some enzymes are composed of one or more polypeptides and nonprotein components

Enzyme structure apoenzyme cofactor holoenzyme = apoenzyme + cofactor protein component of an enzyme cofactor nonprotein component of an enzyme prosthetic group – firmly attached coenzyme – loosely attached holoenzyme = apoenzyme + cofactor

Coenzymes often act as carriers, transporting substances around the cell

The Mechanism of Enzyme Reactions a typical exergonic reaction A + B  AB‡  C + D transition-state complex – resembles both the substrates and the products

activation energy – energy required to form transition- state complex without enzyme with enzyme enzyme speeds up reaction by lowering Ea

Interaction of enzyme and substrate catalytic site lock-and-key model

How enzymes lower Ea by increasing concentrations of substrates at active site of enzyme by orienting substrates properly with respect to each other in order to form the transition-state complex

The Effect of Environment on Enzyme Activity enzyme activity is significantly impacted by substrate concentration, pH, and temperature

Effect of [substrate] rate increases as [substrate] increases no further increase occurs after all enzyme molecules are saturated with substrate

Effect of pH and temperature each enzyme has specific pH and temperature optima denaturation loss of enzyme’s structure and activity when temperature and pH rise too much above optima

Enzyme Inhibition competitive inhibitor noncompetitive inhibitor directly competes with binding of substrate to active site noncompetitive inhibitor binds enzyme at site other than active site; changes enzyme’s shape so that it becomes less active Figure 8.19 – succinate dehydrogenase is inhibited by competitive inhibitor malonic acid

Control of Enzyme Activity allosteric regulation covalent modification feedback inhibition

Allosteric Regulation enzyme inactive – can’t bind substrate allosteric enzyme effector binding alters shape of active site example of a positive effector enzyme catalyzes reaction

An example – aspartate carbamoyltransferase (ACTase) from E. coli functions in pyrimidine synthesis Figure 8.24a: diagram showing 6 catalytic polypeptide chains and 6 regulatory chains; enzyme viewed from top Figure 8.24b: less active state of ACTase viewed from side Figure 8.24c: more active state of ACTase

ATP increases activity CTP decreases activity

CTP, a negative effector, increases the K0 CTP, a negative effector, increases the K0.5 value while ATP, a positive effector, lowers the K0.5. The Vmax remains constant.

Covalent Modification of Enzymes reversible addition or removal of a chemical group alters enzyme activity

Feedback Inhibition also called end product inhibition inhibition of one or more critical enzymes in a pathway regulates entire pathway pacemaker enzyme catalyzes the slowest or rate-limiting reaction in the pathway

each end product regulates its own branch of the pathway isoenzymes – different enzymes that catalyze same reaction each end product regulates the initial pacemaker enzyme Feedback inhibition of a branching pathway with two end products (P and Q). Reaction converting substrate A to intermediate B is catalyzed by isoenzymes, each regulated by a different end product (P or Q).