清华大学：《生物化学》课程PPT教学课件（英文版）ENZYMES ARE HIGHLY SPECIFIC

table 8-3 International Classification of enzymes No Class Type of reaction catalyzed Oxidoreductases Transfer of electrons(hydride ions or H atom Transferases Group-transfer reactions Hydrolase Hydrolysis reactions(transfer of functional groups to water) 4 Lyases Addition of groups to double bonds, or format of double bonds by removal of groups Isomerases Transfer of groups within molecules to yield isomeric forms Ligases Formation of c-CC-Sc-0, and C-N bonds by condensation reactions coupled to ATP cleavage Most enzymes catalyze the transfer of electrons, atoms, or functional groups. They are theretore classified, given code numbers, and assigned names according to the type of transfer reactio the group donor, and the group acceptor Lehninger

Lehninger

ENZYMES ARE HIGHLY SPECIFIC Enzymes are highly specific both in the reaction catalyzed and in their choice of reactants, which are called substrates. An enzyme usually cata- lyzes a single chemical reaction or a set of ciosely related reactions. Side reactions leading to the wasteful formation of by-products rarely occur in enzyme-catalyzed reactions, in contrast with uncatalyzed ones. The de gree of specificity for substrate is usually high and sometimes virtually absolute

Let us consider proteolytic enzymes as an example. The reaction catalyzed by these enzymes is the hydrolysis of a peptide bond H O H O N-C—C—N—C-C—+H2O 一N=C-C++H2N-C H Peptide Carboxyl Amino component component Most proteolytic enzymes also catalyze a different but related reaction. namely, the hydrolysis of an ester bond R1-C-0-R2+H2O-=R1 +Ho-R,+H+ Ester Acid Alcohol

H O H O H O T N—C—C一N-C—C-N—C—C H2O N-C-C一NCC+H2N-C H H R H Lysine Lysine arginine arginine Figure 3-21 Trypsin hydrolyzes polypeptide on the car boxyl side of arginine and lysine residues

Hydrolysis site H N一C—C+N-C-C H Lysine or argInine Hydrolysis site H O H N—C—C+N—C-C H H B Arginine Glycine Figure 8-1 Comparison of the specificities of (A) trypsin and (B)thrombin, Trypsin cleaves on the carboxyl side of argi nine and lysine residues. Thrombin cleaves Arg-Gly bonds in particular sequences only

THE CATALYTIC ACTIVITIES OF MANY ENZYMES ARE REGULATED The enzvme that catalyzes the first step in a biosynthetic pathway is usul- lly inhibited by the ult imate product( Figure 8-2). The biosynthesis of isoleucine in bacteria illustrates this type of control, which is called feed- back inhibition. Threonine is converted into isoleucine in five steps, the first of which is catalyzed by threonine deaminase. This enzyme is inhib ited when the concentration of isoleucine reaches a sufficiently high level Ways of Enzyme Activity Regulations 1. Feed-back Inhibition 2. Regulatory proteins 3. Covalent modification 4. Proteolytic Activation

1. Feed-back Inhibition 2. Regulatory Proteins 3. Covalent Modification 4. Proteolytic Activation Ways of Enzyme Activity Regulations

1. Feed-back Inhibition Enzyme hibited by Z C D Z End product Figure 8-2 Feedback inhibition of the first enzyme in a pathway by reversible binding of the final product

1. Feed-back Inhibition

Threonine→→→→> Isoleucine Threonine deaminase Isoleucine inhibits by binding to the enzyme at a regulatory site, which is distinct from the catalytic site. This inhibition is mediated by an allosteric interaction which is rapidly reversible. When the level of isoleucine drops sufficiently, threonine deaminase becomes active again, and consequently isoleucine is synthesized once more

Threonine → → → → → Isoleucine Threonine deaminase

coo HaN H-C-OH E B COO HN-C-H H--C-CH, L-Isoleucine igure 8-25 Feedback inhibition. The conversion of L-threonine to L-isoleucine is catalyzed by a sequence of tive enzymes (E to E.). Threonine dehydratase (E )is specifically inhibited by L-isoleucine, the end product of the sequence, but not by any of the four intermediates (A to D), Feedback inhibition is indicated by the dashed feedback line and the o symbol at the threonine dehy dratase reaction arrow, a device that is used throughout this book Lehninger

Lehninger

Binding of a bstrate or signal molecule Transmitted conformational change igure 2-57 Fi Schematic diagram of an allosteric interaction in a protein. The binding of a small molecule or macromolecule to a site in the protein leads to con- formational changes that are propa gated to distant sites