Harpers

50 / CHAPTER 7132 2Enzyme site14SubstrateFigure 7–1. Planar representation of the “threepointattachment” of a substrate to the active site of anenzyme. Although atoms 1 and 4 are identical, onceatoms 2 and 3 are bound to their complementary siteson the enzyme, only atom 1 can bind. Once bound toan enzyme, apparently identical atoms thus may be distinguishable,permitting a stereospecific chemicalchange.2. Transferases catalyze transfer of groups such asmethyl or glycosyl groups from a donor moleculeto an acceptor molecule.3. Hydrolases catalyze the hydrolytic cleavage ofC⎯ C, C⎯O, C⎯N, P⎯ O, and certain otherbonds, including acid anhydride bonds.4. Lyases catalyze cleavage of C⎯ C, C⎯ O, C⎯N,and other bonds by elimination, leaving doublebonds, and also add groups to double bonds.5. Isomerases catalyze geometric or structuralchanges within a single molecule.6. Ligases catalyze the joining together of two molecules,coupled to the hydrolysis of a pyrophosphorylgroup in ATP or a similar nucleoside triphosphate.Despite the many advantages of the IUB system,texts tend to refer to most enzymes by their older andshorter, albeit sometimes ambiguous names.PROSTHETIC GROUPS, COFACTORS,& COENZYMES PLAY IMPORTANTROLES IN CATALYSISMany enzymes contain small nonprotein molecules andmetal ions that participate directly in substrate bindingor catalysis. Termed prosthetic groups, cofactors, andcoenzymes, these extend the repertoire of catalytic capabilitiesbeyond those afforded by the limited numberof functional groups present on the aminoacyl sidechains of peptides.3Prosthetic Groups Are Tightly IntegratedInto an Enzyme’s StructureProsthetic groups are distinguished by their tight, stableincorporation into a protein’s structure by covalent ornoncovalent forces. Examples include pyridoxal phosphate,flavin mononucleotide (FMN), flavin dinucleotide(FAD), thiamin pyrophosphate, biotin, andthe metal ions of Co, Cu, Mg, Mn, Se, and Zn. Metalsare the most common prosthetic groups. The roughlyone-third of all enzymes that contain tightly boundmetal ions are termed metalloenzymes. Metal ions thatparticipate in redox reactions generally are complexedto prosthetic groups such as heme (Chapter 6) or ironsulfurclusters (Chapter 12). Metals also may facilitatethe binding and orientation of substrates, the formationof covalent bonds with reaction intermediates (Co 2+ incoenzyme B 12 ), or interaction with substrates to renderthem more electrophilic (electron-poor) or nucleophilic(electron-rich).Cofactors Associate Reversibly WithEnzymes or SubstratesCofactors serve functions similar to those of prostheticgroups but bind in a transient, dissociable manner eitherto the enzyme or to a substrate such as ATP. Unlikethe stably associated prosthetic groups, cofactorstherefore must be present in the medium surroundingthe enzyme for catalysis to occur. The most commoncofactors also are metal ions. Enzymes that require ametal ion cofactor are termed metal-activated enzymesto distinguish them from the metalloenzymes forwhich metal ions serve as prosthetic groups.Coenzymes Serve as Substrate ShuttlesCoenzymes serve as recyclable shuttles—or grouptransfer reagents—that transport many substrates fromtheir point of generation to their point of utilization.Association with the coenzyme also stabilizes substratessuch as hydrogen atoms or hydride ions that are unstablein the aqueous environment of the cell. Otherchemical moieties transported by coenzymes includemethyl groups (folates), acyl groups (coenzyme A), andoligosaccharides (dolichol).Many Coenzymes, Cofactors, & ProstheticGroups Are Derivatives of B VitaminsThe water-soluble B vitamins supply important componentsof numerous coenzymes. Many coenzymes contain,in addition, the adenine, ribose, and phosphorylmoieties of AMP or ADP (Figure 7–2). Nicotinamideand riboflavin are components of the redox coenzymes