CHEM 30 B  Dr. R. Rinehart
Chapter 20   ENZYMES

 ENZYMES are biological catalysts; without them, life would be impossible, since the thousands of reactions required to keep even a single cell alive would occur far too slowly to support life. With only a handful of exceptions, enzymes are proteins.

 I. Enzyme characteristics
            A. Globular proteins (soluble enzymes; membrane-bound enzymes have extra hydrophobic segment)
            B. Catalytic efficiency:  accelerate reaction rate by 10² to 10²⁰ times at ordinary temperatures
            C. Specificity for both substrate and reaction catalyzed
                        1. absolute: works on only one substrate;
                                 may be stereospecific, group-specific, linkage-specific
                        2. relative: works on several structurally-related substrates
                        3. reaction specificity minimizes byproduct formation and substrate waste
            D. Catalytic activity can be regulated [see IV. E,F,G below] 

II. Nomenclature and classification
            A. Archaic: e.g., trypsin, chymotrypsin, pepsin, steapsin, amylopsin
            B. Common: add -ase to name of substrate or to combination of substrate name
                         and reaction catalyzed e.g., amylase, lipase, urease, lactate dehydrogenase
            C. E.C. (from the international Enzyme Commission):
                                    Six major classes based on type of reaction catalyzed [1^st #]; 
                                    subclasses based on type of bond involved [2^nd #], cofactors required [3^rd #],
                                     and specific substrate attacked [4^th #]; name also ends in -ase
                                    Each enzyme has a unique EC catalog number
                        1. Oxidoreductases:   e.g., alcohol dehydrogenase, EC 1.1.1.1
                                    catalyze oxidation/reduction (electron transfer) reactions
                        2. Transferases   e.g., hexokinase, EC 2.7.1.1
                                    catalyze group transfer reactions
                        3. Hydrolases:   e.g., chymotrypsin, EC 3.4.21.1
                                    includes all digestive enzymes and many others
                                    catalyze hydrolysis of esters, amides, thioesters, phosphate esters, sulfate esters,
                        4. Lyases   e.g., fumarase  or fumarate hydratase,  EC 4.2.1.2
                                    addition of H₂O, NH₃, etc. to double bonds or the reverse reactions
                        5. Isomerases   e.g., phosphohexose isomerase, EC 5.3.1.9
                                  move a group from one position to another within a molecule or change DßàL
                        6. Ligases  e.g.  tyrosine -- tRNA ligase, EC 6.1.1.1
                                    attach two smaller molecules together using energy from ATP or similar source 

© Ronald W. Rinehart, 2002  Pictures made with MDL IsisDraw®

III. Cofactors ( “activators”, coenzymes and prosthetic groups): 
                    nonprotein components required for catalytic activity
            A. Inorganic: Ca⁺², Mg⁺², Zn⁺², Fe⁺², Cl^-, etc.; often called “activators”
            B. Organic: “coenzymes”; usually derived from vitamins
                the term "prosthetic group" is used to describe coenzymes which are "permanently" bound to their
                 enzyme [e.g., the heme group in cytochromes or FAD in succinate dehydrogenase], while other
                coenzymes such as NAD⁺ are "soluble" and exist in a pool which can be utilized by many 
                different enzyme molecules. 

IV. Enzyme activity
            A. Mechanism [a mechanism is a detailed molecular picture of exactly how a reaction happens]
                        1. Takes place at “active site”
                        2. Enzyme’s 3^o structure is specifically designed to recognize and bind substrate through
                             a combination of forces: electrostatic/ionic, dipolar, H-bonding, dispersion/hydrophobic. 
                        3. Active complex formation:   

    E       +        S        ßà     ES    ßà   ES*       ßà    EP    ßà    E       +       P

enzyme         substrate(s)              complex         transition state              complex            enzyme         product(s)          

            4. Mechanism of catalysis usually involves the side chains of from 2 to 5 amino acids
                            acting as precisely-positioned weak acids and bases with the participation of any
                            cofactors required when the side chains alone can't do the job

B. Activity
                        1. Turnover number
                        2. Rate of substrate consumption (International units) or product formation     

C. Factors affecting rate
            1. Enzyme concentration
            2. Substrate concentration
            3. Temperature
            4. pH

D. Inhibition of enzymes
                        1. Irreversible; e.g. heavy metal or cyanide poisoning
                        2. Reversible
                                    a. Competitive: overcome by increasing [S]; I_c ~ S in structure
                                    b. Noncompetitive: not overcome by increasing [S]; I_n must be removed
                                           useful in feedback inhibition of metabolic pathways           

E. Regulation of enzymes
                        1. Activation of zymogens/proenzymes
                        2. Allosteric modulation: can increase or decrease activity; noncompetitive
                                    can coordinate several pathways via feedback inhibition
                        3. Covalent modification: phosphorylation/dephosphorylation,
                                acetylation/deacetylation, methylation/demethylation, etc.
                        4. Genetic control: induction and repression; alter amount of enzyme itself
                        5. Proteolysis will eventually inactivate all enzymes; for some, this may be programmed.
                        6. Hormones can affect both quantity and specific activity of enzymes via one
                                  or more of the mechanisms listed above. 

V. Medical applications of enzymes
            A. Inborn errors of metabolism
            B. Serum enzyme analysis
            C. Isoenzymes
            D. Therapeutic use of enzymes: e.g., streptokinase for dissolving clots

 © Ronald W. Rinehart, 2002, 2004, 2006