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.

PowerPoint-type presentations on enzymes and vitamins
by Warren Gallagher at the University of Wisconsin, Eau Claire
Enzyme tutorials using Chime and many other plugins by Duane Sears at UC Santa Barbara 
or and select the enzyme tab near the top
-- and as usual, the
Netscape 4.7x version of Chime works better here.

Enzyme kinetics by Clarke Earley at Kent State University Stark Campus, OH
Some students didn’t like this one too much!
If this URL doesn’t work, try and follow the links

Reactions and Enzymes by M. J. Farabee  at Estrella Mountain CC, Maricopa Cty, AZ
            Not too long, nice pictures, clear and concise; part of an online biology textbook

Enzymes  from Kimball’s Biology Pages by John Kimball
Also pretty good

Enzyme Biochemistry from MIT Biology Hypertextbook
Also short on pictures, although other chapters in the book have lots of them.
Might be a bit heavy for your tastes.


 I. Enzyme characteristics
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
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 [1st #]; 
subclasses based on type of bond involved [2nd #], cofactors required [3rd #],
                                     and specific substrate attacked [4th #]; name also ends in -ase
                                    Each enzyme has a unique EC catalog number
1. Oxidoreductases:   e.g., alcohol dehydrogenase, EC
                                    catalyze oxidation/reduction (electron transfer) reactions
                        2. Transferases   e.g., hexokinase, EC
catalyze group transfer reactions
                        3. Hydrolases:   e.g., chymotrypsin, EC
                                    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
                                    addition of H2O, NH3, etc. to double bonds or the reverse reactions
5. Isomerases   e.g., phosphohexose isomerase, EC
                                  move a group from one position to another within a molecule or change DßàL
6. Ligases  e.g.  tyrosine -- tRNA ligase, EC
                                    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 3o 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

See an illustrated discussion of an enzyme mechanism by Mark Bishop of MPC
After reading that, you will better appreciate the animated serine protease mechanism 
from Gordon Rule's course at Carnegie Mellon University
we'll look at all this in greater depth on Wednesday

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]; Ic ~ S in structure
b. Noncompetitive: not overcome by increasing [S]; In 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

See how an understanding of enzyme structure and mechanisms led to the development of an inhibitor of the HIV protease at 

 © Ronald W. Rinehart, 2002, 2004, 2006