Ch. 9: Enzymatic Catalysis (WIP)

4 ways enzymes differ from regular catalysts

higher rxn rates; milder rxn conditions; greater rxn specificity; capacity for regulation

allosteric

relating to a change in shape & activity of a protein via a molecule bonding to a site other than the active site

diffusion-limited reaction rate

only limited by how fast the substrate gets to it

7 classes of enzyme

oxidoreductase; transferase; hydrolase; lyase; isomerase; ligase; translocase

3 ways enzymes are regulated

allosteric control; covalent modification; enzyme synthesis

oxidoreductase purpose

electron transfer

6 categories of oxidoreductases

dehydrogenase; oxidase; peroxidase; reductase; oxygenase; hydroxylase

transferase purpose

transfer fxnl grps between molecules

transferase examples

kinase; transminase; methylase; transketolase; sulfotransferase; glycosylase; manyn more

oxidoreductase specific example

lactate dehydrogenase; oxidizes lactate into pyruvate/reduces pyruvate into lactate

tranferase specific example

alanine transaminase; transfers amino group from alanine to alpha-ketoglutarate, creating pyruvate & L-glutamate

hydrolase purpose

hydrolysis rxns

hydrolase specific example

pyrophosphatase; separates pyrophosphate into 2 phosphate

hydrolase categories

esterase; lipase; glycosidase; peptidase; nucleosidase; many more

lyase purpose

group elimination to form a double bond or new ring structure (not by hydrolysis or oxidation!)

lyase example

pyruvate decarboxylase; turns pyruvate into acetaldehyde & CO2

lyase categories

synthase; decarboxylase; dehydratase; aldolase; cyclase

isomerase example

alanine racemase converts alanine between L and D configurations

3 isomerase types

racemase; epimerase; mutase

isomerase

catalyze changes in molecular configuration between isomers

ligase

catalyze bond formation coupled with ATP hydrolysis

3 ligase subcategories

synthase; synthetase; carboxylase

difference between synthase & synthetase

synthetases use ATP, synthases do not

translocase

catalyze movement of molecules across/within membranes

translocase subcategory

ATPase

translocase example

carnitine/acylcarnitine trasnslocase

ligase example

glutamine synthetase; turns glutamate into glutamine

active site

an indentation or cleft on an enzyme where the substrate is bound; has geometric and electronic complementarity

induced fit

conformation change of an enzyme after substrate binding

primary means of enzyme catalysis

binding energy released with substrate distortion into the transition state is a major contributor to lowering activation energy

transition state

the point of highest free energy in a reaction process

what energetic property of rxns do enxymes not change

∆G; the overall change in free energy of the rxn

example of a highly permissive enzyme

digestive enzymes

4 catalytic mechanisms other than binding energy

metal ion catalysis; acid-base catalysis; covalent catalysis; proximity & orientation effects. many of these involve enzymatic cofactors

what form of the substrate do enzymes preferentially bind?

the transition state, for which they have the highest complementarity

how do enzyme inhibitors relate to transition states?

many inhibtors are transition state analogs

how long do transition states last?

10^-13 to 10^-14 s

rxn types in which active site side chains (usually ionizable) are most effective

acid-base; transient covalent bond formation; charge-charge intrxns

rxn types in which a cofactor is necessary sometimes

redox; group transfer

cofactor

an ion or small molecule that helps drive catalysis

2 main classes of cofactors

essential metal ions; coenzymes

essential metal ion categories

activator ions (loose); metalloenzyme ions (tight)

coenzyme categories

cosubstrates (loose); prosthetic grps (tight)

how common are metal ion cofactors?

used in roughly 1/3 of all enzymes

3 ways metal ions participate in catalysis

binding to substrates & orienting them; mediating redox rxns by reversibly changing oxidation state; electrostatically stabilizing or shielding negative charges

metal ions as cofactors

often play a structural (indirect) role; may be necessary or just rate-increasing

4 typical metal ion cofactors

Na+; K+; Ca2+; Mg2+. (electrolytes)

metalloenzymes

tightly bound in active site; generally necessary for catalysis

5 typical metalloenzyme ions

Fe2+; Zn2+; Cu2+; Co2+; Mo2+. (transition metals)

metal ion cofactor examples

Zn2+ in carbonic anhydrase; iron-sulfur clusters; Fe in heme grps

cosubstrate

fxn as co-reactants, but are regenerated & reused

carbonic anhydrase purpose

moderates blood pH

cosubstrate example

nicotinamide adenine dinucleotide (NAD+); from niacin, vitamin B3

prosthetic groups

remain bonded to enzyme (covalent or strong non-covalent)

prosthetic group example

flavin adenine dinucleotide (FAD); from riboflavin, vitamin B2

zymogen

aka proenzyme; converted to an active enzyme by cleavage at 1 or more peptide bonds. eg hydrolysis or configurational change to reveal active site

zymogen example

pepsinogen is converted to pepsin by HCL in the stomach