Chapter 23:

Catalysis

Chapter 23
Recommended Problems: all of the in-chapter problems and 30-33, 35,
36, 38, 40, 41-44, 46

Importance of Catalysis
Nitrogen fixation and Fritz Haber
Nitrogen is abundant but unreactive
Converting N2(g) to a useable form
(NH3) is a very high energy process
Fritz Haber discovered the use of an
osmium catalyst can greatly reduce the
energy required
1/2 to 1/3 of the world food supply
comes from the Haber process
His other legacy:
Nobel Prize 1919
Chemical Warfare in World War I
Indicted as a war criminal in 1920

An Acid-Catalyzed Reaction
An acid catalyst increases the rate of a reaction by donating a proton.

How an Acid Catalyzes the

First Slow Step
A catalyst must increase the rate of a slow step.

The catalyst increases the electrophilicity of the carbonyl carbon

(makes it more susceptible to nucleophilic addition).

How an Acid Catalyzes the

Second Slow Step

The catalyst decreases the basicity of the leaving group

(increases its propensity to leave).

Comparing Specific-Acid Catalysis with

General-Acid Catalysis

Specific-Acid and General-Acid Catalysis

A specific-acid catalyst must be a strong acid.

A general-acid catalyst can be a weaker acid.

Specific-Base Catalysis
A base catalyst increases the rate of a reaction by removing a proton.

In specific-base catalysis, the proton is removed from the reactant

before the slow step.

General-Base Catalysis

In general-base catalysis, the proton is removed from the reactant

during the slow step.

Nucleophilic Catalysis

Imidazole is a better nucleophile than water.

An acyl imidazole hydrolyzes more rapidly than an ester
because imidazole is a better leaving group than the phenolate ion.

The Carboxyl Group is a Catalyst

An Intramolecular General-Base Catalyst

An Intramolecular Nucleophilic Catalyst

An Enzyme Binds its Substrate at

its Active Site

The reactant is called a substrate.

Lock and Key versus Induced Fit

Induced Fit

Carboxypeptidase A
(an exopeptidase)

Endopeptidases
The binding pocket at the active site of serine proteases
determines the substrate specificity.

Site-Specific Mutagenesis
(a technique that replaces one amino acid with another)

When Asp102 of chymotrypsin is replaced by Asn102, the catalysis drops to 0.05%.

Therefore, Asp102 must be involved in the catalytic process.

Lysozyme
(an enzyme that destroys bacterial cell walls)

The amino acids

at the active site
of lysozyme are
involved in binding
the substrate.

A pH-Activity Profile

This group is
catalytically active
in its basic form.

This group is
catalytically active
in its acidic form.

A Pyridine Nucleotide Coenzyme is Needed

for Many Redox Reactions

NAD+ and NADP+ are oxidizing agents.

NADH and NADPH are reducing agents.

The Mechanism

Most Enzyme-Catalyzed Reactions are

Highly Selective

The oxidizing enzyme can distinguish between the two hydrogens of ethanol.
Only Ha is removed.

Most Enzyme-Catalyzed Reactions are

Highly Selective

The reducing enzyme can distinguish between the two hydrogens of NADH.
Only Ha is transferred.

FAD is an Oxidizing Agent

FAD = flavin adenine dinucleotide

The Mechanism for

Succinate Dehydrogenase

The Mechanism for

D- or L-Amino Oxidase

The Pyruvate Dehydrogenase Complex

The conversion of pyruvate to acetyl-CoA requires

five coenzymes: TPP, lipoate, coenzyme A, FAD, and NAD+.

Part Two of the Mechanism

Part one of the mechanism is the reaction of the TPP ylide with
pyruvate to form the same enamine that is formed from the
reaction of the TPP ylide with pyruvate by pyruvate carboxylase.
Lipoate is attached to its enzyme by forming an amide with a lysine side chain.

Part Three of the Mechanism

Coenzyme A

Mechanism for Carboxylation

The Pyruvate Dehydrogenase Complex

The conversion of pyruvate to acetyl-CoA requires

five coenzymes: TPP, lipoate, coenzyme A, FAD, and NAD+.

Part Two of the Mechanism

Part one of the mechanism is the reaction of the TPP ylide with
pyruvate to form the same enamine that is formed from the
reaction of the TPP ylide with pyruvate by pyruvate carboxylase.
Lipoate is attached to its enzyme by forming an amide with a lysine side chain.

Part Three of the Mechanism

Coenzyme A

Mechanism for Carboxylation

All mechanisms with PLP begin with the transimination reaction. PLP
forms an imine with the amino acid.

The Mechanism for Decarboxylation

The Mechanism for Racemization

The Mechanism for Transamination

(Part 1)

The Mechanism for Transamination

(Part 2)

Coenzyme B12

The Mechanism for a

Reaction that Requires B12

Attack of a Carboxylate Ion

on the -Phosphorus

Attack of a Carboxylate Ion

on the -Phosphorus

Pyrophosphate is Hydrolyzed to Phosphate

Hydrolyzing pyrophosphate to phosphate ensures the irreversibility of the reaction.

The Reaction of a Nucleophile with

ATP is a Highly Exergonic Reaction

The Four Stages of Catabolism

The reactions in the first stage
are hydrolysis reactions.

The products of the first stage are

converted to acetyl-CoA or to
citric acid cycle intermediates.

The acetyl-CoA formed in the

second sage enters the
citric acid cycle.
ATP is synthesized in the
fourth stage.

Catabolism of Carbohydrates

In the first stage of catabolism, an enzyme-catalyzed reaction

hydrolyzes the carbohydrate to molecules of glucose.

glycolysis

An Enediol Rearrangement Converts Dihydroxyacetone

Phosphate to Glyceraldehyde-3-Phosphate

Oxidizing Glyeraldehyde-3-phosphate to
1,3-Bisphosphoglycerate

NAD+ catalyzes this oxidation reaction.

(The mechanism is shown on page 1138.)

A Phosphate is Transferred to ADP

to Form ATP

An Isomerization Reaction

An E1cb Reaction Converts

2-Phosphoglycerate to Phosphoenolpyruvate

A Phosphate is Transferred to ADP

to Form ATP

Coupled Reactions

An exergonic reaction drives the reaction that precedes it.

glycolysis

Oxidizing Glyeraldehyde-3-phosphate to
1,3-Bisphosphoglycerate

NAD+ catalyzes this oxidation reaction.

(The mechanism is shown on page 1138.)

A Phosphate is Transferred to ADP

to Form ATP

An Isomerization Reaction

the citric acid cycle

An Aldol Addition Followed by

Hydrolysis

An E2 Reaction Followed by
the Conjugate Addition of Water

Oxidation, Decarboxylation,Tautomerization

The Overall Reaction is the

Transfer of an Acyl Group to CoASH

The mechanism for this reaction is the same as that for the
pyruvate dehydrogenase complex (pp. 11461147).

Succinyl-CoA to Succinate

A nucleophilic additionelimination reaction

followed by transfer of a phosphate group to GDP.

the citric acid cycle

glycolysis and
gluconeogeneis

The Mechanism for One of the

Irreversible Reactions in Gluconeogenesis

The Five-Carbon Compound Actually Used for

Biosynthesis is Isopentenyl Pyrophosphate

Conversion of Isopentenyl Pyrophosphate

to Dimethylallyl Pyrophosphate

The biosynthesis of a terpene always starts

with a dimethylallyl pyrophosphate.

Propose a mechanism for the last step

Press A when you have begun

Press B when you are confident in
your answer

Conversion of Isopentenyl Pyrophosphate

to Dimethylallyl Pyrophosphate

The biosynthesis of a terpene always starts

with a dimethylallyl pyrophosphate.

Geranyl = 10 carbons

The Biosynthesis of
Some Monoterpenes

Farnesyl = 15 carbons

Squalene is a Triterpene

Squalene is the precursor of cholesterol.

Cholesterol is the precursor of all the other steroid hormones.

Step-Growth Polymer
(Dacron)

Step-growth polymers (also called condensation polymers), are made by

combining two molecules while removing a small molecule.

Alkenes Used in
Radical Polymerization

Radical Initiators