Proteins are the workhorses in living systems. Their many roles include providing structure, catalyzing nearly all the reactions that take place in a living cell, transporting and storing materials, and controlling and defending living systems. Like carbohydrates, proteins are polymers, but unlike the polysaccharides, proteins are able to assume a much wider range of 3-dimensional structures and a functions. In this unit we will focus on one the of the most important functions of proteins; that of biological catalysts (enzymes).

2
Amino Acids
α-Amino acids are the building blocks (monomers) for polypeptides and proteins.
•
Every amino acid contains,
•
A carboxylic acid group
•
An amino group
•
A side chain (R)

3
Amino Acids
Back in Unit 7 we saw that carboxylic acids behave as acids when dissolved in water.

4
Question (Clickers) (Unit 7)
At pH 7, which will be the predominant species?
A) Carboxylic acid
B) Carboxylate ion H
2
O acid base pK a
≈ 5
O
CH
3
C base
O + H
3
O
+ acid carboxylic acid carboxylate ion

5
Carboxylic Acids & Phenols as Weak Acids
(Unit 7)
•
At pH 7, the carboxylate ion of carboxylic acids predominate
•
At pH = pK a
O O
•
At
CH
3
C pH < pK a acid
OH + H
2
O base
•
At pH > pK a pK a
≈ 5
CH
3
C base pH = 7
O + H
3
O
+ acid
O
CH
3
C acid
OH =
O
CH
3
C base
O
O
CH
3
C acid
OH >
O
CH
3
C base
O
O
CH
3
C acid
OH
<
O
CH
3
C base
O

6
Amino Acids
Back in Unit 7 we also saw that amines behave as bases when dissolved in water.

7
Amines as Weak Bases (Unit 7)
Like ammonia, 1 °, 2° and 3°, act as Brønsted-Lowry bases.
CH
3
N H ( aq )
H methanamine
(base)
+ H
2
O ( l )
H
CH
3
N H ( aq )
H methylammonium ion
(acid)
+ OH
-
( aq )

8
Amines as Weak Bases (Unit 7)
The conjugate acids are called ammonium ions
•
When placed in water, these ammonium ions will behave like acids.
H pK a
- 10
CH
3
N H ( aq ) + H
2
O ( l ) CH
3
N H ( aq ) + H
3
O
+
( aq )
H methylammonium ion
(acid)
H methanamine
(base)

9
Amino Acids
At pH 7, amino acids are in their zwitterionic form.
•
There is no pH value at which there are no charges on an amino acids.
•
However, there is a pH value at which the net charge is zero.
•
This pH value is called the isoelectric point .
Net charge
+1
0
-1

10
Amino Acids
There are 20 different sidechains for the amino acids that are used to build proteins.
•
These are classified according to their physical properties as
•
Non-polar
•
Polar acidic (negatively charged at pH 7)
•
Polar basic (positively charged at pH 7)
•
Polar neutral (polar, but not charged at pH 7)

11
Non polar sidechains
•
Most of these sidechains are hydrocarbons
Amino Acids

12
Polar acidic sidechains
•
Sidechains contain carboxylic acids
•
Negatively charged at pH 7
Amino Acids

13
Amino Acids
Polar basic sidechains
•
Sidechains contain amines
•
Positively charged at pH 7

14
Amino Acids
Polar neutral sidechains
•
Sidechains contain polar groups that are capable of hydrogen bonding
• alcohols
• phenols
• amides
•
Uncharged at pH 7

15
Amino Acids
For all of the amino acids, except one (glycine), the α-carbon is chiral.
•
Fisher projection of the amino acids alanine:
•
With few exceptions, only the L -amino acids are used to make proteins.

16
Peptides, Proteins, and pH
Amino acids are joined together to form polymers of amino acids called oligopeptides (2-10 amino acids) and polypeptides (more than 10 amino acids).
•
Collectively, oligopeptides and polypeptides are called peptides .
•
The amino acids are joind together by an amide bond called a peptide bond , which is analogous to the glycosidic bond found in oligosaccharides and polysaccharides.
•
Back in Unit 7 we saw how carboxylic acids can react with ammonia and amines to form amides.

17
Amides (Unit 7)
•
When a carboxylic acid reacts with an amine it also produces and ammonium salt
•
If the ammonium salt is then heated, an amide is produced.

18
Amides (Unit 7)
Amides are important in biochemistry.
•
For example, amino acids are connected together to form proteins using amide groups.
amino acid

19
Peptides, Proteins, and pH
Peptide bond formation
H
C
H
3
N
H
C
O
O
H + H
H
N
O
H
C
CH
2
C
O
Peptide Bond
H H O
H
C
H
3
N
H
C
O
N
C
CH
2
C
O
+ H O H
Dipeptide

20
Peptides, Proteins, and pH
•
The amide bond that connects the amino acids together in a peptide is called a peptide bond .
•
Proteins are long polypeptide chains, usually with 50 or more amino acids, which fold into a well defined structure.
The protein ubiquitin

21
Peptides, Proteins, and pH
Proteins are sensitive to the pH because they contain numberous acid and base groups
•
The pH affects the charge on a proteins, which in turn, can have a marked effect on a protein’s structure and function.

22
Peptides, Proteins, and pH
Net Charge Example
•
The charges on the tripeptide
Lys-Ser-Asn as a function of pH .
+2
0
-2

23
Peptides, Proteins, and pH
Net Charge Example
•
The charges on the tripeptide
Lys-Lys-Ala as a function of pH .
+3
+2
-1

24
Peptides, Proteins, and pH
Amino acids with acid or base side chains have additional charge groups:
• e.g. Glutamic acid is an acid amino acid
•
At pH ’s below the isoionic point ( pI ) the charge is positive
•
At pH ’s above the isoionic point ( pI ), the charge is negative
H O
H
H
3
N C
O
C OH
OH
–
H
H
3
N C
O
C O
OH
–
H
H
3
N C
O
C O
OH
–
H
+
H
2
N C C O
H
+ H
+
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
C O
C OH
C OH
C O
O
O
O
O
9 < pH pH < 2
2 < pH < 4.4
4.4 < pH < 9
-2
+1
0 pI = 3.2
-1

Peptides, Proteins, and pH
25
Amino acids with acid or base side chains have additional charge groups:
• e.g. Lysine is a basic amino acid
•
At pH ’s below the isoionic point ( pI ) the charge is positive
•
At pH ’s above the isoionic point ( pI ), the charge is negative
H O
H O
OH
–
H O
OH
–
H O
OH
–
H
3
N C C OH H
3
N C C O H
2
N C C O H
2
N C C O
H
+ H
+ H
+
CH
2
CH
2
CH
2 CH
2
CH
2 CH
2
CH
2
CH
2
CH
2 CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
NH
2 NH
3
NH
3
NH
3 pH < 2
+2
2 < pH < 9
+1
9 < pH < 10.3
0 pI = 9.7
10.3 < pH
-1

26
Peptides, Proteins, and pH
We are going to simplify the determination of charge as a function of pH by looking only at pH 1, pH 7, and pH 14:
Charges at different pH values
Acids
A
Bases
B
Include:

-COOH
Asp sidechain
Glu sidechain
Includes:

-NH
2
His sidechain
Lys sidechain
Arg sidechain pH 1 pH 7 pH 14
0 -1 -1
+1 +1 0

27
Question
At pH 7 , which of the following amino acids have a net positive charge, which have a net negative charge, and which are neutral?
Lysine
Phenylalanine
Leucine

28
Question
Lysine
B
H
2
N
H
CH
2
CH
2
CH
2
O
C C
CH
2
NH
2
B
A Charges at different pH values
OH
A 
-COOH
B 
-NH
2
B
Lys sidechain
Net pH 1 pH 7 pH 14
0 -1
+1 +1
+1 +1
+2 +1
-1
0
0
-1

29
Question
Draw the structure of the following tripeptide Glu-Asp-Phe at pH 1 and high pH 14 .

30
Question
Draw the structure of the following tripeptide Glu-Asp-Phe at pH 1 and high pH 14 .
Draw the backbone
H
H
2
N C
R
O
C N
H
H
C
R
O
C N
H
H
C
R
O
C OH

31
Question
Draw the structure of the following tripeptide Glu-Asp-Phe at pH 1 and high pH 14 .
Add the sidechains and identify the acids ( A ) and bases ( B )
B
H
H
2
N C
CH
2
O
C
CH
2
A
C
O OH
Glu t a m ic Acid
(Glu )
H O
N C
H CH
2
A
O
C
OH
C N
H
H
C
CH
2
O
C
A
OH
Aspartic acid
(Asp)
Phenylalanine
(Phe)

32
Question
Draw the structure of the following tripeptide Glu-Asp-Phe at pH 1 and high pH 14 .
At pH 1 , Acids ( A ) are 0 and Bases ( B ) are +1
B
H
H
3
N C
CH
2
O
C
CH
2
A
C
O OH
Glu t a m ic Acid
(Glu )
N
H
C
H CH
2
A
O
C
OH
O
C N
H
H
C
CH
2
O
C
A
OH
Net Charge = +1 at pH 1
Aspartic acid
(Asp)
Phenylalanine
(Phe)

33
Question
Draw the structure of the following tripeptide Glu-Asp-Phe at pH 1 and high pH 14 .
At pH 14 , Acids ( A ) are -1 and Bases ( B ) are 0
B
H
H
2
N C
CH
2
O
C
CH
2
A
C
O O
Glu t a m ic Acid
(Glu )
N
H
C
H CH
2
A
O
C
O
O
C N
H
H
C
CH
2
O
C
A
O
Net Charge = -3 at pH 14
Aspartic acid
(Asp)
Phenylalanine
(Phe)

34
Protein Structure
Proteins are polypeptides that fold to adopt a well-defined, three-dimensional structure.
There two general classifications of proteins
•
Fibrous proteins exist as long fibers that are usually tough and insoluble in water; examples include
• collagen (skin and bones)
•
Keratin (hair)
•
Globular proteins are spherical, highly folded, and usually soluble in water; examples include
• enzymes
• antibodies
• transport proteins like hemoglobin and myoglobin

35
Protein Structure
Fibrous versus globular

36
Protein Structure
Proteins display up to four levels of structure
•
Primary structure
•
This is the amino acid sequence, which is unique for each protein
•
This defines the covalent structure of a protein
•
Secondary structure
•
Regular, periodic structures, that involve hydrogen bonding between the backbone amides
H O H O
C hydrogen b onds between amides
N C
H R
O
C N
H
H
C
R
N
H
O
C
C
R
C
H
N C
H R
N
H
O
C

37
Protein Structure
Proteins display up to four levels of structure
•
Tertiary structure
•
The 3-dimensional fold of the the polypeptide in which the backbone twists and turns its way through the folded structure of the protein.
•
It involves interactions between the sidechains of the the amino acids and is highly influenced by the amino acid sequence.
The protein ubiquitin

38
Protein Structure
Primary Structure
• A protein’s amino acid sequence is referred to as its primary structure .
•
Every protein has a unique primary structure that is determined by the gene for that protein.
•
The primary structure defines the covalent structure of a protein.

Protein Structure
Primary Structure
Glycine
Gly
Alanine
Ala
Serine
Ser
Aspartic Acid
Asp
39
O O
OH C
C-Terminus
H
C
H
3
N C
H
N-Terminus
O
H
N
H
C
CH
2
O
C
N
H
CH
3
C
C
H
O
Phenylalanine
Phe
H
N
H
C
O
C
N
CH
2
HC CH
3
CH
3
H
CH
2
C
C
H
O
H
N
Leucine
Leu
H
C
CH
2
CH
2
CH
2
CH
2
NH
3
Lysine
Lys
O
C
N
H
CH
2
C
C
H
O
H
N
H
C
O
C
O
CH
2
CH
2
C
NH
2
O
Gluctamine
Gln

Protein Structure
40
Primary Structure
O O
OH C
C-Terminus
H
C
H
3
N C
H
N-Terminus
O
H
N
H
C
CH
2
O
C
N
H
CH
3
C
C
H
O
H
N
H
C
O
C
N
CH
2
HC CH
3
H
CH
3
CH
2
C
C
H
O
H
N
H
C
CH
2
CH
2
CH
2
CH
2
NH
3
O
C
N
H
CH
2
C
C
H
O
H
N
H
C
O
C
O
CH
2
CH
2
C
NH
2
O
Glycylphenylalanylalanylleucylseryllysylaspartylglutamine
H
2
H-Gly-Phe-Ala-Leu-Ser-Lys-Asp-Gln-COOH
Gly-Phe-Ala-Leu-Ser-Lys-Asp-Gln
GFALSKDQ

41
Protein Structure
Primary structure
•
The Central Dogma
• DNA → mRNA → Polypeptide
The genetic code is used to match up the
DNA/mRNA sequence to the sequence of amino acids in a protein
All living organisms use the same code

42
Protein Structure
•
The functional diversity of proteins results from the large number of possible proteins that can be built using the 20 different amino acids
•
Question : How much mass would it take to construct one molecule each of all of the possible polypeptides containing 100 amino acids residues?
o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o
•
View the polypeptides as beads on a string, with one of 20 possible types of beads at each position.

43
Protein Structure
The Earth weighs 6.0 x 10
27 take?
g, how many Earths would it

44
Protein Structure
The Sun weighs 2.0 x 10
33 g , how many Suns would it take?

45
Protein Structure
The Milky Way galaxy weighs 1.2 x 10
45 times the mass of the sun
(1.2 x 10 45 suns )(2.0 x 10 33 g/sun) = 2.4 x 10 78 g
How may galaxies would it take?

46
Protein Structure
The Coma galaxy cluster contains several thousand galaxies, how many ...?

47
Protein Structure
Number of polypeptides (20 100 )
Avg. Mass of each polypeptide
Total mass needed
Number of Earths
Number of Suns
Number of Galaxies
1.26 x 10
130
1.83 x 10
-22 g
2.32
x 10
108 g
3.9 x 10
80
1.2 x 10
75
9.7 x 10
29

48
Protein Structure
Secondary structure
•
The polypeptide backbone can take on regular shapes that allow the backbone amides to hydrogen bond to one another.
•
The primary forms of secondary structure include
• α-helix
• β-sheet

49
Protein Structure
Secondary structure
α-Helix

50
Protein Structure
Secondary Structure
β-Sheet

51
Protein Secondary Structure
Secondary Structure
Antiparallel β-Sheet

52
Protein Structure
Secondary Structure
Parallel β-Sheet

53
Protein Structure
Tertiary Structure
•
The different elements of secondary structure come together to create the overall 3-dimensional structure of the the protein
•
The structure is stabilized primarily by sidechain interactions and is highly influenced by the amino acid sequence (primary structure).
The protein ubiquitin

54
Protein Structure
Tertiary Structure
•
This is usually the native , or biologically active, form of the protein.
•
When placed in water, the polypeptide folds to maximize the number of nonpolar (hydrophobic) residues that are buried on the inside away from exposure to water.
The protein ubiquitin

Tertiary Structure
Protein Structure
55
Explore the tertiary structure and the secondary structure of the protein ubiqu itin
The protein ubiquitin

56
Protein Structure
Tertiary Structure
•
The tertiary structure is stabilized by the same noncovalent interactions that we looked at in determining boiling points and solubilites
•
Charge/Charge interactions (Salt bridges)
•
Ion/Dipole interactions
•
Dipole/Dipole interactions
•
Hydrogen bonding
•
Hydrophobic interactions (nonpolor/water)
•
There is one covalent interactions that stabilizes the tertiary structure of some proteins.
•
Disufide bond

57
Protein Structure
Tertiary Structure
•
The interactions that stabilize the tertiary structure.

58
Protein Structure
Quaternary Structure
•
Some proteins contain multiple polypeptides
•
Each peptide is called a subunit
•
The polypeptides are held together by the same types of interactions that stabilize the tertiary structure.
Explore the quaternary structure of the protein ubiquit in

59
Protein Denaturation
Because the secondary, tertiary and quaternary structures of proteins are stabilized by weak, non-covalent interactions, these structures are easily disrupted by agents that disrupt theses interactions, including:
•
Changes in temperature
•
Changes in pH
•
Mechanical stress (agitation)
•
Soaps and detergents
These agents typically cause the protein to unfold
•
Only the primary structure remains
•
The protein loses it function
The process is called protein denaturation .

60
Protein Denaturation
Christain Anfinsen won a Nobel Prize for showing that protein denaturation can be reversed.
•
The experiment demonstrated that the information necessary to obtain the correctly folded protein structure is contained within the protein’s amino acid sequence (primary structure).
Active
Protein
Inactive
Protein

61
Enzymes
Nearly every reaction that takes place in a living cell has an enzyme associated with it.
•
Enzymes are biological catalysts
•
Most enzymes are proteins
Many human diseases involve enzymes misbehaving
•
Many treatments for diseases involve drugs that target enzymes.

62
Enzymes
The common names for enzymes often describe the substrate (reactant) for the reaction and a description of the reaction that is being carried out on that substrate.
•
The names usually end with -ase .
•
Example: alcohol dehydrogenase alcohol
NAD
+ NADH + H
+
CH
3
CH ethanol
2
OH alcohol dehydrogenase enzyme aldehyde
O
CH
3
C H ethanal
(acetaldehyde)

Question (Clicker)
63
What class of reaction is the alcohol dehydrogenase reaction?
alcohol aldehyde
NAD
+ NADH + H
+
CH
3
CH ethanol
2
OH alcohol dehydrogenase enzyme
A) Hydrolysis
B) Decarboxylation
C) Oxidation/reduction
D) Acid/base
E) Hydration
O
CH
3
C H ethanal
(acetaldehyde)

64
Reactions of Alcohols and Thiols (Unit 8)

65
Enzymes
The common names for enzymes often describe the substrate (reactant) for the reaction and a description of the reaction that is being carried out on that substrate.
•
The names usually end with -ase .
•
Example: pyruvate decarboxylase

-keto acid
O
CH
3
C
O
C pyruvic acid
OH aldehyde pyruvate decarboxylase
O
CH
3
C H ethanal
(acetaldehyde)
+ CO
2

Question (Clicker)
66
What class of reaction is the pyruvate decarboxylase reaction?

-keto acid aldehyde
O
CH
3
C
O
C pyruvic acid
OH pyruvate decarboxylase
A) Hydrolysis
B) Decarboxylation
C) Oxidation/reduction
D) Acid/base
E) Hydration
O
CH
3
C H ethanal
(acetaldehyde)
+ CO
2

67
Carboxylic Acids & Phenols, Other Reactions
(Unit 7)
The decarboxylation of β-keto acids produces ketones
The decarboxylation of α-keto acids produces aldehydes

68
Enzymes
The common names for enzymes often describe the substrate (reactant) for the reaction and a description of the reaction that is being carried out on that substrate.
•
The names usually end with -ase .
•
Example: succinate dehydrogenase
HO
O O
C CH
2
CH
2
C OH succinic acid
FAD FADH
2 succinate dehydrogenase
HO
O
C
H
C C
H fumaric acid
O
C OH

Question (Clicker)
69
What class of reaction is the alchohol dehydrogenase reaction?
O
O O FAD FADH
2
HO C
H
O
HO C CH
2
CH
2
C OH C C succinate dehydrogenase
H C OH succinic acid fumaric acid
A) Hydrolysis
B) Decarboxylation
C) Oxidation/reduction
D) Acid/base
E) Hydration

70
Oxidation and Reduction (Unit 4)
The reaction equation on the previous slide also illustrates another shorthand method of writing equations, which used
• multiple reaction arrows.
The longhand form of this reaction equation is
O H H O
FAD
O H O
HO C C C C OH HO C C C C OH
H H succinic acid
(saturated)
H fumaric acid
(unsaturated)
O
HO C
H
C
H
C
H H succinic acid
(saturated)
O
C OH + FAD
O
HO C C
H
C
H fumaric acid
(unsaturated)
O
C OH + FADH
2

71
Enzymes
The common names for enzymes often describe the substrate (reactant) for the reaction and a description of the reaction that is being carried out on that substrate.
•
The names usually end with -ase .
•
Example: succinate dehydrogenase
HO
O
C
H
C C
H
O
C OH
+ H
2
O fumaric acid fumarase
HO
O OH O
C CH
2
C
H
L-malic acid
C OH

72
Question (Clicker)
What class of reaction is the fumarase reaction? (Unit 8)
A) Hydrolysis
O
H
B) Decarboxylation
C C
O
+ H
2
O
H C OH
C) Oxidation/reduction fumaric acid
D) Acid/base fumarase
HO
O OH
C CH
2
C
H
L-malic acid
O
C OH
E) Hydration

73
Reactions Involving Water (Unit 4)
Hydration
•
In the hydration reaction water is also split, but instead of being used to split another molecule, it is added to another molecule to produce a single product.
•
•
The water it is added to either an alkene or alkyne:
H OH
The hydration of an alkene produces an alcohol.
H C C H + H OH H C C H acid catalyst
H H H H ethene
(an alkene) ethanol
(an alcohol)

74
Enzymes
Specificity
•
Absolute spectificity - enzyme only accepts one specific substrate.
•
Relative specificity - enzyme accepts a range of related substrates.
alcohol
NAD
+ NADH + H
+
R CH
2 ethanol
OH alcohol dehydrogenase enzyme aldehyde
O
CH
3
C H ethanal
(acetaldehyde)

75
Enzymes
Specificity
•
Stereospecific specificity - enzyme only reacts with or produces one specific stereoisomer
HO
O O
C CH
2
CH
2
C OH succinic acid
FAD FADH
2 succinate dehydrogenase
HO trans
O
C
H
C C
H fumaric acid
O
C OH
+ cis
HO
O
C
H
C C
H
O
C OH maleic acid
HO
O
C
H
C C
H
O
C OH
+ H
2
O fumaric acid fumarase
HO
O OH O
C CH
2
C
H
L-malic acid
C OH + HO
O H O
C CH
2
C
OH
C
D-malic acid
OH

76
Enzymes
Specificity
•
Absolute
•
Relative
•
Stereospecific

77
Enzymes
Catalysis
•
As catalysis, enzyme have no effect on the change in free energy, Δ G, for a reaction
•
Ezymes speed up reactions by decreasing the activation energy, E act
.
•
Enzymes do this by binding the substrates and by directing the reaction

78
Free Energy and Reaction Rates (Unit 4)
There is a third way to speed up the reaction rate and that is to lower the height of the hill.
•
This is done using catalysts , which provide an alternative pathway over the hill for the reactants.
Α → B
Free
Energy
(G)
A
Β
E act
> 0 without catalyst
with catalyst
Δ G < 0 spontaneous
Progress of reaction

79
Enzymes
Catalysis
•
The location on the enzyme where the substrate binds and the reaction occurs is called the active site .
•
Back in Unit 4 we saw a specific example of this with the hexokinase reaction
Explore the enzyme hexokinase

80
Enzymes
Cofactors and Coenzymes
•
Sometimes enzymes need some help with catalzying the reactions.
•
Cofactors are non-protein components of an enzyme
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Metal ions
•
Organic molecules (Coenzymes)
•
Many of the coenzymes are derived from the vitamins that we take in in our diet.

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Enzymes

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Enzymes pH and Temperature
•
Enyzme activity is often critically dependent on the pH and temperature.

83
Control of Enzyme-Catalyzed Reactions
Michaelis-Meten enzymes behave according to a model proposed in the early 1900’s by Michaelis and Menten.
•
E = enyzme
•
S = substrate
•
ES = enzyme-substrate complex
•
P = product

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Control of Enzyme-Catalyzed Reactions
Raymond describes an analogy of reaching into a box for an orgrange, pulling one out, and peeling it.
•
The Michaelis-Menten model is characterized by two parameters.
•
K
M
K
M
V max
(The Michaelis-Menten constant), which is related to the strength of the substrate binding.
•
V max
(The maximum velocity), which corresponds to the maximum rate that the enzyme-substrate complex forms product.

85
Control of Enzyme-Catalyzed Reactions
Enzyme Inhibition
•
Can be a normal event used by the cell to control enzyme activity.
•
Can also be exploited in the design of drugs.
•
Example , the irreversible inhibition of COX enzymes by aspirin

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Control of Enzyme-Catalyzed Reactions
Enzyme Inhibition can also be Reversible
•
Competitive inhibition
•
The inhibitor competes with the substrate for the active site
K
M
V max
Competitive inhibition affect
K
M but not V max

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Control of Enzyme-Catalyzed Reactions
Some drugs are competitive inhibitors of enzymes
•
Example: the anti-HIV drug AZT
•
The AZT inhibits the enzyme reverse trascriptase enzyme , which the HIV virus uses to converts it RNA to DNA. The drug mimics the normal substrate for this enzyme, dTTP.
•
This drug targets the activity of the HIV virus because humans do not use a reverse transcriptase enzyme.

88
Control of Enzyme-Catalyzed Reactions
Some drugs are competitive inhibitors of enzymes
•
Example: the bacterial drug sufanilamide (a sulfa drug).
•
The sufanilamide inhibits the an enzyme that bacteria use to synthesize the coenzyme folate. The drug mimics the normal substrate for this enzyme, p -aminobenoate.

Control of Enzyme-Catalyzed Reactions
•
This drug targets the activity of bacteria because humans do not synthesize their own folate, getting it instead from their diet.
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Folate

90
Control of Enzyme-Catalyzed Reactions
Enzyme Inhibition can also be Reversible
•
Noncompetitive inhibition
•
The inhibitor binds at a different site thatn the substrate.
K
M
V max
Noncompetitive inhibition affects
V max but not K
M

91
Control of Enzyme-Catalyzed Reactions
Noncompetitive inhibition is often used to regulate biosynthetic pathways by a mechanism called feedback inhibition .
•
The end product of the pathway binds to a site on an enzyme used earlier in the pathway, and turns it off.

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Control of Enzyme-Catalyzed Reactions
Enzymes that are inhibited by a substance binding to a site other than the active site are called allosteric enzymes .
•
The enzymes that are regulated by noncompetive inhibition in feedback inhibition are examples of allosteric enzyme.
•
The substance that inhibits the enzyme in this way is called a negative effector .
Some allosteric enzymes are activated instead of inhibited by as substance binding at their allosteric site.
•
These substances are called positive effectors .

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Control of Enzyme-Catalyzed Reactions
Some enzymes are controlled by covalent modifications to their structure.
•
In some cases the modifications are reversible, such as placing a phosphate on an enzyme to turn it on, and then taking the phosphate off to turn it off again.

94
Control of Enzyme-Catalyzed Reactions
Some enzymes are controlled by covalent modifications to their structure.
•
Example: Glycogen phosphorylase, which is the enzyme that breaks down the polysaccharide glycogen.
•
The phosphorylation/dephosphorylation of this enzyme is under hormonal control.

95
Control of Enzyme-Catalyzed Reactions
Some enzymes are controlled by covalent modifications to their structure
•
In other cases the covalent modification is irreversible.

96
Control of Enzyme-Catalyzed Reactions
Some enzymes are controlled by covalent modifications to their structure
•
Example: the digestive enzymes trypsin and chymotrypsin, which are used to break down proteins in the small intestine are synthesized in the pancreas in an inactive form called trypsinogen and chymotrypsinogen, respectively.
•
They are transported in this inactive form to the small intestine, there are activated by removing parts of their amino acids sequence.

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Control of Enzyme-Catalyzed Reactions
In a clinical setting, the presence of enzymes in blood is often used to diagnose tissue damage that is related to various diseases.