Chem 150Chem 150Unit 10 - Unit 10 - BiologicalBiological Molecules III Molecules IIIPeptides, Proteins and EnzymesPeptides, Proteins and Enzymes
Proteins are the workhorses in living systems. Proteins are the workhorses in living systems. Their many roles include providing structure, Their many roles include providing structure, catalyzing nearly all the reactions that take catalyzing nearly all the reactions that take
place in a living cell, transporting and storing place in a living cell, transporting and storing materials, and controlling and defending living materials, and controlling and defending living
systems. Like carbohydrates, proteins are systems. Like carbohydrates, proteins are polymers, but unlike the polysaccharides, proteins polymers, but unlike the polysaccharides, proteins
are able to assume a much wider range of 3-are able to assume a much wider range of 3-dimensional structures and a functions. In this dimensional structures and a functions. In this
unit we will focus on one the of the most unit we will focus on one the of the most important functions of proteins; that of important functions of proteins; that of
biological catalysts (enzymes).biological catalysts (enzymes).
22
Amino AcidsAmino Acids
αα-Amino acids are the building blocks (monomers) for -Amino acids are the building blocks (monomers) for polypeptides and proteins.polypeptides and proteins.
• Every amino acid contains,Every amino acid contains,• A carboxylic acid groupA carboxylic acid group• An amino groupAn amino group• A side chain (R)A side chain (R)
33
Amino AcidsAmino Acids
Back in Unit 7 we saw that carboxylic acids behave as acids Back in Unit 7 we saw that carboxylic acids behave as acids when dissolved in water. when dissolved in water.
44
Question (Clickers) (Unit 7)Question (Clickers) (Unit 7)
At At pHpH 7, which will be the predominant species? 7, which will be the predominant species?
A)A) Carboxylic acidCarboxylic acid
B)B) Carboxylate ionCarboxylate ion
CH3 C
O
OH + H2O CH3 C
O
O + H3O+
acid acidbasebase
CH3 C
O
OH + H2O CH3 C
O
O + H3O+
acid acidbasebase
pKpKaa ≈ 5 ≈ 5pKpKaa ≈ 5 ≈ 5
carboxylic acidcarboxylic acidcarboxylic acidcarboxylic acid carboxylate ioncarboxylate ioncarboxylate ioncarboxylate ion
55
Carboxylic Acids & Phenols as Weak Acids Carboxylic Acids & Phenols as Weak Acids (Unit 7)(Unit 7)
• At At pHpH 7, the carboxylate ion of carboxylic acids predominate 7, the carboxylate ion of carboxylic acids predominate
• At At pH = pKpH = pKa a
• At At pH < pKpH < pKaa
• At At pH > pKpH > pKaa
CH3 C
O
OH + H2O CH3 C
O
O + H3O+
acid acidbasebase
CH3 C
O
OH + H2O CH3 C
O
O + H3O+
acid acidbasebase
pKpKaa ≈ 5 ≈ 5pKpKaa ≈ 5 ≈ 5pHpH = 7 = 7pHpH = 7 = 7
CH3 C
O
OH
acid
CH3 C
O
O
base
=CH3 C
O
OH
acid
CH3 C
O
O
base
=
CH3 C
O
OH
acid
CH3 C
O
O
base
>CH3 C
O
OH
acid
CH3 C
O
O
base
>
CH3 C
O
OH
acid
CH3 C
O
O
base
<CH3 C
O
OH
acid
CH3 C
O
O
base
<
66
Amino AcidsAmino Acids
Back in Unit 7 we also saw that amines behave as bases Back in Unit 7 we also saw that amines behave as bases when dissolved in water.when dissolved in water.
77
Amines as Weak Bases (Unit 7)Amines as Weak Bases (Unit 7)
Like ammonia, 1°, 2° and 3°, act as Brønsted-Lowry bases.Like ammonia, 1°, 2° and 3°, act as Brønsted-Lowry bases.
+ H2O (l) + OH- (aq)N H (aq)
H
CH3 N H (aq)
H
CH3
H
methanamine(base)
methylammonium ion(acid)
+ H2O (l) + OH- (aq)N H (aq)
H
CH3 N H (aq)
H
CH3
H
methanamine(base)
methylammonium ion(acid)
88
Amines as Weak Bases (Unit 7)Amines as Weak Bases (Unit 7)
The conjugate acids are called ammonium ionsThe conjugate acids are called ammonium ions• When placed in water, these ammonium ions will behave When placed in water, these ammonium ions will behave
like acids.like acids.
+ H3O+ (aq)+ H2O (l) N H (aq)
H
CH3N H (aq)
H
CH3
H
methanamine(base)
methylammonium ion(acid)
pKa ≈ 10+ H3O+ (aq)+ H2O (l) N H (aq)
H
CH3N H (aq)
H
CH3
H
methanamine(base)
methylammonium ion(acid)
pKa ≈ 10
99
Amino AcidsAmino Acids
At At pHpH 7, amino acids are in their 7, amino acids are in their zwitterionic zwitterionic form.form.• There is no There is no pHpH value at which value at which
there are no charges on an there are no charges on an amino acids.amino acids.
• However, there is a However, there is a pHpH value at value at which the which the net chargenet charge is zero. is zero.• This This pHpH value is called the value is called the
isoelectric pointisoelectric point..
Net chargeNet chargeNet chargeNet charge
+1+1+1+1
0000
-1-1-1-1
1010
Amino AcidsAmino Acids
There are 20 different sidechains for the amino acids that are There are 20 different sidechains for the amino acids that are used to build proteins.used to build proteins.
• These are classified according to their physical properties These are classified according to their physical properties asas
• Non-polarNon-polar
• Polar acidic (negatively charged at Polar acidic (negatively charged at pHpH 7) 7)
• Polar basic (positively charged at Polar basic (positively charged at pHpH 7) 7)
• Polar neutral (polar, but not charged at Polar neutral (polar, but not charged at pHpH 7) 7)
1111
Non polar Non polar sidechainssidechains• Most of these Most of these
sidechains sidechains are are hydrocarbonshydrocarbons
Amino AcidsAmino Acids
1212
Polar acidic sidechainsPolar acidic sidechains• Sidechains contain Sidechains contain
carboxylic acidscarboxylic acids• Negatively charged Negatively charged
at at pH 7pH 7
Amino AcidsAmino Acids
1313
Polar basic sidechainsPolar basic sidechains• Sidechains contain Sidechains contain
aminesamines• Positively charged at Positively charged at pHpH 7 7
Amino AcidsAmino Acids
1414
Polar neutral sidechainsPolar neutral sidechains• Sidechains contain polar Sidechains contain polar
groups that are capable of groups that are capable of hydrogen bondinghydrogen bonding• alcoholsalcohols• phenolsphenols• amidesamides
• Uncharged at Uncharged at pHpH 7 7
Amino AcidsAmino Acids
1515
For all of the amino acids, except one (glycine), the For all of the amino acids, except one (glycine), the αα-carbon -carbon is chiral.is chiral.• Fisher projection of the amino acids alanine:Fisher projection of the amino acids alanine:
• With few exceptions, only the With few exceptions, only the LL-amino acids are used to -amino acids are used to make proteins.make proteins.
Amino AcidsAmino Acids
1616
Peptides, Proteins, and Peptides, Proteins, and pHpH
Amino acids are joined together to form polymers of amino Amino acids are joined together to form polymers of amino acids called acids called oligopeptidesoligopeptides (2-10 amino acids) and (2-10 amino acids) and polypeptides polypeptides (more than 10 amino acids).(more than 10 amino acids).
• Collectively, oligopeptides and polypeptides are called Collectively, oligopeptides and polypeptides are called peptidespeptides..
• The amino acids are joind together by an amide bond The amino acids are joind together by an amide bond called a called a peptide bondpeptide bond, which is analogous to the , which is analogous to the glycosidic bond found in oligosaccharides and glycosidic bond found in oligosaccharides and polysaccharides.polysaccharides.
• Back in Unit 7 we saw how carboxylic acids can react with Back in Unit 7 we saw how carboxylic acids can react with ammonia and amines to form amides.ammonia and amines to form amides.
1717
Amides (Unit 7)Amides (Unit 7)
• When a carboxylic acid reacts with an amine it also When a carboxylic acid reacts with an amine it also produces and ammonium saltproduces and ammonium salt
• If the ammonium salt is then heated, an If the ammonium salt is then heated, an amideamide is is produced.produced.
1818
Amides (Unit 7)Amides (Unit 7)
Amides are important in Amides are important in biochemistry.biochemistry.• For example, amino For example, amino
acids are connected acids are connected together to form together to form proteins using amide proteins using amide groups.groups.
amino acidamino acidamino acidamino acid
1919
Peptide bond formationPeptide bond formation
Peptides, Proteins, and Peptides, Proteins, and pHpH
H3NC
C
OH
H
O NC
C
H OH
CH2
OH H+ H3NC
CN
CC
O
H
O
O
H
HH
CH2
+ H O HH3NC
C
OH
H
O NC
C
H OH
CH2
OH H+ H3NC
CN
CC
O
H
O
O
H
HH
CH2
+ H O H
Peptide BondPeptide BondPeptide BondPeptide Bond
DipeptideDipeptideDipeptideDipeptide
2020
Peptides, Proteins, and pHPeptides, Proteins, and pH
• The amide bond that The amide bond that connects the amino connects the amino acids together in a acids together in a peptide is called a peptide is called a peptide bondpeptide bond..
• ProteinsProteins are long are long polypeptide chains, polypeptide chains, usually with 50 or usually with 50 or more amino acids, more amino acids, which fold into a well which fold into a well defined structure.defined structure. The proteinThe protein
ubiquitinubiquitinThe proteinThe protein
ubiquitinubiquitin
2121
Peptides, Proteins, and pHPeptides, Proteins, and pH
Proteins are sensitive to the Proteins are sensitive to the pHpH because they contain because they contain numberous acid and base groupsnumberous acid and base groups• The The pHpH affects the charge on a proteins, which in turn, can affects the charge on a proteins, which in turn, can
have a marked effect on a protein’s structure and function.have a marked effect on a protein’s structure and function.
2222
Peptides, Proteins, and pH
Peptides, Proteins, and pH
ExampleExample• The charges on The charges on
the tripeptidethe tripeptideLys-Ser-AsnLys-Ser-Asnas a function of as a function of pHpH..
Net ChargeNet ChargeNet ChargeNet Charge
+2+2+2+2
0000
-2-2-2-2
2323
Peptides, Proteins, and pH
Peptides, Proteins, and pH
ExampleExample• The charges on The charges on
the tripeptidethe tripeptideLys-Lys-AlaLys-Lys-Alaas a function of as a function of pHpH..
Net ChargeNet ChargeNet ChargeNet Charge
+3+3+3+3
+2+2+2+2
-1-1-1-1
2424
Amino acids with acid or base side chains have additional Amino acids with acid or base side chains have additional charge groups:charge groups:
• e.g. e.g. Glutamic acid Glutamic acid is an acid amino acidis an acid amino acid
• At At pHpH’s below the isoionic point (’s below the isoionic point (pIpI) the charge is positive) the charge is positive
• At At pHpH’s above the isoionic point (’s above the isoionic point (pIpI), the charge is negative), the charge is negative
Peptides, Proteins, and pH
pIpI = 3.2 = 3.2pIpI = 3.2 = 3.2
H3N C
H
C
O
OH
CH2
CH2
C
OH–
H+
pH < 2
+1
O
OH
H3N C
H
C
O
O
CH2
CH2
C
OH–
H+
2 < pH < 4.4
0
O
OH
H3N C
H
C
O
O
CH2
CH2
C
OH–
H+
4.4 < pH < 9
-1
O
O
H2N C
H
C
O
O
CH2
CH2
C
9 < pH
-2
O
O
2525
Peptides, Proteins, and pH
Amino acids with acid or base side chains have additional Amino acids with acid or base side chains have additional charge groups:charge groups:
• e.g. e.g. Lysine Lysine is a basic amino acidis a basic amino acid
• At At pHpH’s below the isoionic point (’s below the isoionic point (pIpI) the charge is positive) the charge is positive
• At At pHpH’s above the isoionic point (’s above the isoionic point (pIpI), the charge is negative), the charge is negative
H3N C
H
C
O
OH
CH2
CH2
CH2
CH2
NH3
OH–
H+H3N C
H
C
O
O
CH2
CH2
CH2
CH2
NH3
OH–
H+H2N C
H
C
O
O
CH2
CH2
CH2
CH2
NH3
OH–
H+H2N C
H
C
O
O
CH2
CH2
CH2
CH2
NH2
pH < 2 2 < pH < 9 9 < pH < 10.3 10.3 < pH
+2 +1 0 -1
pI = 9.7pI = 9.7pI = 9.7pI = 9.7
2626
Peptides, Proteins, and pH
We are going to simplify the determination of charge as a We are going to simplify the determination of charge as a function of function of pHpH by looking only at by looking only at pHpH 1, 1, pH pH 7, and 7, and pHpH 14: 14:
Charges at different pH Charges at different pH valuesvalues pHpH 1 1 pH pH 77 pH pH 1414
AcidsAcidsAA
Include:Include:αα-COOH-COOH
Asp sidechainAsp sidechainGlu sidechainGlu sidechain
00 -1-1 -1-1
BasesBasesBB
Includes:Includes:αα-NH-NH
22
His sidechainHis sidechainLys sidechainLys sidechainArg sidechainArg sidechain
+1+1 +1+1 00
2727
QuestionQuestion
At At pH 7pH 7, which of the following amino acids have a net , which of the following amino acids have a net positive charge, which have a net negative charge, and which positive charge, which have a net negative charge, and which are neutral?are neutral?
LysineLysine
PhenylalaninePhenylalanine
LeucineLeucine
2828
QuestionQuestion
LysineLysine
C C
H
H2N
O
OH
CH2
CH2
CH2
CH2
NH2
BBBB
BBBB
AAAA Charges at Charges at different pH valuesdifferent pH values pHpH 1 1 pH pH 77 pH pH 1414
AA αα-COOH-COOH 00 -1-1 -1-1
BB αα-NH-NH22 +1+1 +1+1 00
BB Lys sidechainLys sidechain +1+1 +1+1 00
NetNet +2+2 +1+1 -1-1
2929
QuestionQuestion
Draw the structure of the following tripeptide Draw the structure of the following tripeptide Glu-Asp-PheGlu-Asp-Phe at at pHpH 1 and high 1 and high pH pH 1414. .
3030
QuestionQuestion
Draw the structure of the following tripeptide Draw the structure of the following tripeptide Glu-Asp-PheGlu-Asp-Phe at at pHpH 1 and high 1 and high pH pH 1414. .
H2N C C N C C N C C
H H HO O O
OH
R R RH H
H2N C C N C C N C C
H H HO O O
OH
R R RH H
Draw the backboneDraw the backboneDraw the backboneDraw the backbone
3131
QuestionQuestion
Draw the structure of the following tripeptide Draw the structure of the following tripeptide Glu-Asp-PheGlu-Asp-Phe at at pHpH 1 and high 1 and high pH pH 1414..
H2N C C N C C N C C
H H HO O O
OH
CH2 CH2 CH2H H
CH2
C
O OH
C
O OH
Glutamic Acid(Glu)
Aspartic acid(Asp)
Phenylalanine(Phe)
BBBB AAAA
AAAAAAAA
Add the sidechains and identify the acids (Add the sidechains and identify the acids (AA) and bases () and bases (BB))Add the sidechains and identify the acids (Add the sidechains and identify the acids (AA) and bases () and bases (BB))
3232
Draw the structure of the following tripeptide Draw the structure of the following tripeptide Glu-Asp-PheGlu-Asp-Phe at at pHpH 1 and high 1 and high pH pH 1414..
QuestionQuestion
H3N C C N C C N C C
H H HO O O
OH
CH2 CH2 CH2H H
CH2
C
O OH
C
O OH
Glutamic Acid(Glu)
Aspartic acid(Asp)
Phenylalanine(Phe)
BBBB AAAA
AAAAAAAA
At At pH pH 11, Acids (, Acids (AA) are 0 and Bases () are 0 and Bases (BB) are +1) are +1At At pH pH 11, Acids (, Acids (AA) are 0 and Bases () are 0 and Bases (BB) are +1) are +1
Net Charge = +1Net Charge = +1at at pHpH 1 1
Net Charge = +1Net Charge = +1at at pHpH 1 1
3333
Draw the structure of the following tripeptide Draw the structure of the following tripeptide Glu-Asp-PheGlu-Asp-Phe at at pHpH 1 and high 1 and high pH pH 1414..
QuestionQuestion
BBBB AAAA
AAAAAAAA
H2N C C N C C N C C
H H HO O O
O
CH2 CH2 CH2H H
CH2
C
O O
C
O O
Glutamic Acid(Glu)
Aspartic acid(Asp)
Phenylalanine(Phe)
At At pH pH 1414, Acids (, Acids (AA) are -1 and Bases () are -1 and Bases (BB) are 0) are 0At At pH pH 1414, Acids (, Acids (AA) are -1 and Bases () are -1 and Bases (BB) are 0) are 0
Net Charge = -3Net Charge = -3at at pHpH 14 14
Net Charge = -3Net Charge = -3at at pHpH 14 14
3434
Protein StructureProtein Structure
Proteins are polypeptides that fold to adopt a well-defined, Proteins are polypeptides that fold to adopt a well-defined, three-dimensional structure.three-dimensional structure.
There two general classifications of proteinsThere two general classifications of proteins
• Fibrous proteinsFibrous proteins exist as long fibers that are usually exist as long fibers that are usually tough and insoluble in water; examples includetough and insoluble in water; examples include• collagen (skin and bones)collagen (skin and bones)• Keratin (hair)Keratin (hair)
• Globular proteinsGlobular proteins are spherical, highly folded, and usually are spherical, highly folded, and usually soluble in water; examples includesoluble in water; examples include• enzymesenzymes• antibodiesantibodies• transport proteins like hemoglobin and myoglobintransport proteins like hemoglobin and myoglobin
3535
Fibrous versus globularFibrous versus globular
Protein StructureProtein Structure
3636
Protein StructureProtein Structure
Proteins display up to four levels of structureProteins display up to four levels of structure
• Primary structurePrimary structure• This is the amino acid sequence, which is unique for each proteinThis is the amino acid sequence, which is unique for each protein• This defines the covalent structure of a proteinThis defines the covalent structure of a protein
• Secondary structureSecondary structure• Regular, periodic structures, that involve hydrogen bonding between Regular, periodic structures, that involve hydrogen bonding between
the backbone amidesthe backbone amides
N C
H
C
O
H R RH
N
O
C
H
CN
H
O
N C
H
C
O
H RRH
C
O
C
H
CN
hydrogen bondsbetween amides
3737
Protein StructureProtein Structure
Proteins display up to four Proteins display up to four levels of structurelevels of structure
• Tertiary structureTertiary structure
• The 3-dimensional fold of the The 3-dimensional fold of the the polypeptide in which the the polypeptide in which the backbone twists and turns its backbone twists and turns its way through the folded structure way through the folded structure of the protein.of the protein.
• It involves interactions between It involves interactions between the sidechains of the the amino the sidechains of the the amino acids and is highly influenced by acids and is highly influenced by the amino acid sequence.the amino acid sequence. The proteinThe protein
ubiquitinubiquitinThe proteinThe protein
ubiquitinubiquitin
3838
Primary StructurePrimary Structure
• A protein’s amino acid sequence is referred to as its A protein’s amino acid sequence is referred to as its primary structureprimary structure..
• Every protein has a unique primary structure that is Every protein has a unique primary structure that is determined by the gene for that protein.determined by the gene for that protein.
• The primary structure defines the covalent structure The primary structure defines the covalent structure of a protein.of a protein.
Protein StructureProtein Structure
3939
Primary StructurePrimary Structure
Protein StructureProtein Structure
N-TerminusN-TerminusN-TerminusN-Terminus
C-TerminusC-TerminusC-TerminusC-Terminus
H3NC
CN
CC
NC
CN
CC
NC
CN
CC
NC
CN
CC
O
H
H
H
H
H
H
H
O
O
O
O
O
O
O
O
H
H
H
H
H
H
H
HH
CH2
CH3
CH2
HC CH3
CH3
CH2
OH
CH2
CH2
CH2
CH2
NH3
CH2
CO O
CH2
CH2
CO NH2
H3NC
CN
CC
NC
CN
CC
NC
CN
CC
NC
CN
CC
O
H
H
H
H
H
H
H
O
O
O
O
O
O
O
O
H
H
H
H
H
H
H
HH
CH2
CH3
CH2
HC CH3
CH3
CH2
OH
CH2
CH2
CH2
CH2
NH3
CH2
CO O
CH2
CH2
CO NH2
GlycineGlycineGlyGly
GlycineGlycineGlyGly
PhenylalaninePhenylalaninePhePhe
PhenylalaninePhenylalaninePhePhe
AlanineAlanineAlaAla
AlanineAlanineAlaAla
LeucineLeucineLeuLeu
LeucineLeucineLeuLeu
SerineSerineSerSer
SerineSerineSerSer
LysineLysineLysLys
LysineLysineLysLys
Aspartic AcidAspartic AcidAspAsp
Aspartic AcidAspartic AcidAspAsp
GluctamineGluctamineGlnGln
GluctamineGluctamineGlnGln
4040
Primary StructurePrimary Structure
Protein StructureProtein Structure
N-TerminusN-TerminusN-TerminusN-Terminus
C-TerminusC-TerminusC-TerminusC-Terminus
H3NC
CN
CC
NC
CN
CC
NC
CN
CC
NC
CN
CC
O
H
H
H
H
H
H
H
O
O
O
O
O
O
O
O
H
H
H
H
H
H
H
HH
CH2
CH3
CH2
HC CH3
CH3
CH2
OH
CH2
CH2
CH2
CH2
NH3
CH2
CO O
CH2
CH2
CO NH2
H3NC
CN
CC
NC
CN
CC
NC
CN
CC
NC
CN
CC
O
H
H
H
H
H
H
H
O
O
O
O
O
O
O
O
H
H
H
H
H
H
H
HH
CH2
CH3
CH2
HC CH3
CH3
CH2
OH
CH2
CH2
CH2
CH2
NH3
CH2
CO O
CH2
CH2
CO NH2
HH22H-Gly-Phe-Ala-Leu-Ser-Lys-Asp-Gln-COOHH-Gly-Phe-Ala-Leu-Ser-Lys-Asp-Gln-COOHHH
22H-Gly-Phe-Ala-Leu-Ser-Lys-Asp-Gln-COOHH-Gly-Phe-Ala-Leu-Ser-Lys-Asp-Gln-COOH
Gly-Phe-Ala-Leu-Ser-Lys-Asp-GlnGly-Phe-Ala-Leu-Ser-Lys-Asp-GlnGly-Phe-Ala-Leu-Ser-Lys-Asp-GlnGly-Phe-Ala-Leu-Ser-Lys-Asp-GlnGFALSKDQGFALSKDQGFALSKDQGFALSKDQ
GlycylphenylalanylalanylleucylseryllysylaspartylglutamGlycylphenylalanylalanylleucylseryllysylaspartylglutamineine
GlycylphenylalanylalanylleucylseryllysylaspartylglutamGlycylphenylalanylalanylleucylseryllysylaspartylglutamineine
4141
Primary structurePrimary structure• The Central DogmaThe Central Dogma• DNA → mRNA → PolypeptideDNA → mRNA → Polypeptide
Protein StructureProtein Structure
•The genetic code is The genetic code is used to match up the used to match up the DNA/mRNA sequence DNA/mRNA sequence to the sequence of to the sequence of amino acids in a proteinamino acids in a protein
•All living organisms use All living organisms use the same codethe same code
•The genetic code is The genetic code is used to match up the used to match up the DNA/mRNA sequence DNA/mRNA sequence to the sequence of to the sequence of amino acids in a proteinamino acids in a protein
•All living organisms use All living organisms use the same codethe same code
4242
• The functional diversity of proteins results from the large The functional diversity of proteins results from the large number of possible proteins that can be built using the 20 number of possible proteins that can be built using the 20 different amino acidsdifferent amino acids
• QuestionQuestion: How much mass would it take to construct one : How much mass would it take to construct one molecule each of all of the possible polypeptides molecule each of all of the possible polypeptides containing 100 amino acids residues?containing 100 amino acids residues?
• View the polypeptides as beads on a string, with one of 20 possible View the polypeptides as beads on a string, with one of 20 possible types of beads at each position.types of beads at each position.
Protein StructureProtein Structure
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-oo-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-oo-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-oo-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
4343
The Earth weighs 6.0 x 10The Earth weighs 6.0 x 102727
g, how many Earths would it g, how many Earths would it take?take?
Protein StructureProtein Structure
4444
The Sun weighs 2.0 x The Sun weighs 2.0 x 10103333
g g, how many Suns would it take?, how many Suns would it take?
Protein StructureProtein Structure
4545
The Milky Way galaxy weighs 1.2 x 10The Milky Way galaxy weighs 1.2 x 104545
times the mass of times the mass of the sunthe sun
• (1.2 x 10(1.2 x 104545 sunssuns)(2.0 x 10)(2.0 x 103333 g/sun) = 2.4 x 10 g/sun) = 2.4 x 107878 g g
•HowHow may galaxies would it take? may galaxies would it take?
Protein StructureProtein Structure
4646
The Coma galaxy cluster contains several thousand galaxies, The Coma galaxy cluster contains several thousand galaxies, how many ...?how many ...?
Protein StructureProtein Structure
4747
Protein StructureProtein Structure
Number of polypeptides Number of polypeptides (20(20100100)) 1.26 x 101.26 x 10130130
Avg. Mass of each Avg. Mass of each polypeptidepolypeptide 1.83 x 101.83 x 10-22-22
gg
Total mass neededTotal mass needed 2.322.32 x 10 x 10108108 gg
Number of EarthsNumber of Earths 3.9 x 103.9 x 108080
Number of SunsNumber of Suns 1.2 x 101.2 x 107575
Number of GalaxiesNumber of Galaxies 9.7 x 109.7 x 102929
4848
Protein StructureProtein Structure
Secondary structureSecondary structure• The polypeptide backbone can take on regular shapes that The polypeptide backbone can take on regular shapes that
allow the backbone amides to hydrogen bond to one allow the backbone amides to hydrogen bond to one another.another.
• The primary forms of secondary structure includeThe primary forms of secondary structure include• αα-helix-helix• ββ-sheet-sheet
4949
Secondary structure Secondary structure
Protein StructureProtein Structure
α-Helixα-Helixα-Helixα-Helix
5050
Secondary Structure Secondary Structure
Protein StructureProtein Structure
β-Sheetβ-Sheetβ-Sheetβ-Sheet
5151
Secondary StructureSecondary Structure
Protein Secondary StructureProtein Secondary Structure
Antiparallel β-SheetAntiparallel β-SheetAntiparallel β-SheetAntiparallel β-Sheet
5252
Secondary Structure Secondary Structure
Protein StructureProtein Structure
Parallel β-SheetParallel β-SheetParallel β-SheetParallel β-Sheet
5353
Protein StructureProtein Structure
Tertiary StructureTertiary Structure
• The different elements of The different elements of secondary structure come secondary structure come together to create the together to create the overall 3-dimensional overall 3-dimensional structure of the the proteinstructure of the the protein
• The structure is stabilized The structure is stabilized primarily by sidechain primarily by sidechain interactions and is highly interactions and is highly influenced by the amino influenced by the amino acid sequence (primary acid sequence (primary structure).structure).
The proteinThe proteinubiquitinubiquitin
The proteinThe proteinubiquitinubiquitin
5454
Protein StructureProtein Structure
Tertiary StructureTertiary Structure
• This is usually the This is usually the nativenative, , or biologically active, form or biologically active, form of the protein.of the protein.
• When placed in water, the When placed in water, the polypeptide folds to polypeptide folds to maximize the number of maximize the number of nonpolar (hydrophobic) nonpolar (hydrophobic) residues that are buried residues that are buried on the inside away from on the inside away from exposure to water.exposure to water. The proteinThe protein
ubiquitinubiquitinThe proteinThe protein
ubiquitinubiquitin
5555
Protein StructureProtein Structure
Tertiary StructureTertiary Structure
The proteinThe proteinubiquitinubiquitin
The proteinThe proteinubiquitinubiquitin
Explore thetertiary structureand thesecondary structure of the protein ubiqu
itin
Explore thetertiary structureand thesecondary structure of the protein ubiqu
itin
5656
Protein StructureProtein Structure
Tertiary StructureTertiary Structure• The tertiary structure is stabilized by the same non-The tertiary structure is stabilized by the same non-
covalent interactions that we looked at in determining covalent interactions that we looked at in determining boiling points and solubilitesboiling points and solubilites• Charge/Charge interactions (Salt bridges)Charge/Charge interactions (Salt bridges)• Ion/Dipole interactionsIon/Dipole interactions• Dipole/Dipole interactionsDipole/Dipole interactions• Hydrogen bondingHydrogen bonding• Hydrophobic interactions (nonpolor/water)Hydrophobic interactions (nonpolor/water)
• There is one covalent interactions that stabilizes the There is one covalent interactions that stabilizes the tertiary structure of some proteins.tertiary structure of some proteins.• Disufide bondDisufide bond
5757
Protein StructureProtein Structure
Tertiary StructureTertiary Structure• The interactions that The interactions that
stabilize the tertiary stabilize the tertiary structure.structure.
5858
Protein StructureProtein Structure
Quaternary StructureQuaternary Structure• Some proteins contain multiple Some proteins contain multiple
polypeptidespolypeptides• Each peptide is called a subunitEach peptide is called a subunit
• The polypeptides are held The polypeptides are held together by the same types of together by the same types of interactions that stabilize the interactions that stabilize the tertiary structure.tertiary structure.Explore thequaternary structur
e of the protein ubiquitin
Explore thequaternary structure of the protein ubiquit
in
5959
Protein DenaturationProtein Denaturation
Because the secondary, tertiary and quaternary structures of Because the secondary, tertiary and quaternary structures of proteins are stabilized by weak, non-covalent interactions, proteins are stabilized by weak, non-covalent interactions, these structures are easily disrupted by agents that disrupt these structures are easily disrupted by agents that disrupt theses interactions, including:theses interactions, including:• Changes in temperatureChanges in temperature• Changes in Changes in pHpH• Mechanical stress (agitation)Mechanical stress (agitation)• Soaps and detergentsSoaps and detergentsThese agents typically cause the protein to unfoldThese agents typically cause the protein to unfold• Only the primary structure remainsOnly the primary structure remains• The protein loses it functionThe protein loses it functionThe process is called The process is called protein denaturationprotein denaturation..
6060
Protein DenaturationProtein Denaturation
Christain Anfinsen won a Nobel Prize for showing that protein Christain Anfinsen won a Nobel Prize for showing that protein denaturation can be reversed.denaturation can be reversed.• The experiment demonstrated that the information necessary The experiment demonstrated that the information necessary
to obtain the correctly folded protein structure is contained to obtain the correctly folded protein structure is contained within the protein’s amino acid sequence (primary structure).within the protein’s amino acid sequence (primary structure).
ActiveActiveProteinProteinActiveActiveProteinProtein
InactiveInactiveProteinProteinInactiveInactiveProteinProtein
6161
EnzymesEnzymes
Nearly every reaction that takes place in a living cell has an Nearly every reaction that takes place in a living cell has an enzyme associated with it.enzyme associated with it.
• Enzymes are biological catalystsEnzymes are biological catalysts
• Most enzymes are proteinsMost enzymes are proteins
Many human diseases involve enzymes misbehavingMany human diseases involve enzymes misbehaving
• Many treatments for diseases involve drugs that target Many treatments for diseases involve drugs that target enzymes.enzymes.
6262
EnzymesEnzymes
The common names for enzymes often describe the The common names for enzymes often describe the substratesubstrate (reactant) for the reaction and a description of the (reactant) for the reaction and a description of the reaction that is being carried out on that substrate.reaction that is being carried out on that substrate.
• The names usually end with The names usually end with -ase-ase..
• Example: Example: alcohol dehydrogenasealcohol dehydrogenase
CH3 CH2 OH
NAD+ NADH + H+
CH3 C H
O
ethanol ethanal(acetaldehyde)
alcohol aldehyde
alcohol dehydrogenaseenzyme
CH3 CH2 OH
NAD+ NADH + H+
CH3 C H
O
ethanol ethanal(acetaldehyde)
alcohol aldehyde
alcohol dehydrogenaseenzyme
6363
Question (Clicker)Question (Clicker)
What class of reaction is the alcohol dehydrogenase What class of reaction is the alcohol dehydrogenase reaction?reaction?
A)A) HydrolysisHydrolysis
B)B) DecarboxylationDecarboxylation
C)C) Oxidation/reductionOxidation/reduction
D)D) Acid/baseAcid/base
E)E) HydrationHydration
CH3 CH2 OH
NAD+ NADH + H+
CH3 C H
O
ethanol ethanal(acetaldehyde)
alcohol aldehyde
alcohol dehydrogenaseenzyme
CH3 CH2 OH
NAD+ NADH + H+
CH3 C H
O
ethanol ethanal(acetaldehyde)
alcohol aldehyde
alcohol dehydrogenaseenzyme
6464
Reactions of Alcohols and Thiols (Unit 8)Reactions of Alcohols and Thiols (Unit 8)
6565
EnzymesEnzymes
The common names for enzymes often describe the The common names for enzymes often describe the substratesubstrate (reactant) for the reaction and a description of the (reactant) for the reaction and a description of the reaction that is being carried out on that substrate.reaction that is being carried out on that substrate.
• The names usually end with The names usually end with -ase-ase..
• Example: Example: pyruvate decarboxylasepyruvate decarboxylase
CH3 C
O
C
O
OH
α-keto acid
CH3 C H
O
ethanal(acetaldehyde)
aldehyde
+ CO2
pyruvic acidpyruvate
decarboxylase
CH3 C
O
C
O
OH
α-keto acid
CH3 C H
O
ethanal(acetaldehyde)
aldehyde
+ CO2
pyruvic acidpyruvate
decarboxylase
6666
Question (Clicker)Question (Clicker)
What class of reaction is the pyruvate decarboxylase What class of reaction is the pyruvate decarboxylase reaction?reaction?
A)A) HydrolysisHydrolysis
B)B) DecarboxylationDecarboxylation
C)C) Oxidation/reductionOxidation/reduction
D)D) Acid/baseAcid/base
E)E) HydrationHydration
CH3 C
O
C
O
OH
α-keto acid
CH3 C H
O
ethanal(acetaldehyde)
aldehyde
+ CO2
pyruvic acidpyruvate
decarboxylase
CH3 C
O
C
O
OH
α-keto acid
CH3 C H
O
ethanal(acetaldehyde)
aldehyde
+ CO2
pyruvic acidpyruvate
decarboxylase
6767
Carboxylic Acids & Phenols, Other Reactions Carboxylic Acids & Phenols, Other Reactions (Unit 7)(Unit 7)
The decarboxylation of The decarboxylation of ββ-keto acids produces -keto acids produces ketonesketones
The decarboxylation of The decarboxylation of αα-keto acids produces -keto acids produces aldehydesaldehydes
6868
EnzymesEnzymes
The common names for enzymes often describe the The common names for enzymes often describe the substratesubstrate (reactant) for the reaction and a description of the (reactant) for the reaction and a description of the reaction that is being carried out on that substrate.reaction that is being carried out on that substrate.
• The names usually end with The names usually end with -ase-ase..
• Example: Example: succinate dehydrogenasesuccinate dehydrogenase
CH2CH2C
O
HO C
O
OH
FAD
succinatedehydrogenase
FADH2
succinic acid
CCC
O
HO
C
O
OH
fumaric acid
H
H
CH2CH2C
O
HO C
O
OH
FAD
succinatedehydrogenase
FADH2
succinic acid
CCC
O
HO
C
O
OH
fumaric acid
H
H
6969
Question (Clicker)Question (Clicker)
What class of reaction is the alchohol dehydrogenase What class of reaction is the alchohol dehydrogenase reaction?reaction?
A)A) HydrolysisHydrolysis
B)B) DecarboxylationDecarboxylation
C)C) Oxidation/reductionOxidation/reduction
D)D) Acid/baseAcid/base
E)E) HydrationHydration
CH2CH2C
O
HO C
O
OH
FAD
succinatedehydrogenase
FADH2
succinic acid
CCC
O
HO
C
O
OH
fumaric acid
H
H
CH2CH2C
O
HO C
O
OH
FAD
succinatedehydrogenase
FADH2
succinic acid
CCC
O
HO
C
O
OH
fumaric acid
H
H
7070
Oxidation and Reduction (Unit 4)Oxidation and Reduction (Unit 4)
The reaction equation on the previous slide also illustrates The reaction equation on the previous slide also illustrates another shorthand method of writing equations, which used another shorthand method of writing equations, which used multiple reaction arrows.multiple reaction arrows.
• The longhand form of this reaction equation isThe longhand form of this reaction equation is
HO C
O
C C
H H
C
OH H
OH
succinic acid(saturated)
HO C
O
C C
H
C
O
OH
fumaric acid(unsaturated)
FAD FADH2 H
H
HO C
O
C C
H H
C
OH H
OH
succinic acid(saturated)
FAD HO C
O
C C
H
C
O
OH
fumaric acid(unsaturated)
FADH2+ +
7171
EnzymesEnzymes
The common names for enzymes often describe the The common names for enzymes often describe the substratesubstrate (reactant) for the reaction and a description of the (reactant) for the reaction and a description of the reaction that is being carried out on that substrate.reaction that is being carried out on that substrate.
• The names usually end with The names usually end with -ase-ase..
• Example: Example: succinate dehydrogenasesuccinate dehydrogenase
CCC
O
HO
C
O
OH
fumaric acid
H
H
CCH2C
O
HO C
O
OH
L-malic acid
fumarase
+ H2O
OH
H
CCC
O
HO
C
O
OH
fumaric acid
H
H
CCH2C
O
HO C
O
OH
L-malic acid
fumarase
+ H2O
OH
H
7272
Question (Clicker)Question (Clicker)
What class of reaction is the fumarase reaction? (Unit 8)What class of reaction is the fumarase reaction? (Unit 8)
A)A) HydrolysisHydrolysis
B)B) DecarboxylationDecarboxylation
C)C) Oxidation/reductionOxidation/reduction
D)D) Acid/baseAcid/base
E)E) HydrationHydration
CCC
O
HO
C
O
OH
fumaric acid
H
H
CCH2C
O
HO C
O
OH
L-malic acid
fumarase
+ H2O
OH
H
CCC
O
HO
C
O
OH
fumaric acid
H
H
CCH2C
O
HO C
O
OH
L-malic acid
fumarase
+ H2O
OH
H
7373
Reactions Involving Water (Unit 4)Reactions Involving Water (Unit 4)
HydrationHydration• In the In the hydration hydration reaction water is also split, but instead of reaction water is also split, but instead of
being used to split another molecule, it is added to another being used to split another molecule, it is added to another molecule to produce a single product.molecule to produce a single product.
• The water it is added to either an alkene or alkyne:The water it is added to either an alkene or alkyne:
• The hydration of an alkene produces an alcohol.The hydration of an alkene produces an alcohol.
C CH
H H
H + H OHacid
catalyst
C CH
H H
H
H OH
ethene(an alkene)
ethanol(an alcohol)
7474
EnzymesEnzymes
SpecificitySpecificity• Absolute spectificityAbsolute spectificity - enzyme only accepts one specific - enzyme only accepts one specific
substrate.substrate.• Relative specificityRelative specificity - enzyme accepts a range of related - enzyme accepts a range of related
substrates.substrates.
R CH2 OH
NAD+ NADH + H+
CH3 C H
O
ethanol ethanal(acetaldehyde)
alcohol dehydrogenaseenzyme
alcohol aldehyde
R CH2 OH
NAD+ NADH + H+
CH3 C H
O
ethanol ethanal(acetaldehyde)
alcohol dehydrogenaseenzyme
alcohol aldehyde
7575
EnzymesEnzymes
SpecificitySpecificity• Stereospecific specificityStereospecific specificity - enzyme only reacts with or - enzyme only reacts with or
produces one specific stereoisomerproduces one specific stereoisomer
CH2CH2C
O
HO C
O
OH
FAD
succinatedehydrogenase
FADH2
succinic acid
CCC
O
HO
C
O
OH
fumaric acid
H
HCC
C
O
HO C
O
OH
maleic acid
HH
+
trans cis
CH2CH2C
O
HO C
O
OH
FAD
succinatedehydrogenase
FADH2
succinic acid
CCC
O
HO
C
O
OH
fumaric acid
H
HCC
C
O
HO C
O
OH
maleic acid
HH
+
trans cis
CCC
O
HO
C
O
OH
fumaric acid
H
H
CCH2C
O
HO C
O
OH
L-malic acid
fumarase
+ H2O
OH
H
CCH2C
O
HO C
O
OH
D-malic acid
H
OH
+CCC
O
HO
C
O
OH
fumaric acid
H
H
CCH2C
O
HO C
O
OH
L-malic acid
fumarase
+ H2O
OH
H
CCH2C
O
HO C
O
OH
D-malic acid
H
OH
+
7676
EnzymesEnzymes
SpecificitySpecificity• AbsoluteAbsolute• RelativeRelative• StereospecificStereospecific
7777
EnzymesEnzymes
CatalysisCatalysis• As catalysis, enzyme have no effect on the change in free As catalysis, enzyme have no effect on the change in free
energy, energy, ΔΔG,G, for a reaction for a reaction• Ezymes speed up reactions by decreasing the activation Ezymes speed up reactions by decreasing the activation
energy, energy, EEactact..• Enzymes do this by binding the substrates and by directing the Enzymes do this by binding the substrates and by directing the
reaction reaction
7878
Free Energy and Reaction Rates (Unit 4)Free Energy and Reaction Rates (Unit 4)
There is a third way to speed up the reaction rate and that is There is a third way to speed up the reaction rate and that is to lower the height of the hill.to lower the height of the hill.
• This is done using This is done using catalystscatalysts, which provide an alternative , which provide an alternative pathway over the hill for the reactants.pathway over the hill for the reactants.
FreeFreeEnergyEnergy
(G)(G)
FreeFreeEnergyEnergy
(G)(G)
Progress ofProgress ofreactionreaction
Progress ofProgress ofreactionreaction
Α Α → → BBΑ Α → → BB
AAAA
ΒΒΒΒ
ΔΔGG < 0 < 0spontaneousspontaneous
ΔΔGG < 0 < 0spontaneousspontaneous
EEactact > 0 > 0without catalystwithout catalyst
--with catalystwith catalyst
EEactact > 0 > 0without catalystwithout catalyst
--with catalystwith catalyst
7979
EnzymesEnzymes
CatalysisCatalysis• The location on the enzyme where the substrate binds and The location on the enzyme where the substrate binds and
the reaction occurs is called the the reaction occurs is called the active siteactive site..• Back in Unit 4 we saw a specific example of this with the Back in Unit 4 we saw a specific example of this with the
hexokinase reaction hexokinase reaction
Explore the enzyme hexokinaseExplore the enzyme hexokinase
8080
EnzymesEnzymes
Cofactors and CoenzymesCofactors and Coenzymes• Sometimes enzymes need some help with catalzying the Sometimes enzymes need some help with catalzying the
reactions.reactions.• Cofactors are non-protein components of an enzymeCofactors are non-protein components of an enzyme• Metal ionsMetal ions• Organic molecules (Coenzymes)Organic molecules (Coenzymes)
• Many of the coenzymes are derived from the vitamins that Many of the coenzymes are derived from the vitamins that we take in in our diet.we take in in our diet.
8181
EnzymesEnzymes
8282
EnzymesEnzymes
pHpH and Temperature and Temperature• Enyzme activity is often critically dependent on the Enyzme activity is often critically dependent on the pHpH and and
temperature.temperature.
8383
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
Michaelis-Meten enzymes behave according to a model Michaelis-Meten enzymes behave according to a model proposed in the early 1900’s by Michaelis and Menten.proposed in the early 1900’s by Michaelis and Menten.
• E = enyzmeE = enyzme• S = substrateS = substrate• ES = enzyme-substrate complexES = enzyme-substrate complex• P = productP = product
8484
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
Raymond describes an analogy of reaching into a box for an Raymond describes an analogy of reaching into a box for an orgrange, pulling one out, and peeling it.orgrange, pulling one out, and peeling it.
• The Michaelis-Menten model is characterized by two The Michaelis-Menten model is characterized by two parameters.parameters.• KKMM (The Michaelis-Menten constant), which is related to the strength (The Michaelis-Menten constant), which is related to the strength
of the substrate binding.of the substrate binding.• VVmaxmax (The maximum velocity), which corresponds to the maximum (The maximum velocity), which corresponds to the maximum
rate that the enzyme-substrate complex forms product.rate that the enzyme-substrate complex forms product.
KKMMKKMM VVmaxmaxVVmaxmax
8585
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
Enzyme InhibitionEnzyme Inhibition• Can be a normal Can be a normal
event used by the cell event used by the cell to control enzyme to control enzyme activity.activity.
• Can also be exploited Can also be exploited in the design of drugs.in the design of drugs.• ExampleExample, the , the
irreversible irreversible inhibitioninhibition of COX of COX enzymes by aspirinenzymes by aspirin
8686
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
Enzyme Inhibition can also be ReversibleEnzyme Inhibition can also be Reversible• Competitive inhibitionCompetitive inhibition• The inhibitor competes with the substrate for the active siteThe inhibitor competes with the substrate for the active site
KKMMKKMM VVmaxmaxVVmaxmax
Competitive inhibitionCompetitive inhibitionaffect affect
KKMM but not V but not Vmaxmax
Competitive inhibitionCompetitive inhibitionaffect affect
KKMM but not V but not Vmaxmax
8787
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
Some drugs are competitive inhibitors of enzymesSome drugs are competitive inhibitors of enzymes• Example: the anti-HIV drug AZTExample: the anti-HIV drug AZT
• The AZT inhibits the enzyme The AZT inhibits the enzyme reverse trascriptase enzymereverse trascriptase enzyme, , which the HIV virus uses to converts it RNA to DNA. The which the HIV virus uses to converts it RNA to DNA. The drug mimics the normal substrate for this enzyme, dTTP.drug mimics the normal substrate for this enzyme, dTTP.
• This drug targets the activity of the HIV virus because This drug targets the activity of the HIV virus because humans do not use a reverse transcriptase enzyme.humans do not use a reverse transcriptase enzyme.
8888
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
Some drugs are competitive inhibitors of enzymesSome drugs are competitive inhibitors of enzymes• Example: the bacterial drug sufanilamide (a sulfa drug).Example: the bacterial drug sufanilamide (a sulfa drug).
• The sufanilamide inhibits the an enzyme that bacteria use The sufanilamide inhibits the an enzyme that bacteria use to synthesize the coenzyme folate. The drug mimics the to synthesize the coenzyme folate. The drug mimics the normal substrate for this enzyme, normal substrate for this enzyme, pp-aminobenoate.-aminobenoate.
8989
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
• This drug targets the activity of bacteria because humans This drug targets the activity of bacteria because humans do not synthesize their own folate, getting it instead from do not synthesize their own folate, getting it instead from their diet.their diet.
FolateFolateFolateFolate
9090
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
Enzyme Inhibition can also be ReversibleEnzyme Inhibition can also be Reversible• Noncompetitive inhibitionNoncompetitive inhibition• The inhibitor binds at a different site thatn the substrate.The inhibitor binds at a different site thatn the substrate.
KKMMKKMM VVmaxmaxVVmaxmax
Noncompetitive inhibitionNoncompetitive inhibitionaffects affects
VVmax max but not Kbut not KMM
Noncompetitive inhibitionNoncompetitive inhibitionaffects affects
VVmax max but not Kbut not KMM
9191
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
Noncompetitive inhibition is often used to regulate Noncompetitive inhibition is often used to regulate biosynthetic pathways by a mechanism called biosynthetic pathways by a mechanism called feedback feedback inhibitioninhibition..• The end product of the pathway binds to a site on an The end product of the pathway binds to a site on an
enzyme used earlier in the pathway, and turns it off.enzyme used earlier in the pathway, and turns it off.
9292
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
Enzymes that are inhibited by a substance binding to a site Enzymes that are inhibited by a substance binding to a site other than the active site are called other than the active site are called allosteric enzymesallosteric enzymes..• The enzymes that are regulated by noncompetive inhibition The enzymes that are regulated by noncompetive inhibition
in feedback inhibition are examples of allosteric enzyme. in feedback inhibition are examples of allosteric enzyme.• The substance that inhibits the enzyme in this way is called The substance that inhibits the enzyme in this way is called
a a negative effectornegative effector..
Some allosteric enzymes are activated instead of inhibited by Some allosteric enzymes are activated instead of inhibited by as substance binding at their allosteric site.as substance binding at their allosteric site.• These substances are called These substances are called positive effectorspositive effectors..
9393
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
Some enzymes are controlled by covalent modifications to Some enzymes are controlled by covalent modifications to their structure.their structure.• In some cases the modifications are reversible, such as In some cases the modifications are reversible, such as
placing a phosphate on an enzyme to turn it on, and then placing a phosphate on an enzyme to turn it on, and then taking the phosphate off to turn it off again.taking the phosphate off to turn it off again.
9494
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
Some enzymes are controlled by covalent modifications to Some enzymes are controlled by covalent modifications to their structure.their structure.• Example: Glycogen phosphorylase, which is the enzyme Example: Glycogen phosphorylase, which is the enzyme
that breaks down the polysaccharide glycogen.that breaks down the polysaccharide glycogen.• The phosphorylation/dephosphorylation of this enzyme is The phosphorylation/dephosphorylation of this enzyme is
under hormonal control.under hormonal control.
9595
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
Some enzymes are controlled by covalent modifications to Some enzymes are controlled by covalent modifications to their structuretheir structure• In other cases the covalent modification is irreversible.In other cases the covalent modification is irreversible.
9696
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
Some enzymes are controlled by covalent modifications to Some enzymes are controlled by covalent modifications to their structuretheir structure• Example: the digestive enzymes trypsin and chymotrypsin, Example: the digestive enzymes trypsin and chymotrypsin,
which are used to break down proteins in the small which are used to break down proteins in the small intestine are synthesized in the pancreas in an inactive intestine are synthesized in the pancreas in an inactive form called trypsinogen and chymotrypsinogen, form called trypsinogen and chymotrypsinogen, respectively.respectively.
• They are transported in this inactive form to the small They are transported in this inactive form to the small intestine, there are activated by removing parts of their intestine, there are activated by removing parts of their amino acids sequence.amino acids sequence.
9797
Control of Enzyme-Catalyzed ReactionsControl of Enzyme-Catalyzed Reactions
In a clinical setting, the presence of enzymes in blood is often In a clinical setting, the presence of enzymes in blood is often used to diagnose tissue damage that is related to various used to diagnose tissue damage that is related to various diseases.diseases.
The EndThe End
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