Transcript Chemistry B11 Chapter 22 & 23 Proteins and Enzymes Function of proteins.

Chemistry B11
Chapter 22 & 23
Proteins and Enzymes
Function of proteins
Function of proteins
Proteins
- Proteins account for 50% of the dry weight of the human body.
- Unlike lipids and carbohydrates, proteins are not stored, so they
must be consumed daily.
- Current recommended daily intake for adults is 0.8 grams of
protein per kg of body weight (more is needed for children).
- Dietary protein comes from eating meat and milk.
Proteins
100,000 different proteins in human body.
Fibrous proteins:
Insoluble in water – used for structural purposes.
Globular proteins:
More or less soluble in water – used for nonstructural purposes.
Amino acids
•
•
•
•
•
Are the building blocks of proteins.
Contain carboxylic acid and amino groups.
Are ionized in solution (soluble in water).
They are ionic compounds (solids-high melting points).
Contain a different side group (R) for each.
R
side chain
H2N— C —COOH
H
α-carbon
This form never exist in nature.
R
+
H3N— C —COO−
H
Ionized form (Salt)
Zwitterion
Amino acids
Only difference: containing a different side group (R) for each.
H
│
+
H3N—C —COO−
│
H
glycine
CH3
│
+
H3N—C —COO−
│
H
alanine
Amino acids
Amino acids are classified as:
• Nonpolar amino acids
(hydrophobic) with hydrocarbon
(alkyl or aromatic) sides chains.
• Polar amino acids (hydrophilic)
with polar or ionic side chains.
• Acidic amino acids (hydrophilic)
with acidic side chains (-COOH).
• Basic amino acids (hydrophilic)
with –NH2 side chains.
Amino acids
There are many amino acids.
There are only 20 different amino acids in the proteins in humans.
They are called α amino acids.
- Humans cannot synthesize 10 of these 20 amino acids.
(Essential Amino Acids)
- They must be obtained from the diet (almost daily basis).
Nonpolar amino acids
COONH3
+
COONH3
+
Glycine
(Gly, G)
-
+
Isoleucin e
(Ile, I)
-
COO
NH3 +
S
-
COO
NH3 +
Leucin e
(Leu, L)
Meth ion in e
(Met, M)
-
COO
N
H
COO
NH3
COO Phen ylalan ine
(Phe, F)
+
NH3
A lanine
(A la, A)
N
H
H
Prolin e
(Pro, P)
COO- Tryptoph an
(Trp , W)
+
NH3
COO- Valine
(Val, V)
+
NH3
Polar amino acids
-
-
H2 N
COO
O
NH3
As paragine
(As n, N )
+
HS
NH3
O
-
H2 N
COO
NH3
Glutamine
(Gln, Q)
+
HO
NH3
+
HO
Cysteine
(Cys, C)
+
COO- Serine
(Ser, S)
NH +
3
OH
-
COO
COO
Tyrosine
(Tyr, Y)
-
COO
NH3 +
Threon in e
(Thr, T)
Acidic and basic amino acids
-
COO-
O
O
NH3
+
As partic acid
(As p, D )
NH2 +
H2 N
O
-
O
COO-
N
H
NH3 +
COO- Glutamic acid
NH3
+
(Glu, E)
N
N
H
+
H3 N
Arginin e
(Arg, R)
COONH3
+
COONH3 +
Histidine
(His , H)
Lysine
(Lys, K)
Fischer projections
All of the α-amino acids are chiral (except glycine)
Four different groups are attached to central carbon (α-carbon).
-
COO
H
COO-
-
COO
NH3
+
CH3
+
H3N
H
CH3
D-Alani ne
L-Alanine
(Fi s che r proje ctions )
H
NH3 +
COO+
H3N
CH23SH
CH
H
CH23SH
CH
D-Alani ne
L-Alanine
D-cysteine
L-cysteine
(Fi s che r proje ctions )
L isomers is found in the body proteins and in nature.
Ionization and pH
pH: 6 to 7
Isoelectric point (pI)
O
O
+
charges
-Positive charges = Negative
+
H3 N-CH-C-O + OH
H2 N-CH-C-O
H2 O
No net charge
(Neutral) - Zwitterion
R
R
pH: 3 or less
-COO- acts as a base and accepts an H+
O
+
+
H3 N-CH-C-O + H3 O
R
pH: 10 or higher
O
+
H3 N-CH-C-O + OH
R
O
+
H3 N-CH-C-OH + H2 O
R
-NH3+ acts as an acid and loses an H+
O
H2 N-CH-C-O- + H2 O
R
Ionization and pH
The net charge on an amino acid depends on the
pH of the solution in which it is dissolved.
O
+
H3 N-CH-C-OH
R
pH 2.0
Net charge +1
OH
-
H3 O+
O
+
H3 N-CH-C-O
R
pH 5.0 - 6.0
Net charge 0
OH+
H3 O
O
H2 N-CH-C-O
R
pH 10.0
N et ch arge -1
Ionization and pH
Non pol ar &
polar s ide ch ain s pI
alan i ne
6.01
asparagi n e
5.41
5.07
cys tei n e
glu tamin e
5.65
glycin e
5.97
i sol eu cin e
6.02
l eu cin e
6.02
5.74
me th ion in e
ph e nyl alan in e 5.48
prol in e
6.48
s eri n e
5.68
thre on in e
5.87
tyrosi n e
5.66
tryptoph an
5.89
val i ne
5.97
Acidi c
Si de C h ai n s pI
asparti c aci d 2.77
glu tamic acid 3.22
Bas ic
S ide C h ai n s pI
10.76
argi n in e
h is tidin e
7.59
l ys i ne
9.74
Each amino acid has a fixed and constant pI.
Peptide
A dipeptide forms:
• When an amide links two amino acids (Peptide bond).
• Between the COO− of one amino acid and
the NH3 + of the next amino acid.
pe ptide(amide bond)
bon d
CH3
+
H 3N
O-
O
Al an i n e (Ala)
+
+
H 3N
O
OCH2 OH
S e ri n e (S er)
CH3 H
O
+
N
H 3N
O - + H2 O
O
CH2 OH
Al an yl se rin e
(Ala-S e r)
Peptide
•Dipeptide: A molecule containing two amino acids
joined by a peptide bond.
•Tripeptide: A molecule containing three amino
acids joined by peptide bonds.
•Polypeptide: A macromolecule containing many
amino acids joined by peptide bonds.
•Protein: A biological macromolecule containing at
least 30 to 50 amino acids joined by peptide bonds.
Naming of peptides
C-terminal amino acid: the amino acid at the end of the chain
having the free -COO- group.
N-terminal amino acid: the amino acid at the end of the chain
having the free -NH3+ group.
+
H3N
N-te rmin al
ami n o aci d
O
C6 H5
O
H
N
N
OH
O
OH
COOS e r-Ph e -As p
C -te rmi n al
ami n o aci d
Naming of peptides
- Begin from the N terminal.
- Drop “-ine” or “-ic acid” and it is replaced by “-yl”.
- Give the full name of amino acid at the C terminal.
O
O
O
+
-
H3N-CH-C-NH-CH2-C-NH-CH-C-O
CH3
CH2OH
From alanine
alanyl
From glycine
glycyl
From serine
serine
Alanylglycylserine
(Ala-Gly-Ser)
Structure of proteins
1. Primary structure
2. Secondary structure
3. Tertiary structure
4. Quaternary structure
Primary Structure of proteins
- The order of amino acids held together by peptide bonds.
- Each protein in our body has a unique sequence of amino acids.
- The backbone of a protein.
- All bond angles are 120o, giving the protein a zigzag arrangement.
CH3
CH3
+
CH3 O
+
S
CH CH3
SH
CH2
CH O
CH2 O
CH2 O
H3N CH C N CH C N CH C N CH C OH
H
Ala─Leu─Cys─Met
H
Cysteine
The -SH (sulfhydryl) group of cysteine is easily oxidized
to an -S-S- (disulfide).
+
2 H3 N-CH-COO
CH2
SH
Cysteine
oxidation
reduction
+
H3 N-CH-COO
CH2
a disulfide
bon d
S
S
CH2
+
H3 N-CH-COO
Cystine
NH3+
Primary Structure of proteins
NH3+
The primary structure of insulin:
- Is a hormone that regulates the glucose level
in the blood.
- Was the first amino acid order determined.
- Contains of two polypeptide chains linked by
disulfide bonds (formed by side chains (R)).
O
C
O-
- Chain A has 21 amino acids and
chain B has 30 amino acids.
- Genetic engineers can produce it for
treatment of diabetes.
O
C
O-
Chain A
Chain B
Secondary Structure of proteins
Describes the way the amino acids next to or near to each other
along the polypeptide are arranged in space.
1. Alpha helix (α helix)
2. Beta-pleated sheet (-pleated sheet)
3. Triple helix (found in Collagen)
4. Some regions are random arrangements.
Secondary Structure - α-helix
• A section of polypeptide chain coils into a rigid
spiral.
• Held by H bonds between the H of N-H group
and the O of C=O of the fourth amino acid
down the chain (next turn).
• looks like a coiled “telephone cord.”
• All R- groups point outward from the helix.
• Myosin in muscle and α-Keratin in hair
have this arrangement.
H-bond
Secondary Structure - -pleated sheet
• Consists of polypeptide chains (strands) arranged side by side.
• Has hydrogen bonds between the peptide chains.
• Has R groups above and below the sheet (vertical).
• Is typical of fibrous proteins such as silk.
O
H
Secondary Structure – Triple helix (Superhelix)
- Collagen is the most abundant protein.
- Three polypeptide chains (three α-helix) woven together.
- It is found in connective tissues: bone, teeth, blood
vessels, tendons, and cartilage.
- Consists of glycine (33%), proline (22%), alanine (12%),
and smaller amount of hydroxyproline and hydroxylysine.
- High % of glycine allows the chains to lie close to each
other.
- We need vitamin C to form H-bonding (a special enzyme).
Tertiary Structure
The tertiary structure is determined by attractions and repulsions
between the side chains (R) of the amino acids in a polypeptide chain.
Interactions between side
chains of the amino acids
fold a protein into a specific
three-dimensional shape.
-S-S-
Tertiary Structure
(1) Disulfide (-S-S-)
(2) salt bridge (acid-base)
(3) Hydrophilic (polar)
(4) hydrophobic (nonpolar)
(5) Hydrogen bond
Globular proteins
- Have compact, spherical shape.
- Carry out the work of the cells:
Synthesis, transport, and metabolism
Myoglobin
Stores oxygen in muscles.
153 amino acids in a single polypeptide chain (mostly α-helix).
Fibrous proteins
- Have long, thin shape.
- Involve in the structure of cells and tissues.
α-keratin: hair, wool, skin, nails, and bone
Three α-helix bond together by disulfide bond (-S-S-)
-keratin: feathers of birds
Large amount of -pleated sheet
Quaternary Structure
• Occurs when two or more protein
units (polypeptide subunits) combine.
α chain
 chain
• Is stabilized by the same
interactions found in tertiary
structures (between side chains).
• Hemoglobin consists of four
polypeptide chains as subunits.
 chain
• Is a globular protein and transports
oxygen in blood (four molecules of O2).
α chain
Hemoglobin
Summary of protein Structure
Summary of protein Structure
Denaturation
Active protein
- Is a process of destroying a protein
by chemical and physical means.
- We can destroy secondary, tertiary,
or quaternary structure but the primary
structure is not affected.
- Denaturing agents: heat, acids and bases,
organic compounds, heavy metal ions, and
mechanical agitation.
- Some denaturations are reversible,
while others permanently damage the protein.
Denatured protein
Denaturation
•Heat: H bonds, Hydrophobic interactions
•Detergents: H bonds
•Acids and bases: Salt bridges, H bonds.
•Reducing agents: Disulfide bonds
•Heavy metal ions (transition metal ions Pb2+, Hg2+): Disulfide bonds
•Alcohols: H bonds, Hydrophilic interactions
•Agitation: H bonds, Hydrophobic interactions
Enzymes
Enzyme
- Like a catalyst, they increase the rate of the reactions (biological reactions).
- But, they are not changed at the end of the reaction.
- They are made of proteins.
- Lower the activation energy for the reaction.
…
…
H2 + I2 
H…H
I …I
Eact
Eact
 2HI
- Less energy is required to convert reactants to products.
Names of Enzymes
- By replacing the end of the name of reaction or reacting compound
with the suffix « -ase ».
Oxidoreductases: oxidation-reduction reactions (oxidase-reductase).
Transferases: transfer a group between two compounds.
Hydrolases: hydrolysis reactions.
Lyases: add or remove groups involving a double bond without hydrolysis.
Isomerases: rearrange atoms in a molecule to form a isomer.
Ligases: form bonds between molecules.
Enzyme catalyzed reaction
An enzyme catalyzes a reaction by,
• Attaching to a substrate at the
active site (by side chain (R) attractions).
• Forming an enzyme-substrate
(ES) complex.
• Forming and releasing products.
• E+S
ES
E+ P
Enzyme: globular protein
Lock-and-Key model
- Enzyme has a rigid, nonflexible shape.
- An enzyme binds only substrates that
exactly fit the active site.
-The enzyme is analogous to a lock.
- The substrate is the key that fits into the lock
Induced-Fit model
- Enzyme structure is flexible, not rigid.
- Enzyme and substrate adjust the shape
of the active site to bind substrate.
- The range of substrate specificity
increases.
- A different substrate could not induce
these structural changes and no
catalysis would occur.
Factors affecting enzyme activity
Activity of enzyme: how fast an enzyme catalyzes the reaction.
1. Temperature
2. pH
3. Substrate concentration
4. enzyme concentration
5. Enzyme inhibition
Temperature
- Enzymes are very sensitive to temperature.
- At low T, enzyme shows little activity (not an enough amount of energy for
the catalyzed reaction).
- At very high T, enzyme is destroyed (tertiary structure is denatured).
- Optimum temperature: 35°C or body temperature.
pH
- Optimum pH: is 7.4 in our body.
- Lower or higher pH can change the shape of enzyme.
(active site changes and substrate cannot fit in it)
- But optimum pH in stomach is 2.
Stomach enzyme (Pepsin) needs an acidic pH to digest the food.
- Some damages of enzyme are reversible.
Substrate and enzyme concentration
Enzyme concentration ↑
Substrate concentration ↑
Rate of reaction ↑
First: Rate of reaction ↑
End: Rate of reaction reaches
to its maximum: all of the enzymes
are combined with substrates.
Maximum activity
Enzyme inhibition
Inhibitors cause enzymes to lose catalytic activity.
Competitive inhibitor
Noncompetitive inhibitor
Competitive Inhibitor
- Inhibitor has a structure that is so similar to the substrate.
- It competes for the active site on the enzyme.
- Solution: increasing the substrate concentration.
Noncompetitive Inhibitor
- Inhibitor is not similar to the substrate.
Inhibitor
- It does not compete for the active site.
- When it is bonded to enzyme, change the shape
of enzyme (active site) and substrate cannot fit in
the active site.
- Like heavy metal ions (Pb2+, Ag+, or Hg2+) that
bond with –COO-, or –OH groups of amino acid
in an enzyme.
- Penicillin inhibits an enzyme needed for formation
of cell walls in bacteria: infection is stopped.
- Solution: some chemical reagent can remove the
inhibitors.
Site
Enzyme cofactors
Simple enzyme
protein
protein
protein
Metal ion
Organic
molecules
Enzyme + Cofactor
Enzyme + Cofactor
(coenzyme)
Metal ions:
bond to side chains.
obtain from foods.
Fe2+ and Cu2+ are gain or loss electrons in redox reactions.
Zn2+ stabilize amino acid side chain during reactions.
Enzyme cofactors
- Enzyme and cofactors work together.
- Catalyze reactions properly.
Vitamins and Coenzymes
Vitamins are organic molecules that must be obtained from the diet.
(our body cannot make them)
Water-soluble vitamins: have a polar group (-OH, -COOH, or …)
- They are not stored in the body (must be taken).
- They can be easily destroyed by heat, oxygen,
and ultraviolet light (need care).
Fat-soluble vitamins: have a nonpolar group (alkyl, aromatic, or …)
- They are stored in the body (taking too much = toxic).
- A, D, E, and K are not coenzymes, but they are important:
vision, formation of bone, proper blood clotting.