chapter 22 & 23 proteins and enzymes chemistry b11
TRANSCRIPT
Chapter 22 & 23
Proteins and Enzymes
Chemistry B11
Function of proteins
Function of proteins
- 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 account for 50% of the dry weight of the human body.
Proteins
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.
• 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.
side chain
H2N— C —COOH H3N— C —COO−
Amino acids
+Zwitterion
α-carbon
H H
Ionized form (Salt)
R R
This form never exist in nature.
Amino acids
H │
H3N—C —COO−
│ H glycine
CH3 │
H3N—C —COO−
│ H alanine
+
+
Only difference: containing a different side group (R) for each.
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 only 20 different amino acids in the proteins in humans.
There are many amino acids.
Amino acids
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
NH3+
COO-
NH3+
COO-
NH3+
COO-
NH3+
COO-
NH3+
COO-S
NH3+
COO-
NH H
COO-
NH3+
COO-
NH
COO-
NH3+
Alanine (Ala, A)
Glycine (Gly, G)
Isoleucine (Ile, I)
Leucine (Leu, L)
Methionine (Met, M)
Phenylalanine (Phe, F)
Proline (Pro, P)
Tryptophan (Trp, W)
Valine (Val, V)
NH3+
COO-
HS
NH3+
COO-
HO
Cysteine (Cys, C)
Tyrosine (Tyr, Y)
NH3+
COO-H2N
O
NH3+
COO-
H2N
O
NH3+
COO-
HO
NH3+
COO-OH
Asparagine (Asn, N)
Glutamine (Gln, Q)
Serine (Ser, S)
Threonine (Thr, T)
Polar amino acids
NH3+
COO--O
O
NH3+
COO--O
O NH3+
COO-
NH
H2N
NH2+
NH3+
COO-
N
NH
NH3+
COO-H3N
Glutamic acid (Glu, E)
Aspartic acid (Asp, D)
Histidine (His, H)
Lysine (Lys, K)
Arginine (Arg, R)
+
Acidic and basic amino acids
Fischer projections
All of the α-amino acids are chiral (except glycine)
Four different groups are attached to central carbon (α-carbon).
H NH3+
COO-
CH3
+H3N H
COO-
CH3
D-Alanine L-Alanine
(Fischer projections)
H NH3+
COO-
CH3
+H3N H
COO-
CH3
D-Alanine L-Alanine
(Fischer projections)
CH2SH CH2SH
D-cysteine L-cysteine
L isomers is found in the body proteins and in nature.
Ionization and pH
pH: 6 to 7 Isoelectric point (pI)
Positive charges = Negative chargesNo net charge (Neutral) - Zwitterion
pH: 3 or less -COO- acts as a base and accepts an H+
+
RH3N-CH-C-O
-O
+ H3O+ +
RH3N-CH-C-OH
O+H2O
pH: 10 or higher -NH3+ acts as an acid and loses an H+
+
RH3N-CH-C-O
-O
+ OH-
RH2N-CH-C-O
-O
+H2O
+
RH3N-CH-C-O
-O
+ OH-
RH2N-CH-C-O
-O
+H2O
-
Ionization and pH
The net charge on an amino acid depends on the pH of the solution in which it is dissolved.
pH 2.0 pH 5.0 - 6.0 pH 10.0Net charge +1 Net charge 0 Net charge -1
+
RH3N-CH-C-O
-O+
RH3N-CH-C-OH
O
RH2N-CH-C-O
-OOH-
H3O+
OH-
H3O+
6.015.41
5.655.976.026.025.745.486.485.685.87
5.895.97
pI
valinetryptophan
threonineserineprolinephenylalaninemethionineleucineisoleucineglycineglutamine
asparaginealanine
Nonpolar &polar side chains
10.76
2.77
5.073.22
7.599.74
5.66
pI
tyrosine
lysinehistidine
glutamic acidcysteine
aspartic acid
arginine
AcidicSide Chains
BasicSide Chains pI
Ionization and pH
Each amino acid has a fixed and constant pI.
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.
Peptide
O
O-H3N
CH3H3N O-
CH2OH
O
H3NN
CH3
O CH2OH
O
O-
H
H2O+
Alanine (Ala) Serine (Ser)
++
+
peptide bond
Alanylserine (Ala-Ser)
+
(amide bond)
•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.
Peptide
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
OH
NH O
HN
COO-
O-
OC6H5O
+
C-terminalamino acid
N-terminalamino acid
Ser-Phe-Asp
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.
H3N-CH-C-NH-CH2-C-NH-CH-C-O
CH3 CH2OH
O O O
From alaninealanyl
From glycineglycyl
From serineserine
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.
Ala─Leu─Cys─Met
+
CH3
S
CH2
CH2
SH
CH2
CH3
CH3CH
CH O
O-CCH
H
N
O
CCH
H
N
O
CCH
H
N
O
C
CH3
CHH3N
+
Cysteine
The -SH (sulfhydryl) group of cysteine is easily oxidized
to an -S-S- (disulfide).
+
CH2
H3N-CH-COO-
SH
oxidation
reduction
+
CH2
H3N-CH-COO-
S
+H3N-CH-COO
-CH2
S
CysteineCystine
2
a disulfidebond
Primary Structure of proteins
Chain A
CO
O-
NH3+ NH3
+
CO
O-
Chain B
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)).
- Chain A has 21 amino acids and
chain B has 30 amino acids.
- Genetic engineers can produce it for treatment of diabetes.
Secondary Structure of proteins
Describes the way the amino acids next to or near to each otheralong 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
O H
• 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.
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
α-keratin: hair, wool, skin, nails, and bone
- Have long, thin shape.
- Involve in the structure of cells and tissues.
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.
• Is stabilized by the same interactions found in tertiary structures (between side chains).
• Hemoglobin consists of four polypeptide chains as subunits.
• Is a globular protein and transports oxygen in blood (four molecules of O2).
chain
chain
α chain
α chain
Hemoglobin
Summary of protein Structure
Summary of protein Structure
Denaturation
Active protein
Denatured 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.
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
Eact
Eact
- Like a catalyst, they increase the rate of the reactions (biological reactions).
- Lower the activation energy for the reaction.
2HIH2 + I2 H…H
I … I
… …
- Less energy is required to convert reactants to products.
- But, they are not changed at the end of the reaction.
- They are made of proteins.
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
Maximum activity
Enzyme concentration ↑ Rate of reaction ↑
Substrate concentration ↑ First: Rate of reaction ↑
End: Rate of reaction reachesto its maximum: all of the enzymesare combined with substrates.
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.
- 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.
Inhibitor
Site
Enzyme cofactors
protein
protein
protein
Metal ion
Organicmolecules
(coenzyme)
Simple enzyme
Enzyme + Cofactor
Enzyme + Cofactor
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
Water-soluble vitamins: have a polar group (-OH, -COOH, or …)
Vitamins are organic molecules that must be obtained from the diet.(our body cannot make them)
Fat-soluble vitamins: have a nonpolar group (alkyl, aromatic, or …)
- They are not stored in the body (must be taken).
- They can be easily destroyed by heat, oxygen, and ultraviolet light (need care).
- 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.