1. Amino Acids, Proteins, and Enzymes
Chemistry 203
Chapter 21
Amino Acids, Proteins, and Enzymes

2. Fibrinogen helps blood clotting
Function of proteins
Fibrinogen helps blood clotting

3. Function of proteins

4. 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.

5. Proteins Fibrous proteins: Globular proteins:
100,000 different proteins in human body
Fibrous proteins:
Insoluble in water – used for structural purposes (Keratin & Collagen).
Globular proteins:
More or less soluble in water – used for nonstructural purposes.

6. 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.
side chain
H2N— C —COOH H3N— C —COO− R R
Zwitterion + H H
α-carbon
Ionized form (Salt)
This form never exist in nature.

7. H Amino acids │ H3N—C —COO− + H glycine CH3 H alanine
Only difference: containing a different side chain (R) for each. H │
H3N—C —COO−
H glycine
CH3
H alanine +

8. Amino acids Amino acids are classified as:
Nonpolar (Neutral) amino acids (hydrophobic) with hydrocarbon (alkyl or aromatic) sides chains.
Polar (Neutral) 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.

9. 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).

10. Nonpolar (Neutral) amino acids

11. Polar (Neutral) amino acids

12. Acidic and basic amino acids

13. All of the α-amino acids are chiral (except glycine)
Fischer projections
All of the α-amino acids are chiral (except glycine)
Four different groups are attached to central carbon (α-carbon).
CH2SH
D-cysteine
L-cysteine
L isomers is found in the body proteins and in nature.

14. Ionization and pH - pH: 6 to 7 Isoelectric point (pI)
Positive charges = Negative charges
No net charge (Neutral) - Zwitterion
pH: 3 or less
-COO- acts as a base and accepts an H+
pH: 10 or higher
-NH3+ acts as an acid and loses an H+ -

15. Ionization and pH The net charge on an amino acid depends on the
pH of the solution in which it is dissolved.

16. Ionization and pH
Each amino acid has a fixed and constant pI.

17. When an amide links two amino acids (Peptide bond).
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.
(amide bond)

18. 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 40 amino acids joined by peptide bonds.

19. Naming of peptides
C-terminal amino acid: the amino acid at the end of the chain
having the free -COO- group (always written at the left).
N-terminal amino acid: the amino acid at the end of the chain
having the free -NH3+ group (always written at the right).

20. - Begin from the N terminal.
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 + -
From alanine
alanyl
From glycine
glycyl
From serine
serine
Alanylglycylserine
(Ala-Gly-Ser)

21. Biologically Active Peptides
- Enkephalins, pentapeptides made in the brain, act as pain killers and sedatives by binding to pain receptors.
- Addictive drugs morphine and heroin bind to these same pain receptors, thus producing a similar physiological response, though longer lasting.
- Enkephalins belong to the family of polypeptides called endorphins (16-31 amino acids), which are known for their pain reducing and mood enhancing effects.

22. Biologically Active Peptides
Enkephalins:
Met-enkephalin:
It contains a C-terminal methionine.
Leu-enkephalin:
It contains a C-terminal leucine.

23. Biologically Active Peptides
Oxytocin and vasopressin are cyclic nonapeptide hormones, which have identical sequences except for two amino acids.

24. Biologically Active Peptides
Oxytocin stimulates the contraction of uterine muscles, and signals for milk production; it is often used to induce labor.
Vasopressin, antidiuretic hormone (ADH) targets the kidneys and helps to limit urine production to keep body fluids up during dehydration.

25. Structure of proteins 1. Primary structure 2. Secondary structure
3. Tertiary structure
4. Quaternary structure

26. 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. C H 3 C H S 3 C H C H S H C H 3 2 C H O C H O C H O C H O + 3 + 2 2 H N C H C N C H C N C H C N C H C O - 3 H H H
Ala─Leu─Cys─Met

27. Cysteine The -SH (sulfhydryl) group of cysteine is easily oxidized
to an -S-S- (disulfide).

28. Primary Structure of proteins
NH3+
NH3+
Primary Structure of proteins
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. O C O- O C O-
Chain A
Chain B

29. 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.

30. 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

31. 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

32. 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).

33. 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-

34. Tertiary Structure
Disulfide (-S-S-)
(2) salt bridge (acid-base)
(3) Hydrophilic (polar)
(4) hydrophobic (nonpolar)
(5) Hydrogen bond

35. Tertiary Structure Shorthand symbols on a protein Ribbon diagram:
Lysozyme (an enzyme)

36. Globular proteins Myoglobin Have compact, spherical shape.
Almost soluble in water.
- 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).

37. Have long, thin shape and insoluble in water.
Fibrous proteins
Have long, thin shape and insoluble in water.
- Involve in the structure of cells and tissues.
α-keratin: skin, nail, hair, and bone
Superhelix:
Collagen
-keratin: feathers of birds
Large amount of -pleated sheet

38. α-keratin: hair, wool, skin, and nails
Fibrous proteins
α-keratin: hair, wool, skin, and nails
- They are made of two mainly a-helix chains coiled
around each other in a superhelix (supercoil).
- These coils wind around other coils making
larger and stronger structures (like hair).
- α-helix chains bond together by disulfide bond (-S-S-)
- More disulfide bonds, more rigid materials
(horns & nails).
Collagen

39. Quaternary Structure Hemoglobin
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).
CO is poisonous because it binds 200 times more strongly to the Fe2+ than does O2 (Cells can die from lack of O2).
α chain
 chain
 chain
α chain
Hemoglobin

40. Conjugated Proteins
They are composed of a protein unit and a nonprotein molecule.
Myoglobin & Hemoglobin
Heme: a complex organic compound containing the Fe2+.

41. Sickle Cell Hemoglobin
Sickle cell anemia is a disease where a single amino acid of both β subunits is changed from glutamic acid to valine.
- A genetic mutation in the DNA sequence that is responsible for synthesis of hemoglobin.
- Red blood cells containing these mutated hemoglobin units become elongated and crescent (sickle) shaped (more fragile).
- These red blood cells will rupture capillaries,
causing pain and inflammation, leading
to organ damage, and eventually
a painful death.

42. Summary of protein Structure

43. Summary of protein Structure

44. Denaturation - Is a process of destroying a protein
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.
Ovalbumin

45. 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

46. Enzymes

47. Enzyme H…H H2 + I2   2HI … I … I
- Like a catalyst, they increase the rate of biological reactions (106 to 1012 times faster).
- But, they are not changed at the end of the reaction.
Eact
- They are made of proteins.
- Lower the activation energy for the reaction.
 2HI
H2 + I2 
H…H
I … I …
- Less energy is required to convert reactants to products.

48. Most of enzymes are globular proteins (water soluble).
Proteins are not the only biological catalysts.
Most of enzymes are specific.
(Trypsin: cleaves the peptide bonds of proteins)
Some enzymes are localized according to need.
(digestive enzymes: stomach)

49. Names of Enzymes with the suffix « -ase ».
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.

50. Enzyme
- Substrate: the compound or compounds whose reaction an enzyme catalyzes.
- Active site: the specific portion of the enzyme to which a substrate binds during reaction.

51. 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
Complex (ES).
Forming and releasing products.
E + S ES E + P
Enzyme: globular protein

52. 1. 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

53. 2. 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.

54. 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

55. 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: 37°C or body temperature.

56. pH Optimum pH: is 7.4 in our body.
Lower or higher pH can change the shape of enzyme.
(active site change 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.

57. Substrate and enzyme concentration
Rate of reaction ↑
Substrate concentration ↑
First: Rate of reaction ↑
End: Rate of reaction reaches
to its maximum: all of the enzymes
are combined with substrates.
Maximum activity

58. Enzyme inhibition
Inhibitors cause enzymes to lose catalytic activity.
Competitive inhibitor
Noncompetitive inhibitor

59. 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.

60. 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 (change tertiary structure).
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

61. Competitive and Noncompetitive Inhibitor

62. Enzyme cofactors Metal ions: bond to side chains. (coenzyme)
protein
Metal ion
Organic
molecules
(coenzyme)
Simple enzyme (apoenzyme)
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.

63. Enzyme cofactors Enzyme and cofactors work together.
Catalyze reactions properly.

64. 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.

65. Zymogens (Proenzymes)
Zymogen (Proenzyme): an inactive enzyme that becomes an active
enzyme after a chemical change (remove or change some polypeptides).
Trypsinogen (inactive enzyme)
Trypsin (active enzyme)
Pancreas
Small intestine
Digestive enzyme (hydrolyzes the peptide bonds of proteins)

66. - Most of enzymes are in cells.
Enzymes in medicine
- Most of enzymes are in cells.
Small amounts of them are in body fluids (blood, urine,…).
Level of enzyme activity can be monitored.
Find some diseases

67. Enzymes in medicine
Certain enzymes are present in higher amounts in particular cells.
If these cells are damaged or die, the enzymes are released into the bloodstream and can be detected.
Enzyme
Condition
Creatine phosphokinase
Heart attack
Alkaline phosphatase
Liver or bone disease
Acid phosphatase
Prostate cancer

68. Enzymes in medicine Inhibitors can be useful drugs.
Penicillin inhibits the enzyme that forms cell walls of bacteria, destroying the bacterium.
ACE (angiotensin-converting enzyme) causes blood vessels to narrow, increasing blood pressure.
ACE inhibitors are given to those with high blood pressure to prevent ACE’s synthesis from it’s zymogen.
HIV protease is an essential enzyme that allows the virus to make copies of itself.
HIV protease inhibitors interfere with this copying, decreasing the virus population in the patient.