Proteins

1
Proteins

• Module 15

2
Proteins

• Proteins are very large molecules with large
  molecular weights (MW)
• Hemoglobin has a MW 64,000
• They are essential for the growth, maintenance,
  and replacement of body tissue
• The functions of proteins in the body are
• Enzymatic Catalysis Enzymes are proteins that
  catalyze most biochemical reactions
• Transport and Storage Hemoglobin is a protein
  that transports oxygen in the body Ferritin is a
  protein that transports (from the blood plasma to
  the liver) and stores (in the liver) iron in the
  body
• Coordinated Motion Actin and Myosin are
  proteins that provide muscle expansion and
  contraction
• Structural Collagen, Keratin, and other
  proteins are the chief constituents of skin,
  bone, hair, and fingernails
• Immune Protection Antibodies are proteins that
  protect the body from foreign substances called
  antigens and help the body fight diseases
• Hormones Insulin, Oxytocin, and other proteins
  are hormones
• Generation and Transmission of Nerve Impulses
  Receptor proteins mediate the response of nerve
  cells to specific stimuli

3
Amino Acids

• Amino acids are the building blocks of proteins.
• They are composed of an amine and a carboxylic
  acid.
• The amine group (-NH2) is attached to the carbon
  that is attached to the carboxyl group (OC-OH).
  This carbon that is attached to the amine group
  and the carboxyl group is referred to as the a
  carbon, and therefore, the amino acids are called
  a-amino acids.
• Amino acids only vary in structure by the R
  group shown below.

4
The 20 Common Amino Acids
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Classification of Amino Acids

• Of these 20 common amino acids, only 10 can be
  synthesized by the body the other 10 need to be
  obtained from our food and are called essential
  amino acids
• Amino acids are classified according to the R
  group
• Nonpolar R group These amino acids contain a
  nonpolar hydrocarbon chain and are hydrophobic
  (not souble in water)
• Alcohol R group These amino acids contain an
  alcohol (-OH)
• Thiol (Sulfur) R group These amino acids
  contain a sulfur
• Basic R group These amino acids contain an
  amine
• Acidic R group These amino acids contain a
  carboxylic acid
• Aromatic R group These amino acids contain a
  benzene ring
• Amide R group These amino acids contain an
  amide

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Properties of Amino Acids

• The general properties of amino acids are
• They can act as acids (due to the carboxylic acid
  group) and bases (due to the amine group), and
  thus they are excellent buffers
• They are soluble in water
• They have high melting points
• They migrate when an electric field is applied
• Amino acids exist as highly polar ions that are
  called zwitterions (double-ions)
• Zwitterions are ions that have both a negative
  and a positive charge within the same structure

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Amino Acids as Zwitterions

• The zwitterionic form of an amino acid exists at
  a certain pH that is called the isoelectric point
• The isoelectric point is a pH at which the amino
  acid is neutral and does not move when an
  electric field is applied
• Each amino acid has a different isoelectric point
• At pHs lower than the isoelectric point, the
  amino acid is a positive ion
• The amino acid ion will migrate to the negative
  pole when an electric field is applied
• At pHs higher than the isoelectric point, the
  amino acid is a negative ion
• The amino acid ion will migrate to the positive
  pole when an electric field is applied

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Amino Acids Above and Below Their Isoelectric
Points
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An Example of Drawing the Three Amino Acid Ions

• Draw the three amino acid ions (the zwitterion,
  the positive ion, and the negaive ion) of
  glycine.
• The zwitterion (at the isoelectric point) is
  obtained by removing a hydrogen from the OH and
  adding it to the nitrogen of the -NH2, thus
  making the oxygen positive and the nitrogen
  negative
• The positive ion (below the isoelectric point) is
  obtained by adding a hydrogen to the oxygen with
  the positive charge in the zwitterion
• The negative ion (above the isoelectric point) is
  obtained by removing a hydrogen from the nitrogen
  with the negative charge in the zwitterion

10
Peptides

• Peptides are molecules that contain two or more
  amino acids
• The amino acids are held together by a peptide
  bond (i.e. an amide bond)
• Peptides are classified by the number of amino
  acids that are joined together
• Dipeptide 2 amino acids joined together
• Tripeptide 3 amino acids joined together
• Polypeptide many amino acids joined together
• Protein more than 50 amino acids joined together

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Peptides Dipeptides

• A dipeptide contains two amino acids held
  together by a peptide bond
• If two DIFFERENT amino acids react with each
  other, there are two possible products (see below
  for example (reaction of alanine (ala) and
  glycine (gly)))

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An Example of Drawing the Structures of a
Dipeptide

• Draw the structure of the dipeptide val-ala.
• The steps to form val-ala
• Remove the OH from val and a hydrogen from the
  NH2 in ala, thus forming water
• Combine the remaining portions to form the
  dipeptide val-ala

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Peptides Tripeptides

• A tripeptide contains three amino acids, which
  are held together by two peptide bonds
• If three DIFFERENT amino acids react with each
  other, there are six possible products
• For example, if ala, gly, and phe react, the
  products are ala-gly-phe ala-phe-gly
  gly-ala-phe gly-phe-ala phe-ala-gly
  phe-gly-ala

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An Example of Drawing the Structures of a
Tripeptide

• Draw the structure of the dipeptide val-gly-phe.
• The steps to form val-gly-phe
• Remove the OH from val and a hydrogen from the
  NH2 in gly, thus forming water
• Also, remove the OH from gly and a hydrogen from
  the NH2 in phe, thus forming water
• Combine the remaining portions in order, thus
  forming the tripeptide val-gly-phe

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Structures of Proteins

• Proteins are polypeptides with more than 50 amino
  acids joined together
• There are four levels of protein organization or
  structure
• Primary Structure
• Secondary Structure
• Tertiary Structure
• Quaternary Structure

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Primary Structure of Proteins

• The primary structure of a protein is determined
  by the sequence of amino acids
• The sequence of amino acids for the protein,
  insulin, was determined first
• Insulin has 51 amino acids
• The insulin of each species has a slightly
  different sequence of amino acids
• Sometimes substituting one or more amino acids in
  a protein has very little affect on the proteins
  function thus, insulin from animals can be used
  in place of human insulin
• Some sequence differences are
• Human thr-ser-ile for amino acids 8-9-10 and
  thr for amino acid 30
• Hog thr-ser-ile for 8-9-10 and ala for 30
• Sheep ala-gly-val for 8-9-10 and ala for 30
• Even though sometimes substituting one or more
  amino acids in a protein has very little affect
  on the proteins function, like in insulin,
  sometimes substituting one or more amino acids in
  a protein has a large affect on the proteins
  function
• Hemoglobin, the protein that carries oxygen in
  red blood cells, has 574 amino acids
• Sickle cell anemia, a serious blood disorder, is
  caused by substituting one amino acid (glutamic
  acid) for another (valine) in hemoglobin
• Normal Hemoglobin thr-pro-glu-glu-lys-ala for
  amino acids 4-5-6-7-8-9
• Sickle Cell Hemoglobin thr-pro-val-glu-lys-ala
  for amino acids 4-5-6-7-8-9

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Secondary Structure of Proteins

• The secondary structure of proteins is the
  folding or aligning of proteins in a repeating
  pattern
• The secondary structure is caused by hydrogen
  bonding either
• within a protein molecule, which is called
  intramolecular hydrogen bonding, which causes the
  protein to coil itself like a telephone cord,
  which is called an alpha (a) helix
• OR
• between several proteins molecules, which is
  called intermolecular hydrogen bonding, which
  forms a ß-pleated sheet
• Some examples of the secondary structures of
  proteins
• The tough fibers of wool, skin, and nails are
  made up of fibrous proteins that are called alpha
  keratins, which consist of three to seven alpha
  helixes coiled up tightly like a rope
• Collagen is a fibrous protein that is made up of
  a triple helix that is wound like a coil

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A Diagram of the Secondary Structure of Proteins
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Tertiary Structure of Proteins

• The tertiary structure of a protein is its
  three-dimensional structure
• The tertiary structure is maintained by the
  interactions of
• Covalent Cross Linkages or Disulfide Linkages,
  which are formed when two cysteine molecules
  undergo oxidation (-S-H H-S- ? -S-S- (the
  disulfide linkage is the bond between the two
  sulfur molecules)
• Hydrogen Bonding, which is the attraction between
  hydrogen, which has a partially positive charge,
  and oxygen, which has a partially negative charge
• Salt Bridges, which occur between positive and
  negative ions that result from the R groups of
  amino acids having a charge
• Hydrophobic Interactions, which occur between the
  nonpolar R groups of amino acids
• The protein folds to shield these nonpolar R
  groups from the solvent water molecules since
  these nonpolar R groups are repulsed by the
  solvent

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A Diagram of the Tertiary Structure of Proteins
21
Quaternary Structure of Proteins

• The quaternary structure of proteins is the way
  that proteins with more than one polypeptide
  chain fit together
• It is maintained by the same linkages that
  maintain the tertiary structure
• The quaternary structure gives the protein
  molecule its characteristic shape

22
Denaturation of Proteins

• Denaturation of a protein occurs when it loses
  its biological activity
• Denaturation agents are physical or chemical
  agents that affect the secondary, tertiary, or
  quaternary structure of a protein, thus
  denaturing it
• Some denaturation agents are
• Heat and ultraviolet radiation, which break
  hydrogen bonding
• Heat denatures the protein in bacteria on
  surgical instruments
• Alcohol and other organic solvents, which
  coagulate proteins
• A 70 isopropyl alcohol solution penetrates and
  destroys bacteria before an injection in the arm
  is applied
• Reducing agents, which break disulfide linkages
• Permanents use reducing agents to break up
  keratin, the protein that is in human hair
• pH changes, which affect salt bridges and
  hydrogen bonding
• Stomach acid (0.5 HCl) denatures proteins and
  cleaves peptide linkages, which destroys the
  primary structure
• Heavy metals (Ag, Pb2, Hg2, etc.), which react
  with disulfide bonds
• A 1 AgNO3 solution destroys the bacteria that
  causes gonorrhea when placed in a newborns eyes
• The protein can be restored to its original shape
  and biological activity by carefully reversing
  any MILD conditions that caused denaturation
• If the conditions that caused denaturation where
  VERY STRONG, however, the protein cannot be
  restored, and it precipitate out of solution

23
Hydrolysis of Proteins

• A protein is hydrolyzed in the presence of an
  acid or an enzyme (trypsin, pepsin, etc.)
• Proteins are first hydrolyzed to smaller peptides
  and then to amino acids
• Proteins ? Peptides ? Amino Acids