Protein: Amino Acids

- Protein
o From Greek “proteios” meaning ‘of primary importance’
o First described and named by Swedish chemist Jons Jakob Berzelius in 1838
o James B. Sumner showed that enzyme urease was a protein in 1926
o Naturally occurring, unbranched polymer
 Monomer unit: amino acids
 After water, most abundant molecules in the cells, 15% of cell’s overall mass
o Elemental composition
 Carbon
 Hydrogen
 Nitrogen
 Oxygen
 Sulfur
 Metals
 Iron
 Phosphorus
- Amino Acids
o Monomer unit of protein
o Composition
 Amino group (-NH2)
 Alpha carbon
 Carboxyl group (-COOH)
 R-Side chain
o Over 700 amino acids are known
 20 Standard Amino acids, based on common R-groups
 All differing from one another by their R-Groups
o Divided into 4 groups, based on properties of the R-Groups
 Non-polar
 R-Groups are non-polar
 Hydrophobic
 9 Amino acids out of 20 are non-polar
o Located in the interior of protein, Where there is no polarity

Non-Polar Amino Acid Side chain Nomenclature

Glycine -H Gly, G
Alanine - CH3 Ala, A
Valine - CH(-CH3)-CH3 Val,V
Leucine - CH2-CH(-CH3)-CH3 Leu, L
Isoleucine - CH(-CH3)-CH2-CH3 Ile, I
Proline Five C ring, NH – COOH Pro, P
Phenylalanine - CH2-Benzene Phe, F
Methionine - CH2-CH2-S-CH3 Met, M
Tryptophan - CH2-Double 5 C ring, NH Trp, W
  Polar
 R-Groups are Polar
 Three types
o Polar-neutral
 Neutral side chains
 6 amino acids out of 20

Polar Neutral Amino Acid Side chain Nomenclature

Serine - CH2-OH Ser, S
Cysteine - CH2-SH Cys, C
Threonine - CH(-OH)-CH3 Thr, T
Asparagine - CH2-C(=O)-NH2 Asn, N
Glutamine - CH2-CH2-C(=O)-NH2 Gln, Q
Tyrosine - CH2-Phenol Ring Tyr, Y

o Polar acidic
 Carboxyl group as part of the side chains
 2 amino acids out of 20

Polar Acidic Amino Acid Side chain Nomenclature

Aspartic Acid - CH2-COOH Asp, D
Glutamic Acid - CH2-CH2-COOH Glu, E

o Polar basic
 Amino group as part of the side chain
 3 amino acids out of 20

Polar Basic Amino Acid Side chain Nomenclature

Histidine - CH2-Five Ring NH-N His, H
Lysine - CH2-CH2-CH2-CH2-NH2 Lys, K
Arginine - CH2-CH2-CH2-NH-C(=NH)-NH2 Arg, R

Nomenclature

- Common names are assigned to the amino acids

o Three letter abbreviations
 First letter of amino acid is compulsory, capitalized, and followed by next two
letters
 Exceptions
o Asparagine (Asn)
o Glutamine (Gln)
o Tryptophan (Trp)
o One letter symbol
 Commonly used for comparing amino acid in sequences of proteins
  Usually, the first letter of the name
 When more than one amino acid has the same letter, most abundant amino
acid gets the 1st letter
o All alpha carbons in amino acids are Chiral, except Glycine.
 They also are enantiomers

Essential Amino Acids

- Not synthesized by the body, must be sourced from diet.

o Phenylalanine
o Valine
o Tryptophan
o Threonine
o Isoleucine
o Methionine
o Histidine
o Lysine
o Leucine

Chirality

- Amino acids and proteins in nature are L-isomers

o Bacteria have some D-amino acids
o Monosaccharides nature favors D-isomers

Acid-Base Properties of Amino Acids

- Amino acids are White crystalline solids in pure form

o Decomposes before they melt
o Not very soluble in water
- Under physiological conditions, exists as Zwitterions
o An ion with +Positive and -Negative charges on the same molecule net zero change
 Carboxyl groups give up a proton to get negative charge
 Amino groups accept a proton to become positive charge
- Amino acids in solution exists in three different species and Equilibrium shifts with change in pH
o Zwitterions
o Positive ion
o Negative Ion
- Isoelectric point (pI)
o pH at which Zwitterion conc. Is at max-net charge is zero
o Amino acids are not attracted towards applied electric field

Cysteine

- The only standard amino acid with Sulfhydryl group (-SH group).
o Imparting a unique chemical property
- Forms Cystine in presence of mild oxidizing agents (Dimerizes)
 o Two cysteine residues linked via a covalent disulfide bond

Peptides

- Bonding of proteins, covalently-bonded amino acids are called Peptide Bonds

- Covalently-linked chains of amino acids are called Peptides
o Has N-terminal end (NH3+) and a C-terminal end (COO-)
- Under proper conditions, amino acids can bond together to produce an unbranched chain of
amino acids
- Dipeptide
o Between two amino acids
- Oligopeptide
o ~10-20 amino acids
- Polypeptide
o Between large number of amino acids
- Nomenclature
o C-terminal amino acid residue keeps its full amino acid name
o All amino acids residues have names ending in -yl.
 -ine or -ic acid ending is replaced with -yl, except Trp where -yl is added
 Naming sequence begins at N-terminal
o N-terminal – C-terminal
 Ala-leu-gly
 Alanylleucylglycine

Isomeric Peptides

- Peptides that contain same amino acids but differ in order are entirely different with different
properties
o Number of isomeric peptides increases rapidly as the length of the peptide chain
increases.

Important small peptides

- Many relatively small peptides are biochemically active

o Hormones
 ADH/Vasopressin
 Oxytocin
 Both produced by the pituitary glands
 Nonapeptide with six residues held in a loop by a disulfide bond
between 2 cysteine residues
o Neurotransmitters
 Enkephalins are pentapeptide neurotransmitters,
 Help reduce pain
 Met-enkephalin
o Tyr-Gly-Gly-Phe-Met
 Leu-enkephalin
 o Tyr-Gly-Gly-Phe-Leu
o Antioxidants
 Glutathione
 Glu-Cys-Gly
 Tripeptide present in high levels in most cell
 Regulator of oxidation-reduction reactions
 Protects cellular contents from oxidizing agents such as peroxides and
superoxides
o Highly reactive forms of oxygen often generated within the cell
in response to bacterial invasion
 Unusual structural feature – Glu is bonded to Cys through the side-chain
carboxyl group.

General Structural Characteristics of Proteins

- General definition
o Protein naturally occurring, unbranched polymer in which the monomer units are amino
acids.
- Specific definition
o Protein is a peptide in which at least 40 amino acid residues are present
 Terms polypeptide and protein are often used interchangeably used to describe
a protein
 Several proteins with > 10,000 amino acid residues are known
 Common proteins contain 400-500 amino acid residues
 Small proteins contain 40-100 amino acid residues
o More than one peptide chain may be present
 Monomeric
 One peptide chain
 Multimeric
 More than one peptide chain

Protein classification based on chemical composition

- Simple proteins
o A protein in which only amino acid residues are present
o More than one protein subunit may be present but all subunits contain only amino acids
- Conjugated protein
o Protein that has one or more non-amino acid entities (Prosthetic groups) present in its
structure
 One or more polypeptide chains may be present
 Non-amino acid components may be organic or inorganic prosthetic groups
 Lipoproteins
 Lipid prosthetic groups
 Glycoproteins
 Carbohydrate groups
  Metalloproteins
 Specific metal as prosthetic group

Protein Structure

- Four types
o Primary
 Order in which amino acids are linked together in a protein
 Each protein has its own unique amino acid sequence
 Frederick Sanger (1953) sequenced and determined the primary
structure of the first protein – Insulin. Differences in 8, 9, 10, and 30
o Human: Thr-Ser-Ile, Thr
o Porcine: Thr-Ser-Ile, Ala
o Bovine: Ala-Ser-Val, Ala
o Secondary
 Arrangement of atoms of backbone in space
 2 common types
 Alpha-helix
o Single protein chain that is coiled
o H-bonding, R-group outside of the helix
 Beta-pleated sheet
o Extended amino acid chains
o H-bonding, R-chains below/above axis
 Peptide linkages are planar
 Cis-trans isomerism is possible about C-N bond
 Trans isomer is preferred
o Tertiary
 3D shape of a protein
 4 types of interaction
 Disulfide bond between 2 cysteine group
 Electrostatic interactions
o Salt bridge between acidic A.A. and basic A.A.
 H-bonding, attached on O, N, or F
 Hydrophobic between non-polar
o Quaternary
 Organization among various peptide chains in multimeric protein
 Highest level of protein organization
 Only with 2 or more polypeptide chains
 Subunits are independent of each other
 Oligomeric proteins
 Even number of subunits

Protein Classification based on shape

- Fibrous
 o Characteristics
 Elongated shape
 Insoluble in water
 Secondary, simple, regular, linear structure; Hair, nails, etc.
o Alpha-Keratin
 Protective coating for organs
 Hair, feather, nails, horns, turtle shells
 Hydrophobic a.a. residues
 Hardness dependent on S-S bonds
 More S-S bonds, more harder
o Collagen
 Most abundant protein in humans (30%)
 Tendons, ligaments, blood vessels, and skin
 Organic component of bone and teeth
 Triple-helix
 Rich in proline (20%)
- Globular
o Characteristics
 Spherical or globular shape
 Water soluble
 Hydrophobic a.a. residues in protein core
 Enzymes, intracellular signaling molecules
o Myoglobin
 Oxygen storage in muscles
 Reserve oxygen source
 Monomer: single peptide chain, 1 heme unit
 Binds 1 O2 molecule
 Higher Oxygen affinity than hemoglobin
o Hemoglobin
 Oxygen carrier in blood
 Up to 4 oxygen molecules at a time
 From lungs to tissues
 Tetramer; each with heme group
 Iron in heme interacts with oxygen
- Membrane
o Characteristics
 Cell membranes
 Insoluble in water
 Hydrophobic a.a. residues on the surface
 Transport molecules across membrane

Protein classification based on function

- Catalytic proteins
o Enzymes catalyzes almost every chem reaction in body
 - Defense proteins
o Immunoglobulins or antibodies
- Transport proteins
- Messenger proteins
o Insulin, Glucagon – carb metabolism
o HGH – body growth
- Contractile proteins
o For movements
 Actin, Myosin – muscles
 As well as in sperms
- Structural proteins
o For stiffness and rigidity
o Collagen, in cartilages
o Keratin, in hair, nails, etc.
- Transmembrane proteins
o Control movement of small molecules and ions
 Have channels
 Selective transport
- Storage proteins
o Bind and store small molecules
 Ferritin
 Iron storage protein
 Myoglobin
 Oxygen storage protein
- Regulatory proteins
o In exterior surfaces of cell membranes
 Site for receptor molecules
 Binds to enzymes, controlling enzymatic action

Protein hydrolysis

- Reverse of peptide bond formation

o Generation of an amine and carboxylic acid
o Digestion is enzyme-catalyzed hydrolysis

Protein Denaturation

- Disorganization of protein’s tertiary structure

o Cooking
 Denatures the protein, but does not change its nutritional value
 Kills microorganisms by denaturing their proteins
 Fever
o Coagulation
 Precipitation

Glycoproteins
 - Conjugated proteins, with carbs linked
o Plasma membranes
o Blood group markers, ABO system
o Collagen and immunoglobulins
- Immunoglobulins
o Protective response to invasion

Lipoprotein

- Conjugated protein, containing lipids and a.a.

- Help suspend lipids transporting them through the blood stream
- 4 major classes
o Chylomicrons
 Transport dietary TAG from intestine to liver and adipose tissues
o VLDL
 Transport TAG in liver to adipose tissues
o LDL
 Transport cholesterol in liver to cells
o HDL
 Collect excess cholesterol from tissues and transport it back to liver to turn to
bile acids
 Good cholesterol

Diseases involving proteins

- Protein misfolding disorders

o From mutant proteins
 Folds abnormally and aggregates
 Impairs cellular functions
o Associated with neurodegenerative diseases
- Protein deficiency diseases
o Kwarshorkor
 Edematous malnutrition
 Associated with edema
 Lack of protein in diet
 In areas with famine
o Marasmus
 Severe malnutrition
 Energy deficiency
 Usually occurring on children
- Amino acid metabolism disorders
o Deficiency of enzyme or transporter
 Phenyl ketonuria
 A.A. Phe, F
 Enz. Phe hydroxylase
  Seizures, intellectual disability
 Alkaptonuria/Black urine disease
 A.A. Tyr, Y
 Enz. Homogentisate-1,2-dioxygenase
 Urine turns black exposed to air
 Branched chain ketoaciduria/Maple syrup urine disease
 A.A., Leu, L. Ile. I. Val, V.
 Enz. Alpha-keto acid dehydrogenase
 Sweet urine odor, lethargy, seizure
 Homocystinuria
 A.A. Met, M
 Enz. Cystathione-beta-synthase
 Nearsightedness, abnormal blood clots, retinal detachment