CORRELATE: AMINO ACIDS AND PROTEINS (DR. CORAZON TAN-MENESES)
Structure and Characteristics
COVERAGE • Optical Activity
• Amino Acids − A tetrahedral carbon atom → four distinct constituents → chiral
− Common Amino Acids vs. Derived Amino Acids − Chirality describes the handedness of a molecule that is observable by
− Metabolic Roles/Functions the ability of a molecule to rotate the plane of polarized light either to
− Structure and Characteristics the right (dextrorotatory) or to the left (levorotatory)
− Classifications
− Acid-Base Property and Others
− Functional Significance of R groups • Steroisomerism
− Chemical Reactions − D and L isomerism (enantiomers)
− Amino Acids Analysis − All amino acids in proteins’ absolute steric configuration as L-
• Peptides glyceraldehyde
− Examples ▪ All are L--amino acids
• Proteins − D-amino acids are never found in proteins, although they exist in
− Classifications nature
− Metabolic Roles/Functions − D-amino acids are often found in polypeptide antibiotics
− Protein Structures
− Protein Folding Classification
− Prion Diseases • Each of the 20 -amino acids can be distinguished by the R-group substitution
− Denaturation of Protein − Two broad classes: whether the R-group is hydrophobic or
− Separation/Purification of Proteins hydrophilic
▪ Hydrophobic amino acids
AMINO ACIDS ▪ Hydrophilic amino acids
→ Polar uncharged amino acids
Common Amino Acids → Charged amino acids (+/-)
• Coded for by a specific codon on genetic code • Nonpolar, aliphatic R groups
• There are 20 amino acids that make up mammalian proteins − Alanine, Valine, Leucine, Methionine, Isoleucine
• Selenocysteine, 21st amino acid – 25 • Polar, uncharged R groups
− Serine, Threonine, Cysteine, Asparagine, Glutamine
Derived Amino Acids • Aromatic R groups
• Post-translational modification of amino acids in protein − Phenylalanine, Tyrosine, Tryptophan (indole ring)
• Examples • Positively charged R groups
− 4-Hydroxyproline (collagen) − Lysine, Arginine, Histidine (imidazole group)
− 5-Hydroxylysine (collagen) • Negatively charged R groups
− Phosphoserine (glycogen phosphorylase) − Aspartate (Aspartic acid), Glutamate (Glutamic acid)
− -carboxyglutamate (Vitami K dependent clotting factors – II, VII, IX, • Glycine and Proline (pyrrolidine ring, imino acid) can either be polar or
X) nonpolar
Metabolic Roles/Functions Selenocysteine
• Amino acids → active amine (histamine), neurotransmitters (catecholamines, • 21st amino acid
GABA) • Selenium instead of S inserted into protein during translation (unusual tRNA)
• Amino acids in proteins → serve distinct functions e.g. tyrosine in thyroid • Peroxidases and reductases → Thioredoxin reductase (nucleotide metabolism),
hormones Glutathione (GSH) peroxidase (protects membrane lipids and hemoglobin
• Glycine and glutamate → neurotransmitters against oxidation by peroxides), Deiodinase (converts Thyroxine, T4, into T3)
• All peptides and polypeptides are polymers of L--amino acids • Impairment in selenoproteins → tumorigenesis, atherosclerosis, Keshan
• Several other amino acids are found in the body free disease (selenium deficiency cardiomyopathy)
• Combined states (i.e. not associated with peptides or proteins) → perform
specialized functions (creatine, heme)
, Acid-Base Property and Others Functional Significance of R-Groups
• The -COOH and -NH2 groups are capable of ionizing, as are the acidic and • The hydrophilic amino acids
basic R-groups of the amino acids − Generally found on the exterior of proteins
• The equilibrium reactions − In the active centers of enzymatically active proteins
− R-COOH R-COO- + H+ • The imidazole ring of Histidine (pK = 6) allows it to act as either a proton donor
− R-NH3+ R-NH2 + H+ • At least two weakly acidic groups or acceptor at physiological pH
• The acidic-strength of the carboxyl, amino, and ionizable R-groups in amino − Found in the reactive center of enzymes
acids is defined by the association constant, Ka or more commonly the negative − The ability of Histidine in hemoglobin to buffer the H+ ions from
logarithm of Ka, pKa carbonic acid ionization in red blood cells allows it to exchange O2 and
• The carboxyl group is a far stronger acid than the amino group CO2 at the tissues or lungs, respectively
− At pH 7.4: • The primary alcohol of Serine and thiol (-SH) of Cysteine → act as nucleophiles
▪ Carboxyl group → unprotonated (pK = 2 – 3) during enzymatic catalysis
▪ Amino group → protonated (pK = 9 – 10) − Thiol of Cysteine → form a disulfide bond with other cysteine
• The acid is protonated and when proton is released → forms its conjugate base • The hydroxyl amino acids (Serine, Threonine) form hydrogen bonds with their
• The base form associates with a proton to form the respective acid hydroxyl group. They also form covalent bonds with carbohydrates in
• The dissociation of an acid is referre to as its dissociation constant (K) and its glycoproteins and with phosphate in phosphoproteins
pK • The hydroxyl group of Tyrosine carries a covalently bound phosphate group in
• The actual pK depends on the environment in which acid group is placed some phosphoproteins
(polarity & charged group) • The aromatic R-groups in amino acids absorb ultraviolet light with an
• An amino acid with no ionizable R-group would be electrically neutral at this absorbance maximum in the range of 280 nm
pH. This species is termed a zwitterion (“twin ions”) − The ability of proteins to absorb ultraviolet light is predominantly due
• When the net charge of an amino acid or protein is zero, the pH will be to the presence of the tryptophan which strongly absorbs UV light
equivalent to the isoelectric point (pI)
− pI = 1
pK +pK2 Amino Acids in Protein Structure
2 • The hydrophobic amino acids are generally found in the interior of proteins
shielded from direct contact with water
• The net charge of any amino acid, peptide, or protein will depend upon the pH
• The hydrophilic amino acids are generally found on the exterior of proteins
of the surrounding aqueous environment
• The small amino acids, Glycine and Alanine, occupy little space → often found
• As the pH of a solution of an amino acid or protein changes, so too does the net
in places where two polypeptide chains have to come close together
charge
• Proline → with its nitrogen tied into a ring structure → being stiff and angled→
• Charged groups on amino acids → soluble in polar solvents
often found at bends in the polypeptide
• High melting points → high energy required to disrupt ionic forces that
stabilize the crystal lattice Chemical Reactions
• In solution, the nature of the amino acid R-groups and its ability to form • Peptide bond formation
noncovalent interactions and the covalent bonds dictate the structure-function
− Linkages between amino acyl residues in peptides and proteins
relationships of peptides and proteins
− Formed by the condensation of the carboxyl group of one amino acid
• Nothing in thecell works without proteins
with the amino group of the second with the concomitant elimination
• Membrane proteins join hands with the fibrous proteins of the cytoplasm and of water
the extracellular matrix to keep cells and tissues in shape
− The peptide bond is a resonance hybrid of two structures
• Enzyme proteins catalyze metabloic reactions; and
− Partial double-bond character inhibits rotation (rigid) around the
• DNA- binding proteins regulate gene expression peptide bond
− Four atoms bound to the carbonyl carbon and amide nitrogen form a
Proteomics and Proteome
plane → coplanar
• Human body → thousands of cell types → thousands of proteins
− Trans configuration
• Proteomics → identify the entire complement of proteins elaborated by a cell
• Schiff base formation = Transamination
under diverse conditions
• Decarboxylation of amino acids → amines
• Proteome → set of all the proteins expressed by an individual cell at a
• Reaction with Ninhydrin (oxidative decarboxylation)
particular time
− Ruheman’s purple (570 nm)
− Proline = yellow compound (440 nm)
Structure and Characteristics
COVERAGE • Optical Activity
• Amino Acids − A tetrahedral carbon atom → four distinct constituents → chiral
− Common Amino Acids vs. Derived Amino Acids − Chirality describes the handedness of a molecule that is observable by
− Metabolic Roles/Functions the ability of a molecule to rotate the plane of polarized light either to
− Structure and Characteristics the right (dextrorotatory) or to the left (levorotatory)
− Classifications
− Acid-Base Property and Others
− Functional Significance of R groups • Steroisomerism
− Chemical Reactions − D and L isomerism (enantiomers)
− Amino Acids Analysis − All amino acids in proteins’ absolute steric configuration as L-
• Peptides glyceraldehyde
− Examples ▪ All are L--amino acids
• Proteins − D-amino acids are never found in proteins, although they exist in
− Classifications nature
− Metabolic Roles/Functions − D-amino acids are often found in polypeptide antibiotics
− Protein Structures
− Protein Folding Classification
− Prion Diseases • Each of the 20 -amino acids can be distinguished by the R-group substitution
− Denaturation of Protein − Two broad classes: whether the R-group is hydrophobic or
− Separation/Purification of Proteins hydrophilic
▪ Hydrophobic amino acids
AMINO ACIDS ▪ Hydrophilic amino acids
→ Polar uncharged amino acids
Common Amino Acids → Charged amino acids (+/-)
• Coded for by a specific codon on genetic code • Nonpolar, aliphatic R groups
• There are 20 amino acids that make up mammalian proteins − Alanine, Valine, Leucine, Methionine, Isoleucine
• Selenocysteine, 21st amino acid – 25 • Polar, uncharged R groups
− Serine, Threonine, Cysteine, Asparagine, Glutamine
Derived Amino Acids • Aromatic R groups
• Post-translational modification of amino acids in protein − Phenylalanine, Tyrosine, Tryptophan (indole ring)
• Examples • Positively charged R groups
− 4-Hydroxyproline (collagen) − Lysine, Arginine, Histidine (imidazole group)
− 5-Hydroxylysine (collagen) • Negatively charged R groups
− Phosphoserine (glycogen phosphorylase) − Aspartate (Aspartic acid), Glutamate (Glutamic acid)
− -carboxyglutamate (Vitami K dependent clotting factors – II, VII, IX, • Glycine and Proline (pyrrolidine ring, imino acid) can either be polar or
X) nonpolar
Metabolic Roles/Functions Selenocysteine
• Amino acids → active amine (histamine), neurotransmitters (catecholamines, • 21st amino acid
GABA) • Selenium instead of S inserted into protein during translation (unusual tRNA)
• Amino acids in proteins → serve distinct functions e.g. tyrosine in thyroid • Peroxidases and reductases → Thioredoxin reductase (nucleotide metabolism),
hormones Glutathione (GSH) peroxidase (protects membrane lipids and hemoglobin
• Glycine and glutamate → neurotransmitters against oxidation by peroxides), Deiodinase (converts Thyroxine, T4, into T3)
• All peptides and polypeptides are polymers of L--amino acids • Impairment in selenoproteins → tumorigenesis, atherosclerosis, Keshan
• Several other amino acids are found in the body free disease (selenium deficiency cardiomyopathy)
• Combined states (i.e. not associated with peptides or proteins) → perform
specialized functions (creatine, heme)
, Acid-Base Property and Others Functional Significance of R-Groups
• The -COOH and -NH2 groups are capable of ionizing, as are the acidic and • The hydrophilic amino acids
basic R-groups of the amino acids − Generally found on the exterior of proteins
• The equilibrium reactions − In the active centers of enzymatically active proteins
− R-COOH R-COO- + H+ • The imidazole ring of Histidine (pK = 6) allows it to act as either a proton donor
− R-NH3+ R-NH2 + H+ • At least two weakly acidic groups or acceptor at physiological pH
• The acidic-strength of the carboxyl, amino, and ionizable R-groups in amino − Found in the reactive center of enzymes
acids is defined by the association constant, Ka or more commonly the negative − The ability of Histidine in hemoglobin to buffer the H+ ions from
logarithm of Ka, pKa carbonic acid ionization in red blood cells allows it to exchange O2 and
• The carboxyl group is a far stronger acid than the amino group CO2 at the tissues or lungs, respectively
− At pH 7.4: • The primary alcohol of Serine and thiol (-SH) of Cysteine → act as nucleophiles
▪ Carboxyl group → unprotonated (pK = 2 – 3) during enzymatic catalysis
▪ Amino group → protonated (pK = 9 – 10) − Thiol of Cysteine → form a disulfide bond with other cysteine
• The acid is protonated and when proton is released → forms its conjugate base • The hydroxyl amino acids (Serine, Threonine) form hydrogen bonds with their
• The base form associates with a proton to form the respective acid hydroxyl group. They also form covalent bonds with carbohydrates in
• The dissociation of an acid is referre to as its dissociation constant (K) and its glycoproteins and with phosphate in phosphoproteins
pK • The hydroxyl group of Tyrosine carries a covalently bound phosphate group in
• The actual pK depends on the environment in which acid group is placed some phosphoproteins
(polarity & charged group) • The aromatic R-groups in amino acids absorb ultraviolet light with an
• An amino acid with no ionizable R-group would be electrically neutral at this absorbance maximum in the range of 280 nm
pH. This species is termed a zwitterion (“twin ions”) − The ability of proteins to absorb ultraviolet light is predominantly due
• When the net charge of an amino acid or protein is zero, the pH will be to the presence of the tryptophan which strongly absorbs UV light
equivalent to the isoelectric point (pI)
− pI = 1
pK +pK2 Amino Acids in Protein Structure
2 • The hydrophobic amino acids are generally found in the interior of proteins
shielded from direct contact with water
• The net charge of any amino acid, peptide, or protein will depend upon the pH
• The hydrophilic amino acids are generally found on the exterior of proteins
of the surrounding aqueous environment
• The small amino acids, Glycine and Alanine, occupy little space → often found
• As the pH of a solution of an amino acid or protein changes, so too does the net
in places where two polypeptide chains have to come close together
charge
• Proline → with its nitrogen tied into a ring structure → being stiff and angled→
• Charged groups on amino acids → soluble in polar solvents
often found at bends in the polypeptide
• High melting points → high energy required to disrupt ionic forces that
stabilize the crystal lattice Chemical Reactions
• In solution, the nature of the amino acid R-groups and its ability to form • Peptide bond formation
noncovalent interactions and the covalent bonds dictate the structure-function
− Linkages between amino acyl residues in peptides and proteins
relationships of peptides and proteins
− Formed by the condensation of the carboxyl group of one amino acid
• Nothing in thecell works without proteins
with the amino group of the second with the concomitant elimination
• Membrane proteins join hands with the fibrous proteins of the cytoplasm and of water
the extracellular matrix to keep cells and tissues in shape
− The peptide bond is a resonance hybrid of two structures
• Enzyme proteins catalyze metabloic reactions; and
− Partial double-bond character inhibits rotation (rigid) around the
• DNA- binding proteins regulate gene expression peptide bond
− Four atoms bound to the carbonyl carbon and amide nitrogen form a
Proteomics and Proteome
plane → coplanar
• Human body → thousands of cell types → thousands of proteins
− Trans configuration
• Proteomics → identify the entire complement of proteins elaborated by a cell
• Schiff base formation = Transamination
under diverse conditions
• Decarboxylation of amino acids → amines
• Proteome → set of all the proteins expressed by an individual cell at a
• Reaction with Ninhydrin (oxidative decarboxylation)
particular time
− Ruheman’s purple (570 nm)
− Proline = yellow compound (440 nm)
