CHEM 153 : AMINO ACIDS & PROTEINS
growth hormones
Proteins
• Naturally-occurring, unbranched
polymer of amino acids
• Provide nitrogen and sulfur for the diet
• Carry out most of the work of the cell
• Composed of at least 40 amino acid
residues :
Amino Acids : Building blocks of Proteins
• Structure : Collagen and keraRn in skin,
bone, hair and nails
• Catalyst : ReacRons in living systems are
catalyzed by proteins (enzymes)
• Movement : Myosin and acRn in the
muscle
• Transport : Hemoglobin for oxygen
transport, and other transport proteins
(lipoproteins)
Cirelle Helaena U. Aristan
BSN 1 – NB
• Hormones : Insulin, oxytocin, and human
• ProtecRon : Fibrinogen for blood
cloXng, and anRbodies to fight diseases
• Storage : Casein in milk and ovalbumin in
eggs for storage of nutrients, and ferriRn
in liver for iron storage
• RegulaRon : Control of gene expression • Although 𝛼-amino acid are commonly
• Typically, 9000 different proteins is in a wri^en in the un-ionized form, they are
cell (10,000 in humans) more properly wri^en in the zwi^erion
• Can either be Fibrous or Globular (internal salt form)
o Zwi^erion : a posiRve charge on one
atom and a negaRve charge on
another atom
• Carbohydrates : monosaccharides
• Lipids : monosaccharides
Chirality of Amino Acids
• Compounds that contain an amino group
and carboxyl group • Excluding glycine (Gly, G), all protein-
derived amino acids have at least one
• 𝛼-amino acid
stereocenter (the 𝛼-carbon) and are
o Amino acids in which the amino
chiral
group and the carboxyl group are
a^ached to the 𝛼-carbon • Most of the protein-derived amino 𝛼-
amino acids have L-configuraRon at the
𝛼-carbon
 • Example : comparison of
stereochemistry of D-Glyceraldehyde
and L-Alanine

• Polar Neutral Amino Acids : contains

polar, uncharged side chains

Protein-Derived Amino Acids

• Non-polar Amino Acids : contains non-
polar (hydrophobic) side chains • All 20 are 𝛼-amino acid
• Polar Acidic/Basic Amino Acids : contains • For 19 of the 20 amino acids, the 𝛼-
polar, charged side chains amino group is primary; for proline (Pro,
P), it is secondary
• Except glycine, the 𝛼-carbon of each is a
stereocenter
• Isoleucine (Ile, I) and Threonine (Thr, T)
each contains a second stereocenter

Cirelle Helaena U. Aristan

BSN 1 – NB
IonizaRon vs pH
• The net charge on amino acid depends
on the pH of the soluRon
• If an amino acid is dissolved in water (pH
= 7.0), it exists as zwi^erion
• Adding strong acid (HCl), pH becomes
2.0 or lower
o Acid donates H+ to the COO- of the
amino acid, turning the zwi^erion to
a posiRvely charged ion
o pH < 7.0
• Adding a strong base (NaOH), pH
becomes 10.0 or higher
o NH3+ of the amino acid is transferred
to the base, turning the zwi^erion
to a negaRvely charged ion
o pH > 7.0
Cirelle Helaena U. Aristan
BSN 1 – NB
Isoelectric Point
• pH where majority of molecules have no
net charge
• Tyrosine and Phenylalanine : precursor
to norepinephrine and epinephrine (i.e.
catecholamines)
Cysteine
• chemically unique amino acid
• amino acid with -SH (suliydryl) group
Uncommon Amino Acids
• Post-translaRonal modificaRon
o ModificaRon of amino acids by
certain organisms aker biosynthesis
Amino Acids with AromaRc Side Chains • HydroxylaRon (oxidaRon) of proline,
• Key precursor to neurotransmi^ers lysine, and tyrosine
• Tryptophan : Converted to serotonin (5-
hydroxytryptamine)
 • IodinaRon of tyrosine
o Animals and humans exhibit
sluggishness and slow metabolism
are oken given thyroxine to help
ramp up their metabolism
PepRdes
• Emil Fischer proposed that proteins are
long chains of amino acids joined by
amide bonds (1902)
• PepRde bond
o Amide bond between the 𝛼-
carboxyl group of one amino acid
and the 𝛼-amino group of another
amino acid
Cirelle Helaena U. Aristan
BSN 1 – NB
• PepRde
o A short polymer of amino acids
joined by pepRde bonds; classified
by the number of amino acid
• PolypepRde
residues
o A macromolecule composed of
• DipepRde amino acids connected by a pepRde
o A molecule composed of two (2) bond
amino acids connected by a pepRde
• Protein
bond
o A biological macromolecule
containing at least 30 to 50 amino
acids connected by a pepRde bond
• TripepRde
o A molecule composed of three (3)
amino acids connected by a pepRde
bond WriRng PepRdes
• ConvenRon : Lek to right, starRng with
free -NH3+ group and ending with -COO-
group
 • C-terminal amino acid : amino acid at
the end of the chain bearing the -COO-
group
• N-terminal amino acid : amino acid at
the beginning of the chain bearing the
-NH3+ group
PepRdes and Proteins
• Proteins behave as zwi^erion and have
an isoelectric point (pI)
• At pH > pI (more basic)
o Net negaRve charge
• At pH < pI (more acidic)
o Net posiRve charge
• Hemoglobin has almost equal number of
acidic and basic side chains; its pI is 6.8
• Serum albumin has more acidic side
chains; its pI is 4.9
• Proteins are least soluble in water at
their isoelectric point and can be
precipitated from soluRon at this pH
Cirelle Helaena U. Aristan
BSN 1 – NB
Levels of Protein Structure than the number of atoms in the
universe
o Human insulin consist of two
polypepRde chains having a total of
51 amino acids; the two chains are
connected by two interchain
disulfide bonds
• Primary Structure
o Sequence of amino acids in a
polypepRde chain
o TranslaRon of informaRon contained
in genes
o The number of pepRdes possible
from the 20 protein-derived amino
o Vasopressin and oxytocin are both
acids is enormous
nonapepRdes but different
o Rule of Thumb : 20n = number of
biological funcRons
pepRdes possible with n number of
o Vasopressin is an anRdiureRc
amino acids
hormone
o For small proteins of 60 amino acids,
the number of proteins possible is
2060 = 1078, which is possible greater
 o Oxytocin affects contracRon of the
uterus in childbirth and the muscle
of the breast that aid in the
secreRon of milk
o In 𝛼-helix :
• Secondary Structure
o ConformaRon of amino acids in
localized regions of a polypepRde
chain
o Commonly 𝛼-helix and β–pleated
sheet
o 𝛼-helix : a secRon of polypepRde
chain coils into spiral, most
commonly a right-handed spiral
o β–pleated sheet : two polypepRde
chains or secRons of the same
polypepRde chain align parallel to
each other (parallel or anRparallel)
Cirelle Helaena U. Aristan
BSN 1 – NB
o In β–pleated sheet:
§ 3.6 amino acids per turn of the
helix
§ Six atoms of each pepRde bond
lie on the same plane
§ N-H groups of amide bonds
point in the same direcRon,
roughly parallel to the axis of
the helix
§ C=O group of amide bonds
point in the opposite direcRon,
roughly parallel to the axis of
the helix
§ Hydrogen bonding between
C=O and N-H groups exist
§ All R-side chains points outward
the helix
§ Six atoms of each pepRde bond
lie on the same plane
§ The C=O and N-H groups of
pepRde bonds from adjacent
chains point toward each other
and are in the same plane so
that the hydrogen bonding is
possible between them
§ All R- side chains on any one
chain alternate. First above,
then below the plane of the
sheets, etc.

Collagen Triple Helix
• Tropocollagen : Three polypepRde
chains wrapped around each other
forming a triple helix
• Collagen : A structural protein of
connecRve Rssues (bone, carRlage,
tendon, blood vessels, skin)
• 30 amino acids in each are proline (Pro,
P) and L-hydroxyproline (Hyp);
L-hydroxylysine (Hyl) also occurs
• Every third posiRon is glycine and
repeaRng sequence are X-Pro-Gly and
X-Hyp-Gly
• Each polypepRde chain is a helix but not
𝛼-helix
• The three strands are held by hydrogen
bonding between hydroxyproline and
hydroxylysine
• During aging, collagen helices becomes
cross-linked by covalent bonds between
the side chains of lysine
Cirelle Helaena U. Aristan
BSN 1 – NB
§ Salt Bridges : a^racRon of the
-NH3+ group of lysine and the
COO- group of asparRc acid
§ Hydrophobic interacRon :
interacRon between non-polar
side chains (e.g. side chains of
phenylalanine and isoleucine)
§ Metal interacRon : interacRon
of same charged side chains
with a metal ion in between
• TerRary Structure
o Overall conformaRon of an enRre
polypepRde chain
o TerRary structure are stabilized
through the following :
§ Covalent bonds : disulfide
bonds between cysteine side
chains
§ Hydrogen bonding : interacRon
between polar groups of the
side chains (e.g. -OH group of
serine and threonine)
 § Hydrophobic interacRon : o The 8 β strands in these eight
interacRon between non-polar structural moRfs associate in the
side chains (e.g. side chains of center of the molecule to form β-
phenylalanine and isoleucine) barrel
o In Hemoglobin :
§ Adult Hemoglobin : two alpha
chains of 141 amino acids each
and two beta chains of 146
amino acids each
§ Each chain surrounds an iron-
containing heme unit
§ Fetal Hemoglobin : two alpha
chains, and two gamma chains;
has greater affinity to oxygen
relaRve to adult hemoglobin

• Quaternary Structure
o Arrangement of polypepRde chains
into a non-covalently bonded
aggregaRon
o Quaternary structure are stabilized
through :
§ Hydrogen bonding : interacRon
between polar groups of side
chains (-OH group of serine and
threonine)
§ Salt Bridges : a^racRon of the
-NH3+ group of lysine and the
COO- group of asparRc acid
Hemoglobin
o 1 RSS = Ribosomal Protein S7 from
Thermus thermophilus
o 2AWK = Green Fluorescent Protein
(GFP) R96M mature chromophore
• Oxygen binds to heme in hemoglobin
o When one O2 bind, the binding of
the next O2 is easier
• The first 2,3-bisphospho-glycerate to
leave deoxyhemoglobin
• During binding, shape changes which
favors more reacRon of oxygen

Cirelle Helaena U. Aristan

BSN 1 – NB

DenaturaRon
• H from metabolizing cells (low pH)
+ • DestrucRon of naRve conformaRon of
favors oxygen release from Hb
o When oxygen concentraRon is low,
as in the peripheral Rssues, H is
bound and O2 is released
• Higher pH in the lungs favors binding of
oxygen to Hb
o When oxygen concentraRon is high,
as in the lungs, hemoglobin binds O2
and releases protons
Oxygen Transport : Mother-Fetus
• Fetal Hb is different from adult Hb
o It does not bind to BPG and has
higher affinity to O2
Cirelle Helaena U. Aristan
BSN 1 – NB
• Sickle cell hemoglobin (Hb S) has a valine
subsRtuted for glutamic acid in the beta
chain
• Deoxy version clumping and forming the
characterisRc sickle cells
• Early death; sickle cell trait = malaria
resistance
protein by physical or chemical means
• Some denaturaRon are reversible, while
some are permanent
• DenaturaRon includes :
o Heat : disrupts hydrogen bonding; in
globular proteins, it can lead to
unfolding of polypepRde chains
which might result in coagulaRon
and precipitaRon
o 6M aqueous area : disrupts
hydrogen bonding
o Surface-acRve agents : disrupts
hydrogen bonding (detergent)
o Reducing agents : cleavage of
disulfide bonds through reducRon
(2-mercaptoethanol)
o Heavy metal ions : formaRon of
water-insoluble salts with thiol side
chains (Pb2+, Hg2+, and Cd2+)
o Alcohol : sterilizaRon of skin before
injecRon due to complete
denaturaRon of proteins (70%
ethanol)
Protein DigesRon and Diet
• DigesRon : DegradaRon of proteins in
the diet
o Stomach : Facilitated by enzyme,
pepsin
o Small intesRne : trypsin,
chymotrypsin, elastase, etc.
• EssenRal Amino Acids : cannot be
synthesized by humans
o Ile, Leu, Lys, Met, Phe, Thr, Try, Val,
His
• Complete protein from animal provides
essenRal AA in proper proporRons
• Imbalanced protein from vegetable
sources must be balanced (e.g., beans
(Lys + Trp) and corn (Met))