LICEO DE CAGAYAN UNIVERSITY

COLLEGE OF MEDICINE
BIOCHEMISTRY 1ST BIMONTHLY
AUGUST 11, 2020

Fernandez, Ann Ross L. 20200733258

AMINO ACIDS AND PEPTIDE

LEARNING OBJECTIVES:

1. Define Amino acid

An amino acid is a molecule that contains at least one carboxyl (COOH) group and one amino
(NH2) group.
2. Explain the biomedical importance of amino acids and peptides
Both D-amino acids and non- α amino acids occur in anture, but proteins are synthesized using
only L- α amino acids. L-α-Amino acids provide the monomer units of the long polypeptide chains
of proteins. L-α Amino acids serve vital metabolic functions in addition to protein synthesis.
Examples include the biosynthesis of urea, heme, nucleic acids, and hormones such as
epinephrine and DOPA. Certain microorganisms secrete free D-amino acids. Several of these
bacterial peptides are of therapeutic value while some microbial peptides are toxic.
3. Diagram the structure and write the –three-and one-letter designation for each of the amino acids
present in proteins.

Name Symbol Structural Formula

Glycine Gly [G]

Alanine Ala [A]

Valine Val [V]

Leucine Leu [L]

Isoleucine Ile [I]

Serine Ser [S]

Threonine Thr [T]

 Tyrosine Tyr [Y]

Cystine Cys [C]

Methionine Met [M]

Aspartic Acid Asp [D]

Asparagine Asn [N]

Glutamic Acid Glu [E]

Glutamine Gln [Q]

Arginine Arg [R]

Lysine Lys [K]

Histidine His [H]

Phenylalanine Phe [F]

Tryptophan Trp [W]

Proline Pro [P]

4. Discuss the different classification of amino acids

Amino acid side chains can be classified either by polarity (charged, nonpolar hydrophobic, or
uncharged polar) or structural features (aliphatic, cyclic, or aromatic).
Amino acids with aliphatic (open-chain hydrocarbon) nonpolar side chains and exhibit a high
degree of hydrophobicity. Electrons are shared equally between the carbon and hydrogen atoms
in these side chains, so that they cannot hydrogen bond with water, and therefore, the side chains
do not interact with water. Within proteins, these amino acid side chains will cluster together to
form hydrophobic cores. Their association is also promoted by van der Waals forces between the
positively charged nucleus of one atom and the electron cloud of another. This force is effective
over short distances when many atoms pack closely together
Aromatic amino acids contain ring structures with similar properties. However, the polarity of these
amino acids differ because some rings have substituents, while others do not (e.g.
Phenylalanine). In the case of phenylalanine, its 6-member carbon-hydrogen ring is already
sharing their electrons equally, leaving nothing for hydrogen bonding and resulting in a nonpolar
hydrophobic structure.
 Aliphatic, polar, uncharged amino acids are those with side chains containing hydroxylic (OH)
groups, or an amide group. For the amino acids Aspartic acid [Asp] and Glutamic acid [Glu],they
are the amides of Asparagine [Asn] and Glutamine [Gln] respectively. Asn and Gln are under the
classification acidic amino acids, and they carry a negative charge.
Acidic and basic amino acids have a carboxylic acid group that carry a negative charge (acidic) or
have side chains that contain nitrogen that can be protonated and positively charged at
physiological and lower pH values (basic).
Sulfur containing amino acids contains a sulfur group (such as Methionine) or a sulfuhydryl group
(such as Cysteine). The difference between the two is that Cysteine is able to form disulfide (S—
S) bonds between two Cysteine sulfuhydryl groups, while Methionine cannot form disulfide bonds.
Cysteine’s tendency to form disulfide bonds with other Cysteine sulfuhydryl groups does not make
it very soluble in water. Relatedly, Methionine is nonpolar and has a very bulky side chain that is
hydrophobic.
The amino acid proline is the only cyclic amino acid.
5. Describe and identify the different amino acids with alipathic side chains, side chains containing
hydroxylic groups, side chain containing sulfur atoms, side chain containing acidic groups or their
amides and side chain containing basic groups.
Amino acids with aliphatic side chains include Glycine, Alanine, Valine, Leucine, and Isoleucine.
As mentioned, these amino acids have an open-chain hydrocarbon and exhibit a high degree of
hydrophobicity.
Amino acids whose side chains contain hydroxylic (OH) groups are Serine, Threonine, and
Tyrosine. These amino acids are polar.
Amino acids with side chains containing sulfur atoms are Cysteine and Methionine. The difference
between the two is that Cysteine is able to form disulfide (S—S) bonds between two Cysteine
sulfuhydryl groups, while Methionine cannot form disulfide bonds. Cysteine’s tendency to form
disulfide bonds with other Cysteine sulfuhydryl groups does not make it very soluble in water.
Relatedly, Methionine is nonpolar and has a very bulky side chain that is hydrophobic.
Amino acids whose side chain contains acidic groups are Aspartic acid (aka Aspartate) and
Glutamic acid (aka Glutamate). These two acidic amino acids carry a negative charge and are
polar. The amides of these two are Asparagine and Glutamine, respectively. Asparagine and
Glutamine are polar but uncharged.
Amino acids containing basic groups are Arginine, Lysine, and Histidine. As mentioned, the side
chain of these amino acids contain nitrogen that can be protonated and positively charged at
physiological and lower pH values, thus, they are classified as basic amino acids.
6. Describe and identify the different amino acids containing aromatic rings and imino acid.
Amino acids which contain aromatic rings are Histidine, Phenylalanine, Tyrosine, and Tryptophan.
These amino acids contain an aromatic 6-member carbon-hydrogen ring with three conjugated
(i.e. separated by a single bond) double bonds. These hydrogen atoms do not participate in
hydrogen bonding. Although these amino acids contain an aromatic ring, they differ in their
polarity. Their polarity depends on whether their carbon-hydrogen rings have substituents or not.
The amino acid proline contains a ring involving its α-carbon and its α-amino group, which are part
of the peptide backbone. It is an imino acid. This rigid ring causes a kink in the peptide backbone
that prevents it from forming its usual configuration, and it will restrict the conformation of the
protein at that point.
7. Discuss the classification of amino acids according to the following:
a. Structure of side chains – As mentioned, amino acids can be classified according to
structural features such as aliphatic, cyclic, or aromatic. Those with aliphatic side chains
have an open-chain hydrocarbon. Those with aromatic side chains have a 6-member
carbon ring with three conjugated double bonds. The only cyclic amino acid is proline which
is characterized by a ring which involves its alpha-carbon and alpha-amino group, resulting
in a very rigid ring that causes a kink in the peptide backbone.
b. Polarity of side chain – Amino acids can be classified by polarity such as charged, nonpolar
hydrophobic, or uncharged polar. Those with charged side chains contain acidic groups or
basic groups – and these are polar.
Nonpolar hydrophobic side chains are neither polar nor charged (i.e. nonpolar aliphatic)
Electrons are shared equally between the carbon and hydrogen atoms in these side chains,
 so that they cannot hydrogen bond with water, and therefore, the side chains do not
interact with water.
Polar uncharged side chains either contain amides (such as Asparagine and Glutamine) or
hydroxylic groups (such as Serine and Threonine). These groups in the side chains allow
these amino acids to form hydrogen bonds with water, with each other and the peptide
backbone, or with other polar compounds in the binding sites of the proteins.
c. Nutritional requirements
Amino acids can be classified in terms of nutritional requirements in humans. The
biosynthesis of proteins requires the presence of all the constituent amino acids. If one of
the 20 amino acids is missing or in short suppply, protein biosynthesis is inhibited
(Campbell & Farrell, 2012, p. 666). Humans cannot synthesize 10 of the L-alpha amino
acids present in proteins in amounts adequate to support infant growth and maintain adult
health. Consequently, the human diet must contain adequate quantities of these
nutritionally essential amino acids. Some of the essential (or needed) amino acids can be
synthesized by the body, but not in sufficient quantities for its needs, especially in the case
of growing children.
The 10 essential amino acids include arginine, histidine, isoleucine, leucine, methionine,
phenylalanine, threonine, tryptophan, and valine. The 10 nonessential amino acids are
alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, and
tyrosine.
d. Metabolic fate
Amino acids can be classified as either glucogenic, ketogenic, or both when we consider
how their carbon skeletons are broken down (Campbell & Farrell, p. 666). A glucogenic
amino acid yields pyruvate or oxaloacetate on degradation. Oxaloacetate is the starting
poitn for th eproductions of glucose by gluconeogenesis. A ketogenic amino acid breaks
down to acetyl-COA or acetoacetyl-COA, leading to the formation of ketone bodies.
Ketogenic amino acids consist of leucine and lysine. Amino acids which are both
glucogenic and ketogenic (i.e. having more than one pathway for catabolism) include
isoleucine, phenylalanine, tryptophan, and tyrosine. The twelve other amino acids are
glucogenic (e.g. aspartic acid, alanine, glycine).
8. Explain the contribution of each type of R group of the protein amino acids to their chemical
properties.
Each functional group of an amino acid exhibits all of its characteristic chemical reactions.
For carboxylic acid groups, these reactions include the formation of esters, amides, and acid
anhydrides; for amino groups, acylation, amidation, and esterification; and for —OH and —SH
groups,oxidation and esterification. Since glycine, the smallest amino acid, can be accommodated
in places inaccessible to other amino acids, it often occurs where peptides bend sharply.
The hydrophobic R groups of alanine, valine, leucine, and isoleucine and the aromatic R groups of
phenylalanine, tyrosine, and tryptophan typically occur primarily in the interior of cytosolic proteins.
The charged R groups of basic and acidic amino acids stabilize specific protein conformations via
ionic interactions, or salt bridges. These interactions also function in “charge relay” systems during
enzymatic catalysis and electron transport in respiring mitochondria.
Histidine plays unique roles in enzymatic catalysis. The pKa of its imidazole proton permits
histidine to function at neutral pH as either a base or an acid catalyst without the need for any
environmentally induced shift.
The primary alcohol group of serine and the primary thioalcohol (—SH) group of cysteine are
excellent nucleophiles, and can function as such during enzymatic catalysis. For selenocysteine,
its pK3 of 5.2 is 3 pH units lower than that of cysteine, 8.3. At a distinctly acidic pH, selenocysteine
thus should be the better nucleophile. However, the secondary alcohol group of threonine, while a
good nucleophile, is not known to serve this role in catalysis. The —OH groups of serine, tyrosine,
and threonine frequently serve as the points of covalent attachment for phosphoryl groups that
regulate protein function.
9. List additional key functions of amino acids and explain how certain amino acids in plant seeds
can severely impact human health.
L-α-Amino acids fulfill vital metabolic roles in addition to serving as the“building blocks” of proteins.
For example, tyrosine is a precursor of thyroid hormone, and both tyrosine and phenylalanine are
 metabolized to epinephrine, norepinephrine, and dihydroxyphenylalanine (DOPA).Glutamate is
both a neurotransmitter and the precursor of Gamma-aminobutyric acid (GABA). Ornithine and
citrulline are intermediates in urea biosynthesis, and homocysteine, homoserine, and glutamate-γ-
semialdehyde are intermediates in the metabolism of the protein amino acids.
The consumption of plants that contain certain nonprotein amino acids can adversely impact
human health. The seeds and seed products of three species of the legume Lathyrus have been
implicated in the genesis of neurolathyrism, a profound neurologic disorder characterized by
progressive and irreversible spastic paralysis of the legs.
The seeds of certain Lathyrus species also contain α,γ-diaminobutyric acid, which as an analog of
ornithine inhibits the hepatic urea cycle enzyme ornithine transcarbamylase, disrupts the urea
cycle, and leads to ammonia toxicity. Finally, L-β-methylaminoalanine, a neurotoxic amino acid
that is presentin Cycad seeds, has been implicated as a risk factor for neurodegenerative
diseases.
10. Name the ionizable groups of the protein amino acids and list their approximate pKa values as
free amino acids in aqueous solution.
In a free amino acid, the carboxyl group (-COOH) and amino group (NH 3+ ) of the amino acid are
charged or ionized at physiologic pH (pH 7.4).

Dissociating group pKa Range

α-Carboxyl 3.5 – 4.0
Non- α COOH of Asp or Glu 4.0 – 4.8
Imidazole of His 6.5 – 7.4
SH of Cys 8.5 – 9.0
OH of Tyr 9.5 – 10.5
α-Amino 8.0 – 9.0
e-Amino of Lys 9.8 – 10.4
Guanidium of Arg ~12.0

11. Define pI and explain its relationship to the net charge on a polyfunctional electrolyte.
The isoelectric pH, also called the pI, is the pH midway between pKa values for the ionizations on
either side of the isoelectric species. At its isoelectric pH (pI), an amino acid bears no net charge.
12. Explain how pH, pKa and pI can be used to predict the mobility of a polyelectrolyte, such as an
amino acid, in a direct-current electrical field.
The pKa values of all functional groups of an amino acid or of a peptide dictate its net charge at a
given pH. The isoelectric pH (pI) is the pH at which an amino acid bears no net charge and thus
does not move in a direct current electrical field.
13. Describe the directionality, nomenclature, and primary structure of peptides.
Amino acids build proteins by connecting the carboxyl group of one amino acid with the amino
group of the next amino acid. Amino acids are linked together by peptide bonds. The number and
order of the amino acid residues in a polypeptide constitute its primary structure. Amino acids
present in peptides, called aminoacyl residues, are referred to by replacing the ate or ine suffixes
of free amino acids with yl (eg, alanyl, aspartyl, tyrosyl). Peptides are then named as derivatives of
the carboxy terminal aminoacyl residue.
For example, Lys-Leu-Tyr-Gln is called lysyl-leucyl-tyrosyl-glutamine. The ine ending on the
carboxy-terminal residue (eg, glutamine) indicates that its α-carboxyl group is not involved in a
peptide bond. Three-letter abbreviations linked by straight lines represent an unambiguous
primary structure. Lines are omitted when using single-letter abbreviations.
Prefixes like tri- or octa- denote peptides with three or eight residues,respectively. By convention,
peptides are written with the residue thatbears the free α-amino group at the left. This convention
was adopted long before it was discovered that peptides are synthesized in vivo starting fromthe
amino-terminal residue.
14. Describe the conformational consequences of the partial double-bond character of the peptide
bond and identify the bonds in the peptide backbone that are free to rotate.
The bond that connects a carbonyl carbon to the α-nitrogen exhibits a partial double-bond
character. As such, this bond cannot rotate. Consequently, the O, C, N, and H atoms of a peptide
bond are coplanar.The imposed semirigidity of the peptide bond has important consequences for
the manner in which peptides and proteins fold to generate higher orders of structure.
 Free rotation can occur about the bonds that connect the α-carbon with the α-nitrogen and with
the α- carbonyl carbon. The extended polypeptide chain is thus a semirigid structure with two-
thirds of the atoms of the backbone held in a fixed planar relationship to one another.

REFERENCE:
Harper’s Illustrated Biochemistry 31ST edition
Campbell, M.K., & Farrell, S.O. (2012). Biochemistry (7th edition). Boston, MA: Cengage Learning.