AMINO ACIDS AND

PROTEINS
BS I BIOCHEMISTRY
By Ms Nimra Maqsood
Biomedical Importance of Amino Acids

 In addition to providing the monomer units from which the long polypeptide chains of proteins are
synthesized, the l-αamino acids and their derivatives participate in cellular functions as diverse as
nerve transmission and the biosynthesis of porphyrins, purines, pyrimidines, and urea.
 The neuroendocrine system employs short polymers of amino acids called peptides as hormones,
hormone-releasing factors, neuromodulators, and neurotransmitters.
 Humans and other higher animals cannot synthesize 10 of the l-α-amino acids present in proteins in
amounts adequate to support infant growth or to maintain adult health.
 Consequently, the human diet must contain adequate quantities of these nutritionally essential
amino acids.
 Each day the kidneys filter over 50 g of free amino acids from the arterial renal blood.
 However, only traces of free amino acids normally appear in the urine because amino acids
are almost totally reabsorbed in the proximal tubule, conserving them for protein synthesis
and other vital functions.
 Not all amino acids are, however, beneficial. While their proteins contain only l-α-amino
acids, some microorganisms secrete mixtures of d-amino acids.
 Many bacteria elaborate peptides that contain both d- and l-α-amino acids, several of
which possess therapeutic value, including the antibiotics bacitracin and gramicidin A and
the antitumor agent bleomycin.
 Certain other microbial peptides are toxic.
 The cyanobacterial peptides microcystin and nodularin are lethal in large doses, while small
quantities promote the formation of hepatic tumors.
 The ingestion of certain amino acids present in the seeds of legumes of the genus Lathyrus
results in lathyrism, a tragic irreversible disease in which individuals lose control of their
limbs.
PROPERTIES OF AMINO ACIDS

 Although more than 300 amino acids occur in nature, proteins are synthesized almost
exclusively from the set of 20 l-αamino acids encoded by nucleotide triplets called codons .
 Some proteins contain additional amino acids that arise by the post-translational modification
of an amino acid already present in a peptide.
 With the sole exception of glycine, the α-carbon of every amino acid is chiral. Although some
protein amino acids are dextrorotatory and some levorotatory, all share the absolute
configuration of l glyceraldehyde and thus are defined as l-α-amino acids.
 Essential amino acids are not synthesize by our body whereas non essential amino acids are
synthesized by our body.
 The R groups of amino acids determine their unique biochemical functions. Amino acids are
classified as basic, acidic, aromatic, aliphatic, or sulfur-containing based on the composition
and properties of their R groups.
D-Amino Acids
d-Amino acids that occur naturally include free d-serine and d-
aspartate in brain tissue, d-alanine and d-glutamate in the cell walls of
gram-positive bacteria, and d-amino acids in certain peptides and
antibiotics produced by bacteria, fungi, reptiles, and other
nonmammalian species. Bacillus subtilis excretes d-methionine, d-
tyrosine, d-leucine, and d-tryptophan to trigger biofilm disassembly,
and Vibrio cholerae incorporates d-leucine and d-methionine into the
peptide component of their peptidoglycan layer.
Peptide Bond
 A peptide bond is a chemical bond formed between two
molecules when the carboxyl group of one molecule reacts
with the amino group of the other molecule, releasing a
molecule of water (H2O).
 Peptides are named for the number of amino acid residues
present, and as derivatives of the carboxyl terminal residue.
 The primary structure of a peptide is its amino acid
sequence, starting from the amino-terminal residue, a
direction in which peptides actually are synthesized in vivo.
 The peptide bond has partial double-bond character.
PROTEINS
 Proteins may be classified based on their solubility, shape, or function or on the presence of a
prosthetic group, such as heme.
 The gene-encoded primary structure of a polypeptide is the sequence of its amino acids. Its
secondary structure results from folding of polypeptides into hydrogen-bonded motifs such as the
α helix, the β pleated sheet, β bends, and loops. Combinations of these motifs can form
supersecondary motifs.
 Tertiary structure concerns the relationships between secondary structural domains. Quaternary
structure of proteins with two or more polypeptides (oligomeric proteins) concerns the spatial
relationships between various types of polypeptides.
 Primary structures are stabilized by covalent peptide bonds. Higher orders of structure are
stabilized by weak forces— multiple hydrogen bonds, salt (electrostatic) bonds, and association of
hydrophobic R groups.
PROTEIN CLASSIFICATION
 Globular proteins
These proteins are water soluble and spherical includes enzymes, transporters, actin and hormones.
 Fibrous proteins
A Fibrous protein is a protein with an elongated shape. Fibrous proteins provide structural support for cells and
tissues. There are special types of helices present in two fibrous proteins α-keratin and collagen. These proteins
form long fibers that serve a structural role in the human body.
 Lipoproteins
Lipoproteins are special particles made up of droplets of fats surrounded by a single layer of phospholipid
molecules. Phospholipids are molecules of fats which are attached to a phosphorus-containing group. They are
distinctive in being amphipathic, which means they have both polar and non-polar ends.
 Integral membrane proteins
An integral membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological
membrane. All transmembrane proteins are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a
significant fraction of the proteins encoded in an organism's genome.
 Metalloproteins
Metalloprotein is a generic term for a protein that contains a metal ion cofactor. A large proportion of all proteins
are part of this category. For instance, at least 1000 human proteins (out of ~20,000) contain zinc-binding protein
domains although there may be up to 3000 human zinc metalloproteins.
The alpha helix (α-helix)
It is a common motif in the secondary structure of
proteins and is a right hand-helix conformation in which
every backbone N−H group hydrogen bonds to the
backbone C=O group of the amino acid located three or
four residues earlier along the protein sequence.
The β-sheet
 β-pleated sheet) is a common motif of regular
secondary structure in proteins.
 Beta sheets consist of beta strands (also β-strand)
connected laterally by at least two or three backbone
hydrogen bonds, forming a generally twisted, pleated
sheet.
 A β-strand is a stretch of polypeptide chain typically 3
to 10 amino acids long with backbone in an extended
conformation.
 The supramolecular association of β-sheets has been
implicated in formation of the protein aggregates and
fibrils observed in many human diseases, notably the
amyloidoses such as Alzheimer's disease.
Protein tertiary structure
 The three dimensional shape of a
protein.
 The tertiary structure will have a single
polypeptide chain "backbone" with one
or more protein secondary structures,
the protein domains.
 Amino acid side chains may interact
and bond in a number of ways. The
interactions and bonds of side chains
within a particular protein determine
its tertiary structure.
Quaternary Structure

 The quaternary structure of a protein is the

association of several protein chains or
Subunits into a closely packed arrangement.
Each of the subunits has its own primary,
secondary, and tertiary structure.
 The subunits are held together by hydrogen
bonds and van der Waals forces between
nonpolar side chains.
 Hemoglobin consists of two pairs of
different proteins, each protein is bound to
a molecule of heme.
 The heme is known as a prosthetic group.
An Fe(II) ion at the center of the heme is the
site of oxygen binding.
PERTURBATION OF PROTEIN CONFORMATION MAY HAVE PATHOLOGIC CONSEQUENCES

Prions
The transmissible spongiform encephalopathies, or prion diseases, are fatal neurodegenerative diseases characterized
by spongiform changes, astrocytic gliomas, and neuronal loss resulting from the deposition of insoluble protein
aggregates in neural cells. They include Creutzfeldt-Jakob disease in humans, scrapie in sheep, and bovine spongiform
encephalopathy (mad cow disease) in cattle. prion diseases are protein conformation diseases transmitted by altering
the conformation, and hence the physical properties, of proteins endogenous to the host.

Alzheimer’s Disease
Refolding or misfolding of another protein endogenous to human brain tissue, β-amyloid, is a prominent feature of the
Alzheimer’s disease. While the main cause of the Alzheimer’s disease remains elusive, the characteristic senile plaques
and neurofibrillary bundles contain aggregates of the protein β-amyloid, a 4.3-kDa polypeptide produced by proteolytic
cleavage of a larger protein known as amyloid precursor protein.

Beta-Thalassemias
Thalassemias are caused by genetic defects that impair the synthesis of one of the polypeptide subunits of hemoglobin