proteins-1 Flashcards
protein intro
In 1839 Dutch chemist GJ Mulder while investigating
substances such as those found in milk, egg found that
they could be coagulated on heating and were nitroge-
nous compounds. Swedish scientist JJ Berzelius
suggested to Mulder that these substances should be
called proteins. The term is derived from Greek word
Proteios means “primary”, or “holding first place” or
“pre-eminent” because Berzelius thought them to be most
important of biological substances. And now we know
that proteins are fundamental structural components of
the body. They are nitrogenous “macromolecules”
composed of many amino acids.
biomedical importance of proteins
- Proteins are the main structural components of the
cytoskeleton. They are the sole source to replace Nitrogen
of the body. - Biochemical catalysts known as enzymes are proteins.
- Proteins known as immunoglobulins serve as the first line
of defence against bacterial and viral infections. - Several hormones are protein in nature.
- Structural proteins furnish mechanical support and some
of them like actin and myosin are contractile proteins and
help in the movement of muscle fibre, microvilli, etc. - Some proteins present in cell membrane, cytoplasm and
nucleus of the cell act as receptors. - The transport proteins carry out the function of trans-
porting specific substances either across the membrane
or in the body fluids.
* Storage proteins bind with specific substances and store
them, e.g. iron is stored as ferritin.
* Few proteins are constituents of respiratory pigments and
occur in electron transport chain or respiratory chain, e.g.
cytochromes, hemoglobin, myoglobin.
* Under certain conditions proteins can be catabolised to
supply energy.
* Proteins by means of exerting osmotic pressure help in
maintenance of electrolyte and water balance in body.
composition of proteins
In addition to C, H, and O which are present in carbo-
hydrates and lipids, proteins also contain N. The nitrogen
content is around 16 per cent of the molecular weight of
proteins. Small amounts of S and P are also present. Few
proteins contain other elements such as I, Cu, Mn, Zn
and Fe, etc.
amino acids
acids: Protein molecules are very large molecules
with a high molecular weight ranging from 5000 to
25,00,000. Protein can be broken down into smaller units
by hydrolysis. These small units the monomers of
proteins are called as amino acids. Proteins are made up
from, 20 such standard amino acids in different sequences
and numbers. So an indefinite number of proteins can be
formed and do occur in nature. Thus proteins are the
unbranched polymers of L- α-amino acids.
R is called a side chain and can be a hydrogen,
aliphatic, aromatic or heterocyclic group. Each amino
acid has an amino group –NH2, a carboxylic acid group
– COOH and a hydrogen atom each attached to carbon
located next to the – COOH group. Thus the side chain
varies from one amino acid to the other.
classification of amino acids
Amino acids can be classified into 3 groups depending
on their reaction in solution.
A. Neutral
B. Acidic and
C. Basic.
neutral amino acids
A. Neutral amino acids: This is the largest group of
amino acids and can be further subdivided into aliphatic,
aromatic, heterocyclic and S-containing amino acids.
aliphatic amino acids (neutral)-simple monoamino monocarboxy-
lic acids.
- Glycine (Gly) or α-amino acetic acid.
- Alanine (Ala) or α-amino propionic acid.
- Valine (Val) or α-amino-isovaleric acid.
- Leucine (Leu) or α-amino-isocaproic acid.
- Isoleucine (Ile) or α-amino-β-methyl valeric acid.
hydroxy group amino acids
- Serine (Ser) or α-amino-β-hydroxy propionic acid.
- Threonine (Thr) or α-amino-β-hydroxybutyric acid.
aromatic amino aciids
Second subgroup of neutral amino acids consists of
aromatic amino acids.
8. Phenylalanine (Phe) or α-amino-β-phenyl propionic
acid.
- Tyrosine (Tyr) or parahydroxy phenylalanine or
α-amino-β-parahydroxy phenylpropionic acid.
(c) Heterocyclic Amino Acids: Third group belongs to
heterocyclic amino acids.
10. Tryptophan (Trp) or α-amino-β-3-indole propionic
acid. This amino acid is often considered as aromatic
amino acid since it has aromatic ring in its structure.
- Histidine (His) or α-amino-β-imidazole propionic
Histidine is basic in solution on account of the
imidazole ring and often considered as Basic Amino acid.
(d) Imino Acids - Proline (Pro) or Pyrrolidone-2-carboxylic acid.
- Hydroxyproline (Hyp) or 4 hydroxy pyrrolidone-2
carboxylic acid.
Proline and Hydroxyproline do not have a free –NH2
group but only a basic pyrrolidone ring in which the
Nitrogen of the Imino group is in a ring but can still
function in the formation of peptides. These amino acids
are therefore called as imino acids.
(e) ‘S’ containing amino acids: The fourth subgroup of
neutral amino acids contains two sulphur containing
amino acids.
14. Cysteine (Cys) or α-amino-β-mercaptopropionic
acid.
Two molecules of cysteine make cystine (cys-cys) or
dithio β, β-α aminopropionic acid. The S–S linkage is
called as disulphide bridge.
- Methionine (Met) or α-amino γ-methylthio-η-butyric
acidic amino acids
These amino acids have two
–COOH groups and one – NH2 group. They are therefore
monoaminodicarboxylic acids.
- Aspartic acid (Asp) or α-amino succinic acid.
Asparagine (Asn) or γ -amide of α-aminosuccinic acid.
- Glutamic Acid (Glu) or α-aminoglutaric acid.
Glutamine (Gln)-Amide of Glutamic Acid or δ-amide of
α-aminoglutaric acid.
basic amino acids
C. Basic amino acids: This class of amino acids consists
of those amino acids which have one – COOH group and
two –NH2 groups. Thus they are diamino monocarboxy-
lic acids. Arginine, lysine and hydroxylysine are included
in this group.
18. Arginine (Arg) or α-amino- δ-guanidino-n-valeric acid.
- Lysine (Lys) or α- ε-diamino caproic acid.
- Hydroxylysine (Hyl) or α-ε-diamino-δ-hydroxy-n-
valeric acid.
As already mentioned histidine is also classified as
basic amino acid.
non-standard similar to amino acids but not in proteins
A. The compounds similar to basic structure of amino
acids but do not occur in proteins. Examples of some of
those are:
* β-alanine: They found in coenzyme A.
* Taurine: They found in bile acids
* Ornithine and citrulline: They are intermediates in
urea cycle
* Thyroxine (T4) and Tri-iodo Thyronine (T3): Thyroid
hormones synthesised from tyrosine.
* γ-aminobutyric acid (GABA): A neurotransmitter
produced from glutamic acid.
* β-amino isobutyric acid: These are end product of
pyrimidine metabolism.
- δ-aminolaevulinic acid (δ-ALA): These are inter-
mediate in haem synthesis. - S-adenosyl methionine (SAM): These are methyl
donor formed from L-methionine - 3, 4-dihydroxy phenyl alanine (DOPA): A precursor
of mela nine pigment.
non standard D amino acids
B. D-amino acids: These are non-standard amino acids—
Amino acids normally isolated from animal and plants are
L-amino acids. But certain D-amino acids are found in
bacteria and antibiotics and in brain tissues of animals.
* D-glutamic acid and D-Alanine are constituents of
bacterial cell walls.
* D-amino acids are found in certain antibiotics, e.g.
gramicidin-S, Actinomycin-D.
* Animal tissues contain L-amino acids which are
deaminated by L-amino acid oxidase. But there is also
present D-amino acid oxidase the function of which
was not known. Now D-amino acids like D-aspartate
and D-serine have been found in brain tissue. This
explains the existence of D-amino acid oxidase.
functions of amino acids
Apart from being the monomeric constituents of proteins and
peptides, amino acids serve variety of functions.
(a) Some amino acids are converted to carbohydrates and
are called as glucogenic amino acids.
(b) Specific amino acids give rise to specialised products, e.g.
* Tyrosine forms hormones such as thyroid hormones,
(T3, T4), epinephrine and norepinephrine and a
pigment called melanin.
* Tryptophan can synthesise a vitamin called niacin.
* Glycine, arginine and methionine synthesise creatine.
* Glycine and cysteine help in synthesis of Bile salts.
* Glutamate, cysteine and glycine synthesise glutathione.
* Histidine changes to histamine on decarboxylation.
* Serotonin is formed from tryptophan.
* Glycine is used for the synthesis of haem.
* Pyrimidines and purines use several amino acids for
their synthesis such as aspartate and glutamine for
pyrimidines and glycine, aspartic acid, Glutamine and
serine for purine synthesis.
(c) Some amino acids such as glycine and cysteine are used
as detoxicants of specific substances.
(d) Methionine acts as “active” methionine (S-adenosyl-
methionine) and transfers methyl group to various
substances by transmethylation.
(e) Cystine and methionine are sources of sulphur.
essential amino acids types
Nutritionally, amino acids are of two types: (a) Essential
and (b) Non-essential. (c) There is also a third group of
semi-essential amino acids.
essential amino acids
These are the ones which are
not synthesised by the body and must be taken in diet.
They include valine, leucine, isoleucine, phenylalanine,
threonine, tryptophan, methionine and lysine. For
remembering the following formula is used—MATT VIL
PHLY.
non-essential amino acids
They can be synthesised
by the body and may not be the requisite components of
the diet.
semi-essential amino acids
(c) Semi-essential amino acids: These are growth
promoting factors since they are not synthesised in
sufficient quantity during growth. They include arginine
and histidine. They become essential in growing children,
pregnancy and lactating women.
occurance of amino acids
All the standard amino acids
mentioned above occur in almost all proteins. Cereals are
rich in acidic amino acids Asp and Glu while collagen is
rich in basic amino acids and also proline and hydroxy-
proline.
new amino acids
In addition to 20 L-amino acids that take part in protein
synthesis, recently two more new amino acids described.
They are:
A. Selenocysteine - 21st amino acids
B. Pyrrolysine - 22nd amino acid
selenocysteine
Selenocysteine is recently introduced as 21st amino acid.
Selenocysteine occurs at the “active site” of several
enzymes.
Examples include:
* Thioredoxin reductase
* Glutathione peroxidase which scavenges peroxides,
- De-iodinase that converts thyroxine to tri-
iodothyronine - Glycine reductase
- Selenoprotein P, a glycoprotein containing 10
selenocysteine residues, found in mammalian blood.
It has an antioxidant function and its concentration
falls in selenium deficiency.
Selenocysteine arises co-translationally during its
incorporation into peptides. The UGA anticodon of the
unusual tRNA designated tRNAsec, normally signals
STOP.
The ability of the protein synthesising apparatus to
identify a selenocysteine specific UGA codon involves
the selenocysteine insertion element, a stem-loop
structure in the untranslated region of the m-RNA.
Selenocysteine-tRNAsec is first charged with serine by
the Ligase that charges tRNAsec. Subsequent replacement
of the serine oxygen by selenium involves seleno-
phosphate formed by Selenophosphate synthetase.
pyrrolysine
Recently it has been claimed as 22nd amino acid by some
scientists. The STOP codon UAG can code for
pyrrolysine.
properties of amino acids
-isomerism
-amphoteric nature and isoelectric pH
-chemical properties
isomerism
Two types of isomerism are shown by
amino acids basically due to the presence of asymmetric
carbon atom. Glycine has no asymmetric carbon atom
in its structure hence is optically inactive.
(a) Stereoisomerism: All amino acids except glycine exist
in D and L isomers. As described in the chapter on carbo-
hydrates it is an absolute configuration. In D-amino acids
– NH2 group is on the right hand while in L-amino acids
it is oriented to the left. It is the same orientation of – OH
group of the central carbon of glyceraldehyde
Natural proteins of animals and plants generally
contain L-amino acids. D-amino acids occur in bacteria.
optical isomerism
All amino acids except glycine
have asymmetric carbon atom. Few amino acids like
isoleucine and threonine have an additional asymmetric
carbon in their structures. Consequently all but glycine
exhibit ‘optical’ activities and rotate the plane of plane
polarised light and exist as dextrorotatory (d) or
laevorotatory (l) isomers. Optical activity depends on
the pH and side chain.
amphoteric nature and isoelectric pH
The -NH2 and
-COOH groups of amino acids are ionizable groups.
Further, charged polar side chains of few amino acids
also ionise. Depending on the pH of the solution these
groups act as proton donors (acids) or proton acceptors
(bases). This property is called as amphoteric and
therefore amino acids are called as ampholytes. At a
specific pH the ami11no acid carries both the charges in
equal number and exists as dipolar ion or “Zwitterion”.
At this point the net charge on it is zero, i.e. positive
charges and negative charges on the protein/amino acid
molecule equalizes. The pH at which it occurs without
any charge on it is called pI or isoelectric pH. On the
acidic side of its pI amino acids exist as a cation by
accepting a proton and on alkaline as anion by donating
a proton.
physical properties
They are colourless, crystalline
substances, more soluble in water than in polar solvents.
Tyrosine is soluble in hot water. They have high melting
point usually more than 200°C. They have a high dielectric
constant. They possess a large dipole moment.
chemical properties
due to carboxylic group
1- formation of esters
2-reduction to amino alcohol
3-formation of amines by decarboxylation
4-formation of amides
properties due to amino group
-formation of acyl derivatives
-salt formation with acids
-oxidation
-reaction with HNO2
-reaction with CO2
-reaction with formaldehyde
-specific color reaction
properties due to both
formation of esters
- Formation of esters: They can form esters with alcohols.
The COOH group can be esterified with alcohol.
Treatment with Na2CO3 solution in cold releases the free
ester from ester hydrochloride.
reduction to amino alcohol
- Reduction to amino alcohol: This is achieved in pre-
sence of lithium aluminium hydride.
formation of amines by decarboxylation
- Formation of amines by decarboxylation: Action of
specific amino acid decarboxylases, dry distillation or
heating with Ba(OH)2 or with diphenylamine evolves
CO2 from the —COOH group and changes the amino
acid into its amine (Fig. 6.2).
In vivo, the amino acids can be decarboxylated by
the enzyme decarboxylase and forms the corresponding
amines.
formation of amide
- Formation of amides: Anhydrous NH3 may replace
alcohol from its combination with an amino acid in an
amino acid ester so that an amide of amino acid and a
molecule of free alcohol is produced
