Amino Acids

Presented by

Dr. Mohammad Saadeh

The requirements for the Pharmaceutical Biochemistry I

Philadelphia University

Faculty of pharmacy

االحماض األمينية

Cell Structure

Amino Acids

The study of proteins has occupied biochemists to

understand three dimensional shapes, and chemical

activities of proteins may be key to the most scientific

challenge.

1. Thermophilic bacteria thrive at high temperatures.

What is the different about the proteins?

2. HIV-1 associated with AIDS.

The most important biological function of

proteins 1. Many proteins function as enzymes, the biochemical catalysts.

2. Proteins bind other molecules for storage and transport,

myoglobin and hemoglobin

3. Protein such as tubulin, actin, and collagen, provide support

and shape to cells.

4. Proteins can do mechanicals work, movement of flagella,

separation chromosome at mitosis, contraction of muscles.

5. Proteins play decoding information in the cell, translation,

regulating gene expression.

6. Proteins are hormones, which regulate biochemical activity in

target cells or tissues.

7. Proteins have highly specialized functions, Antibody, and

toxin.

I. General structure of Amino acids

• About 300 a.a have been found in nature but all

organisms use the same 20 a.a as building blocks for

the assembly of protein molecules. These 20 a.a are

called the common or standard a.a.

• Enormous variety of different polypeptides can be

produced by connecting the 20 standard a.a in various

combinations.

I. General structure of Amino acids

An a.a is a compound that

contains both a carboxyl

(-COOH) and amino (-NH2)

group as part of its structure.

In the 20 standard a.a that make

up proteins, the carboxyl and amino

groups are bonded to the same carbon atom,

called α -carbon. In addition, the amino acids in proteins

contain side chains that determine their role in the

proteins behavior.

I. General structure of Amino acids

Pka≈9 dipolar ions Pka≈3

Inside the cell, under normal physiological condition PH

6.8-7.4.

• The amino group are protonated (-NH3+), Pka≈9

• Carboxyl is ionize (-coo-), Pka≈3.

• So amino acid are zwitterions or dipolar ions, even

though their net charge may be zero.

I. General structure of Amino acids

• All 20 standard a.a except glycine is achiral, the α-carbon is chiral or asymmetric, since it has 4 different group bonded to it.

• Amino acid steroisomers are nonsuperimposable mirror image so it called enantiomers such as L and D isomers.

• Both L &D a.a are found in nature.

• Protein contain only L-a.a. but in bacteria D-a.a occur in bacterial cell walls and antibiotic of bacterial origin.

enantiomers

II. Structures of the common amino acids

• In fischer projection of a.a, horizontal bonds at a chiral center extend toward the viewer, and vertical bonds extend away.

• The properties of the side chains greatly influence the overall three- dimentional shape.

The RS system of configuration

II. Structures of the common amino acids 1. Aliphatic R groups

• Glycine is the smallest a.a, R group is

hydrogen atom, so it has little

hydrophobic character to the molecule.

• α-carbon is not chiral (achiral).

• Glycine play a unique in structure of

many proteins because the side chain is

small enough to fit into niches that can

accommodate no other a.a.

Glycine[G]

(Gly)

II. Structures of the common amino acids 1. Aliphatic R groups Alanine(Ala,A), Valine(Val,V), Leucine(Leu,L) and Isoleucine(Ile,I), have saturated side chains.

• Isoleucine, two carbon α&β are chiral so it have (22=4) stereoisomers (L&D. Isoleucine and L&D. alloisoleucine).

• Alanine, Valine, Leucine, Isoleucine are important in establishing and maintaining the three-dimensional structures because their cluster away from water.

• Valine, Leucine, Isoleucine are branched side chain, All three a.a are highly hydrophobic.

• Proline(Pro,P) differ from the other 19 a.a

• Three carbon side chain is bonded to the

nitrogen of its α-amino group, the α-carbon

creating a cyclic molecule.

• The heterocyclic pyrrolidine ring of

proline restrict the geometry of

polypeptide, sometimes introducing abrupt

changes in direction of the peptide chain.

• Cyclic structure of proline makes it much

less hydrophobic than valine, leucine,

isoleucine.

II. Structures of the common amino acids 1. Aliphatic R groups

• Phenylalanine (phe,F),Tyrosine

(Tyr,Y), Tryptophan (Trp, W)

have side chains with aromatic

groups.

• Phenylalanin has a hydrophobic

benzyle side chain,Tyrosine has

phenol group, Tryptophan

contain bicyclic indol group.

• Tyrosine(Tyr,Y), Tryptophan

are not hydrophobic as

Phenylalanine because the side

chains include polar groups

II. Structures of the common amino acids 2. Aromatic R groups

• All three aromatic a.a absorbe U.V because it contain delocalized π electron.

• At neutral PH, both tryptophan and tyrosine absorbe light at 280nm.

• Phenylalanine is almost transport at 280nm and absorbed light weakly at 260nm.

• Absorbance at 280 nm is used to estimate the concentration Of proteins in solutions.

II. Structures of the common amino acids 2. Aromatic R groups

Absorbance four times of tyrosine.

Absorption of light for tryptophan and tyrosine at pH6

• Methionine (Met, M), contain non polar thioether group, it one of more hydrophobic a.a. and play an important role in synthesis of protein, it is the first a.a in polypeptide chain.

• Cysteine(Cys, C), side chain somewhat hydrophobic and highly reactive. The sulfhydryl group of Cysteine form weak H-bonds with O, N. sulfhydryl group is weak acid, its lose proton to be come negative charge thiolate ion.

II. Structures of the common amino acids 3. Sulfur containing R groups

Cysteine

Methionine

II. Structures of the common amino acids 3. Sulfur containing R groups

• Cysteine don’t have to be close

together in amino acid sequence of

the polypeptide chain they found in

different chains.

• Disulfide bond, stabilize the three-

dimentional structures of some

peptide by covalently cross linking

cysteine residues in peptide chains.

• Inside the cell protein don’t contain

disulfide bond because the

condition not fever oxidation.

However, many secreted

extracellular protein contain

disulfide bridge. Oxidation at slightly alkaline pH, because

sulfhydryl groups are ionized at low pH.

The two Cysteine adjacent in three

dimention space to form disulfide bond

II. Structures of the common amino acids 4. Side chains with alcohol groups

• Serine and threonine have uncharged polar side

chains (β-hydroxyl groups). These give

hydrophilic character to aliphatic side chains.

• The hydroxyl groups of Serine and threonine

have the weak ionization properties of primary

and secondary alcohols.

• The hydroxymethyl group of serine dose not

appreciably ionized in aqueous solution;

nevertheless, this alcohol can react with active

site of No. of enzymes as thought it were ionized.

• Threonine has two chiral carbon so it have

(22=4) stereoisomers (L&D. threonine and

L&D. allothreonine ). (L-threonine in protein)

Threonine (Thr, T)

Serine (Ser, S)

II. Structures of the common amino acids 5. Basic R groups

• Histidine (His, H), Lysine (Lys, k), and arginine (Arg,R) have

hydrophilic side chains that are nitrogenous bases and are

positively charged

at pH 7.

• The side chain of histidine contains an imidazole ring substituent. The protonated from of this ring side chain is called an imidazolium ion.

Imidazole group Charged guanidino

group

Second primary amino

group at e position

II. Structures of the common amino acids 5. Basic R groups

Charged guanidino

group

Second primary amino

group at e position

• Lysine is diamino acid, having both α and ε as

an alkylammonium ion (-CH2NH3+) at neutral

pH and confers a positive charge in proteins.

• Arginine is the most basic acid of the 20 a.a its

side chain guanidinium ion is protonated under

all conditions normally found within a cell.

(Arginine side chains also contribute positive

charges in proteins).

II. Structures of the common amino acids 6. Acidic R groups and their amide derivatives

• Aspartate(Asp, D) and glutamate

(Glu, E) [aspartic acid or glutamic

acid] are dicarboxilic and have

negative charged hydrophilic side

chain at pH 7 (ionized).

• Monosodium glutamate (MSG),

which is used in food as flavoue

enhancer.

Carboxyl side chain

II. Structures of the common amino acids 6. Acidic R groups and their amide derivatives

• Asparagine(Asn, N) and glutamine

(Gln, Q) are amides of aspartic acid

or glutamic acid

• The side chains of Asparagine and

glutamine are uncharged, highly

polar and found on the surface on

proteins, where they can interact

with the water molecules.

• The polar amide groups of

Asparagine and glutamine can form

H-bonds with side chains of other

polar a.a.

amide side chains

II. Structures of the common amino acids 7. The hydrophobicity of amino acid side chains

• The relative hydrophobicity or

hydrophilicity of each a.a is called

hydropathy

• There are measuring hydropathy

according the tendency of an amino

acid to prefer a hydrophobic to

hydrophilic environment.

• In some scales tryptophan has a

much lower hydropathy value

II. Structures of the common amino acids 7. The hydrophobicity of amino acid side chains

• Hydropathy is important in protein

chain folding because hydrophobic

side chains to be clustered in the

interior of a protein and hydrophilic

residue are usually found on the

surface.

• Hydropathy used to predict which

segments of membrane-spanning

proteins are likely to be embedded

in hdrophobic lipid bilayer.

III. Other amino acids and amino acid derivatives

More than 200 different a.a are found in living

organisms.

• S-Adenosylmethionine, methyl doner. Many

species of bacteria & fungai synthesized D-amino

acids that are used in cell walls & antibiotic

(actionomycin).

• In the mammalian brain, glutamate is converted to

the neurotansmitter γ-aminobutyrate (GABA).

• Histamine is synthesized mammals from histidine,

to controls the constriction of certain blood vessels

and secretion of HCL by stomach.

III. Other amino acids and amino acid derivatives

• Tyrosine is metabolized to epinephrine

(adrenaline).

• Hormons that are regulate metabolism in

mammals. Tyrosine is the precursor of the

thyroid hormones thyroxin.

• Small amount of sodium iodide prevent

goiter (hypothyroidism) caused by lack of

iodide in the diet.

• Some amino acids are chemically modified

after incorporated into polypeptides. Ex.,

proline residue in collagen are oxidized to

form hydroxyproline residue.

III. Other amino acids and amino acid derivatives

• Glycosylation process that is addition

carbohydrate to molecules such as proteins.

• Many protein are phosphorylated by the

addition of phosphoryl groups to the side

chains of, serine, threonine or tyrosine.

• the oxidation of cysteine residue to form

cystine occurs after a polypeptide synthesized.

• 21st a.a, selenocysteine is found from serine

during protein synthesis and it is incorporated

into a few proteins in a wide variety of species.

• 22nd a.a is pyrrolysine, found in some species

of archae bacteria. Pyrrolysine modified from

lysine that is synthesized after being added to a

growing peptide by the translation