Amino acids are the units of proteins, and understanding its chemistry and the the properties assists in understanding the functions of proteins. This gives in an idea to why a certain protein behaves in a certain way.

1. Chemistry of Amino Acids(AᾹs)

2. Amino Acids
What are amino acids ??
Amino acids are organic compounds.
Organic compounds are the substances that
are made up of Hydrocarbon (Hydrogen and
Carbon) and its derivatives.

3. Contents
• Definition
• History
• General Structure
• Classification
• Properties
– Physical
– Isomerism
– Optical activity and stereoisomerism
– Spectroscopic property of amino acid
– Iso-electric point
– Chemical Reactions
– Color reactions
• Biosynthesis
• Catabolism
• Separation and analysis of amino acid mixture
• Functions
• References

4. Definition
The basic monomeric structural unit of
proteins organic in nature whose
constituent are two functional groups, an
amino group (-NH2) which is basic in
nature and a carboxylic group (-COOH)
which is acidic in nature are called as
amino acids.

5. History
1700
1750
1800
1850
1900
1950
1806, Asparagine
was isolated by
Pierre-Jean Robiquet
and Louis Nicolas
Vauquelin from
asparagus juice.
1935, Threonine
William
Cumming Rose
1819, Leucine
from cheese
1820, Glycine by Henri Braconnot
from gelatin by acid hydrolysis
1922, J H
Muller and
Odake found
Methionine
1849, Justus von
Leibig found
tyrosine form
cheese
1904, Isoleucine
by Ehrlich
1901, Valine by Emil
Fischer from caesin
and tryptophan by
Fredrick Hopkins
from pancreatic
digest of caesin
1850, Alalnine by Adolph
Strecker from
acetaldehyde
1900, Proline
by Willstatter
1896, Histidine
by Albert Kossel
& Sven Hedin
1889, Lysine by
Drechsel isolated
it from casein
1886, Arginine by
Ernst Schulze from
lupine seedling
1865, Serine by
Cramer from Silk
1866, Glutamic acid
fromwheat gluten
by Karl Ritthausen
1883, Cysteine
and Glutamine by
Schulze from
beet juice
1879, Phenylalanine from
Lupinus Zuteus seedling
by Schulze & Barbeiri
1868, Aspartic
acid from
legume in plant
seed

6. General Structure of an Amino Acid
Amino group Hydrogen Side-chain
Carboxylic group
α Carbon

7. Classification
A. Based on structure
B. Based on metabolic fate
C. Based on side chain characters
D. Based on nutritional requirement

8. A. Based on structure
1. Aliphatic amino acids
a) Monoamino monocarboxylic acid
i. Simple AĀs - Gly, Ala.
ii. Branched chain AĀs – Val, Ile, Leu.
iii. Hydroxy AĀs – Ser, Thr.
iv. Sulphur containing AĀs – Cys, Met.
v. AĀs with amide group – Asn, Gln.
b) Monoamino dicarboxylic acid – Asp, Glu.
c) Dibasic monocarboxylic acid – Lys, Arg.
2. Aromatic AĀs – Phe, Tyr.
3. Heterocyclic AĀs – Trp, His.
4. Imino acids – Pro, hydroxyproline
5. Derived AĀs
a) Derieved AĀs found in protein – hydroxyproline, hydroxylysine
b) Derieved amino acids not seen in proteins – ornithine, citrulline, homocysteine.
c) Non alpha AĀs – GABA.

9. B. Based on metabolic fate
1. Purely Ketogenic
 Leu.
 Sometimes Lys is also considered
2. Ketogenic & Glucogenic
 Lys, Ile, Phe, Tyr, Trp.
3. Purely Glucogenic
 All the remaining 14.

10. C. Based on side chain Characters
1. Hydrophilic or polar AĀs
 Charged hydrophilic
 -vely charged – Asp, Glu
 +vely charged – Lys, Arg, His
 Uncharged hydrophilic
 Thr, Ser with OH side chain
 Asn, Gln with amide side chain
 Cys with SH side chain
 Gly with hydrogen also considered

11. 2. Hydrophobic or non polar AĀs
 Hydrophobic with aliphatic side chain
 Val, Ala, Ile, Leu
 Hydrophobic with aromatic side chain
 Phe, Tyr, Trp
C. Based on side chain Characters

12. D. Based on nutritional requirement
1. Essential/Indispensable
 Ile, Leu, Thr, Lys, Met, Phy, Trp, Val.
2. Semi-essential
 His, Arg
3. Non-essential
 Remaining 10

13. alanine valine
leucine
isoleucine
proline
phenylalanine tyrosine
tryptophan methionine serine threonine

14. cysteine
asparagine glutamine
aspartate
glutamate
lysine
histidine

15. Properties
Physical
– Colourless, crystalline substances
– Taste
• Sweet: Gly, Ala, Val, Ser, Trp, His & Pro.
• Tasteless: Leu.
• Bitter: Ile & Arg.
• Artificial sweetener: Aspartame contains Asp & Phy.
– Melting point: above 200˚C.
– High dielectric constant
– Solubility
• Water: mostly all.
• Alcohol(polar solvent): mostly all.
• Benzene(non-polar solvent): none.
• Tyr is soluble in hot water.
defined as the product of
magnitude of charge & distance
of separation between the
charges.

16. • Asymmetric carbon
• Chirality
• Enantiomer
• Stereoisomerism
• Plane polarised light
• Zwitterion

17. Isomerism
• Of the standard α- AĀs, all but Gly can exist in either of two optical
isomers, called L or D AĀs, which are mirror images of each other.
• L-amino acids represent all of the AĀs found in proteins
• D- AĀs are found in some proteins
– as in exotic sea-dwelling organisms such as cone snails,
– are also abundant components of the peptidoglycan cell walls of
bacteria,
– D-serine may act as a neurotransmitter in the brain.
• The isomers are of two types
– Optical isomer

18. Optical activity and stereochemistry of amino acids
– With the exception of Gly, all the 19 other common AĀs
have a uniquely different functional group on the central
tetrahedral alpha carbon(α-C)
– The α-C is termed "chiral" to indicate there are four
different constituents and that the α-C is asymmetric
– Since the α-C is asymmetric there exists two possible,
non-superimposable, mirror images of the amino acids

19. The D, L system
•When looking down the H-Ca bond towards the α-C there is a
mnemonic to identify the L-enantiomer of Aās
•L-enantiomer, CORN.
•CONR (a silly, meaningless word) for the D-enantiomer.

20. Stereoisomerism of Amino Acids
Levo-
rotatory
Dextro-
rotatory

21. • Enantiomeric molecules have an optical
property known as optical activity - the
ability to rotate the plane of plane polarized
light
• Clockwise: dextrorotatoy
• Counterclockwise: levorotatory
•All common AĀs are the L-enantiomer
•However, not all AĀs are Levorotatory, some are actually Dextrorotatory with
regard to their optical activity
•To (attempt) to avoid confusion, the optical activities are given as (+) for
dextrorotatory, and (-) for levorotatory
•L(+)-alanine
•L(-)-serine

22. Spectroscopic properties of AĀs
• This refers to the ability of AĀs to absorb or emit electromagnetic energy at
different wavelengths (i.e. energies)
• No AĀs absorb light in the visible spectrum (i.e. they are "colorless").
• All AĀs absorb in the IR (longer wavelengths, weaker energy than visible light)
• Some AĀs absorb in the UV spectrum (shorter wavelengths, higher energy than
visible light)
– Absorption occurs as electrons rise to higher energy states
– Electrons in aromatic ring structures absorb in the UV. spectrum. Such
structures comprise the side chains of Trp, Tyr & Phy.

23. Isoelectric point
• Isoelectric point (pI) is the pH at which a particular molecule or surface carries no
net electrical charge or the negative(-ve) and positive(+ve) charges are equal.
• Zwitterions contain both +ve and -ve charges depending on the functional group.
• Net charge on the molecule is affected by pH of their surrounding & can become
more +vely or -vely charged d/t loss or gain of protons (H+).
Calculating pI values
• For an AĀs with only one amine and one carboxyl group, the pI can be calculated
from the mean of the pKas of this molecule.

24. Glycine has two
ionizable groups: a
COOH group and NH2
group, with pKa values
of 2.34 and 9.6
respectively.
pI =(2.34+9.6)/2 = 5.97

25. • For simple AĀs such as Ala, the pI is an average of the pKa's of
the carboxyl (2.34) and ammonium (9.69) groups.
• Thus, the pI for Ala is calculated to be: (2.34 + 9.69)/2 = 6.02.
• In the case of Asp, the similar acids are the alpha-carboxyl
function (pKa = 2.1) and the side-chain carboxyl function (pKa
= 3.9), so pI = (2.1 + 3.9)/2 = 3.0.
• For Arg, the similar acids are the guanidinium species on the
side-chain (pKa = 12.5) and the alpha-ammonium function
(pKa = 9.0), so the calculated pI = (12.5 + 9.0)/2 = 10.75.

26. Chemical Reactions
A. Reactions due to –COOH group
1. Decarboxylation.
• Histidine Histamine +CO2
• Tyrosine Tyramine + CO2
• Lysine Cadavarine + CO2

27. 2. Formation of amides
• -COOH group of dicarboxylic AĀs can combine with ammonia to from the
corresponding amide.
• Aspartic acid + NH3 Asaparagine
3. Reduction to amino alcohol
• Achieved in presence of lithium aluminium hydride
4. Formations of esters
• Can form esters with alcohols
• The –COOH group can be esterfied with alcohol
• Treatment with Na2CO3 solution in cold releases free ester from ester
hydrochloride.

28. B. Reactions due to –NH2 group
1. Transamination
• α amino group of AĀ can be transferred to α keto acid to form
new AĀ and α keto acid.
• Important reaction in the synthesis of non essential AĀ.
amino acid
α-keto acid Amino acid
α-keto acid

29. Fig:
Oxidative
deamination
2. Oxidative deamination
• α amino group is removed from the AĀ to
form corresponding keto acid and ammonia.
• In body glutamic acid is the most common AĀ
to undergo oxidative deamination

30. 3. Formation of carbamino compound
• Carbondioxide adds to α amino group of AĀs to form
carbamino compound.
• Occurs at alkaline pH
• Serves as the mechanism for transport of CO2 from tissues to
lungs by Hb.

31. C. Reactions due to side chain
1. Transmethylation
• The methyl group of Met, after activation, may be transferred
to an acceptor which becomes methylated
• Met + acceptor methylated acceptor +
homocystiene

32. 2. Ester formation by OH group
• The hydroxy AĀs can form ester with phosphoric acid
• Ser & Thr are involved in the formation of phosphoprotein
• Similarly, these hydroxl group can form O-glycosidic bonds with
carbohydrate residues to form glycoprotein.
3. Reaction of the amide group
• The amide group of Gln & Asn can form N-glycosidic bond with
with carbohydrate residues to form glycoproteins.
4. Reaction of SH group
• Cys has a sulfhydryl(SH) group & it can form a disulphide bond
(S-S)with another Cys residue
• The two Cys residue can connect two polypeptide chain by the
formation of interchain disulphide bonds & links.
• The dimer formed by the two Cys residue is called cystine or
Dicysteine.

33. D. Peptide bond formation
– Mistakenly called amino bond
– covalent bond
– formed b/w 2 molecules when the carboxyl group of
one molecule reacts with the amino group of the
another molecule, releasing a molecule of H2O.
– resulting CO-NH bond is the peptide bond, & resulting
mol is an amide.
– peptide bond c/b broken down by hydrolysis
– peptide bonds formed within proteins have tendency to
break when subjected to the +nce of H2O (metastable
bonds)
Peptide bond Elimination
of water

34. E. Property due to both –COOH group and –NH2 group
• Formation of chelated co-ordination complexes with certain
heavy metals and other ions
• These include Cu++, Co++, Mn++ & Ca++.
• O=C-O -O-C=O
Ca++
H2C-NH2 NH2-CH2
• chelates are non ionic –used to remove calcium from bones
and teeth

35. Color reaction of AᾹs
• Ninhydrin reaction
– Adopted for qualitative & quantitative estimation
– Used for detection of AᾹs in chromatography
– AᾹs + 2 mols. Of Ninhydrin aldehyde with 1 C atom
less + color complex
– Color complex: pink/ purple/ blue (c/a Ruhemann’s purple)
– Pro, hydroxy-Pro – yellow
– Gln, Asn(AᾹs with amide group) – brown
• Xanthoproteic test
– Nitration rxn undergone by concņ HNO3
– Rings in Phe, Tyr & Trp
– End product yellow, intensified by alkaline medium
– Rxn causes the yellow stain in skin by HNO3

36. • Millon’s test
– Phenol group of tyrosine + HgSO4
H2SO4+NaNO3
red color mercuric phenolate
– HgNO3/Hg(NO3)2 in HNO3 c/b used
– Cl- interferes with the rxn so not suitable for tyrosine in
urine samples
– Tapoica(deficient in Phe & Tyr) give –ve Millon’s &
Xanthoproteic test
• Sakaguchi’s test for Arg:
– Arg + α-napthol + alk. Hypobromite bright red
color
– This is d/t guanidium group

37. • Aldehyde test for Trp:
– Hopkins-Cole test:
• Trp + glyoxylic acid (mix)
• Mix layered over H2SO4
• Violet ring at interface shows the +nce of indole ring
– Acree-Rosenheim rxn:
• Formaldehyde & HgSO4 is used
– Ehrlich’s rxn:
• Para-dimethyl-amino-benzaldehyde & strong HCl
• Gives dark blue color
• Gelatin with limited Trp content do not give this test
• Pauly’s test for His/Tyr:
– Diazo-benzene sulfonic acid + imidazole group of His
alkaline condition
Diazotised product (cherry red color)
– Gives orange red color with phenol

38. • Sulphur test for Cys:
– Cys boiled with strong alkali: organic S splits & forms
Na2S, which on addition of Pb-acetate produces PbS(
black ppt)
– Met doesn’t give this test as S in Met is in thio-ester
linkage which is difficult to break

39. Biosynthesis
• Nitrogen is first assimilated into organic compounds in the
form of glutamate, formed from alpha-ketoglutarate and
ammonia in the mitochondrion.
• In order to form other AĀs, transaminase is used to move
the amino group to another alpha-keto carboxylic acid.
• Eg, aspartate aminotransferase converts glutamate and
oxaloacetate to alpha-ketoglutarate and aspartate.

40. •Nonstandard AĀs are usually formed through
modifications to standard AĀs.
•Eg, Homocysteine is formed through the transsulfuration
pathway or by the demethylation of methionine via the
intermediate metabolite S-adenosyl methionine.
•Hydroxyproline is made by a posttranslational
modification of proline.
•Microorganisms and plants can synthesize many
uncommon AĀs.

41. Catabolism
• AĀs can be:
– Glucogenic
– Ketogenic
– Both glucogenic and ketogenic

42. • Degradation of AĀs often involve deamination by moving
its amino group to alpha-ketoglutarate, forming glutamate.
• This process involves transaminases, often the same as
those used in amination during synthesis.
• In many vertebrates, the amino group is then removed
through the urea cycle and is excreted in the form of urea.

44. Separation & analysis of AᾹs mixtures
The 20 common AĀs differ from one another in
several important ways. Here are just two:
• Mass
• Isoelectric point
• In looking at the isoelectric point of the different AĀs it
seems that they will have different partial charges at a
given pH.
• Eg, at pH 6.0 some will be -vely charged, and some +vely
charged.

45. •For those that are -vely charged, some will be slightly -ve,
and others strongly -ve. Similarly, for those that are +vely
charged, some will be slightly +ve, and others strongly +ve
•The charge differences of the AĀs means that they will
have different affinities for other cationic or anionic
charges

46. Ion Exchange Chromatography :
• Basis
• If the immobile surface was coated with anions, then the
chromatography would be termed "cation exchange" chromatography
(and cations would selectively bind and be removed from the solution
flowing through).

47. • Strength of binding can be affected by pH & salt
concn of the buffer. The ionic species "stuck" to the
column can be removed & collected by changing
one of these conditions.

48. • We could lower the pH of the buffer & protonate anions,
this would eliminate their electrostatic attraction to the
immobilized cation surface.
• Or, we could ↑se the salt concentration of the buffer, the
anions in the salt would "compete off" bound anions on
the cation surface.

49. Amino acid 3 & 1
letter
abbvtn
Mol.
weight
Molecular
formula
Melting
point
(◦C)
Properties
Leucine Leu/L 131 C6H13NO2 293 Production of GH
Tyrosine Tyr/Y 181 C9H11NO3 290 ↑ses NTs, DOPA & NE
Production of T3,T4,TSH
Phenylalanine Phe/F 165 C9H11NO2 273 Formation of Ep
Arginine Arg/R 174 C6H14N4O
2
223 Precursor of nitric oxide
Lysine Lys/K 146 C5H14N2O
2
210 Treatment of HSV

50. Histidine His/
H
155 C6H9N3O
2
285 Released in allergic rxn
Valine Val/V 117 C5H11NO
2
315 Important in smooth nervous
functioning
Tryptophan Trp/
W
182 C11h12N2
O2
283 Production of serotonin
Isoleucine Ile/I 131 C6H13NO
2
287 Isomer of leucine
Methionine Met/
M
149 C5H11NO
2S
284 Helps reduce the estrogen load
prevents Ca

51. Amino
acid
3 & 1
letter
abbvtn
Molecula
r weight
Molecular
formula
Melting
point
Properties
Threonine Thr/T 119 C4H9NO3 256 Elevates symptoms of multiple
sclerosis
Proline Pro/P 115 C5H9NO2 228 Diminishes arteriosclerosis
Glutamine Gln/Q 146 C5H10N2
O3
185 Protects GI lining
Releases cortisol
Neurotoxic effect & cancer
prevention
Cysteine Cys/C 121 C3H7NO2
S
220 Produces GSH & Taurine
Recovery of hair & nail ts.
Aspartic
acid
Asp/D 133 C4H7NO4 270 Participates in ornithine cycle
Imp in function of RNA/DNA

52. Glutami
c acid
Glu
/E
147 C5H9N
O4
205 Supports brain function
Acts as NTs
Serine Ser/
S
105 C3H7N
O3
222 Production of Abs
Absorption of creatine
Alanine Ala
/A
63 C3H7N
O2
315 Helps treat benign prostrate
hyperplasia
Glycine Gly
/G
57 C2H5N
O2
233 Protection against cancer by
antioxidants
⅓ of collagen are glycine
Aspara
gines
Asn
/N
132 C4H8N2
O3
235 Biosynthesis of glycoproteins

53. Selenocysteine :
• The 21st amino acid
• Abbreviated as Sec or U
• +nt in enzymes (eg glutathione peroxidases, tetraiodothyronine 5'
deiodinases, glycine reductases)
• has a structure similar to that of cysteine, but with an atom of
selenium taking the place of the usual sulfur, forming a selenol group.
• Proteins contain one or more selenocysteine residues are called
selenoproteins
• encoded in a special way by UGA codon, which is normally a stop
codon.

54. Pyrrolysine:
• abbreviated as Pyl or O
• is a naturally occurring, genetically coded amino acid used
by some methanogenic archaea.
• It is similar to lysine, but with an added pyrroline ring linked
to the end of the lysine side chain.
• Produced by a specific tRNA and aminoacyl tRNA
synthetase, it forms part of an unusual genetic cod
• is considered the 22nd proteinogenic amino acid.
• encoded in mRNA by the UAG codon

55. Functions
• Over 300 AĀs +nt & only 22 found in human body.
• Tyr forms hormones such as T3, T4, TSH, Ep, NE &
pigment melanin
• Trp can synthesise Niacin
• Gly, Arg & Met can synthesise creatine
• Gly & Cys
– helps in synthesis of bile salts
– Used as detoxicants

56. • Glu, Cys & Gly synthesise glutathione
• His changes to histamine on decarboxylation
• Serotonin is formed from Trp
• Gly is used in synthesis of heme
• Met acts as active methionine & helps in transmethylation
• Cys & Met are sources of sulphur
• Asp & Gln for pyramidine synthesis
• Asn & Glu for purine synthesis

57. References:
1. Biochemistry by DM Vasudevan,Sreekumari S, 4th edition.
2. Tietz Fundamentals of Clinical Chemistry, 6th edition by Carl A. Burtis,
Edward R. Ashwood, and David E. Bruns, editors. St Louis.
3. Devlin's Textbook of Biochemistry,4th Edition by Thomas M Devlin.
4. Textbook of biochemistry by Satyanarayana, 4th edition.
5. Garrett & Grisham, Biochemistry, 4th edition.
6. Textbook Of Medical Biochemistry, Jaypee, Mn Chatterjee, Rana
Shinde.
7. Biochemistry by Pankaja Naik, Pankaja, Ph.D. Jaypee, 3rd edition.
8. World wide web.

58. To hold, as it were the mirror up to nature.
-William Shakespeare
Thank You