1. PTT103 BIOCHEMISTRY Amino Acids
Pn Khadijah Hanim Abdul Rahman

2. Introduction
Proteins - the most structural, sophisticated molecules known
- vary extensively in structure
- are polymer constructed from the same set of 20 amino acids
Polymer of amino acids = polypetides
Molecules with fewer than 50 amino acids = peptides
More than 50 amino acids = protein
Proteins consists of 1 or more polypeptides folded and coiled into specific conformations

4. Amino Acids structure
Amino Acids contain a central carbon atom (α-carbon) to which an amino group, a carboxylate group, a hydrogen atom and an R (side chain) group are attached

5. Amino acids shown in their prevailing ionic forms at pH7, approx pH within a cell

6. Name and three-letter
abbreviation of amino acid

7. The exception : proline differ from other standard amino acid
Its amino group is secondary
Formed by ring closure between R group and the amino nitrogen
Standard amino acid
(primary amino group)
Proline (secondary amino group)

8. Amino acid structure
The amino and carboxylic groups of amino acids readily ionized
At physiological pH (7)
- carboxyl group of an amino acid is unprotonated. conjugate base form (-COO-)
- amino group of an amino acid is protonated. in its conjugate acid form (+NH3)
Thus, each amino acid can behave as an acid or base
referred as amphoteric (substance that can act as acid or base)

9. The R group give each amino acid its unique properties
Neutral molecules which bear an equal number of positive and negative charges simultaneously are called zwitterions
The R group give each amino acid its unique properties
Structure of amino acid at pH7

10. Amino acid classes
Sequence of amino acids determines the three-dimensional configuration of each protein
Amino acids classified based on their capacity to interact with water
4 classes of amino acids :
a) neutral nonpolar (Gly, Ala, Val, Leu, Ile, Phe, Trp, Met, Cys, Pro)
b) neutral polar (ser, thr, tyr, asn, gln)
c) acidic (Asp, glu)
d) basic (lys, arg, his)

11. a) Neutral nonpolar amino acids
Term‘Neutral’ – contains hydrocarbon R groups- do not bear +ve or –ve charge
So they interact poorly with water and play important role in maintaining the three-dimensional structure of proteins
2 types of hydrocarbon R groups:
a) aromatic (contain cyclic structure that constitute a class of unsaturated hydrocarbons)
eg. Phenylalanine, tryptophan

13. b) aliphatic (nonaromatic hydrocarbon)
eg. Glycine, alanine, valine, leucine, isoleucine, proline, methionine, cysteine
Methionine & cysteine contain sulfur atom in the aliphatic side chain
In met, the nonbonding electrons of the sulfur atom can form bonds with electrophiles such as metal ions.
The nonpolar sulfhydryl group (-SH) of cys can form a weak H bond with O or N.
Sulfhydryl groups are highly reactive- important component in many enzymes.

14. b) Neutral polar amino acids
Polar amino acids = hydrophilic (water loving)
Have functional group capable of forming hydrogen bonding, so easily interact with water
Serine, threonine, tyrosine, asparagine, glutamine
Serine, threonine, tyrosine
- contain polar hydroxyl group (-OH)
- Thus enable them to from hydrogen bonding (important factor in protein structure)

16. Asparagine & glutamine
- are amide derivatives of aspartic acid and glutamic acid (acidic amino acids)
- amide funtional group are highly polar, so can form hydrogen bonding (effet on protein stability)

17. c) Acidic amino acids Contain carboxylate R group
The side chains of aspartic acid & glutamic acid are polar and negatively charged at physiological pH, so they often referred as aspartate and glutamate

19. d) Basic amino acids Lysine, Arginine, Histidine
Are polar and positively charge at physiological pH.
Therefore can form ionic bonds with acidic amino acids.
Lys contain amine R group which accepts a proton from water to form conjugate acid (-NH3+)
His is a weak base because it partially ionized at pH 7. His act as buffer. Important role in catalytic activity of enzymes.

21. Biologically active amino acids
The 20 standard amino acids undergo a bewildering number of chemical transformations.
Many amino acids are synthesizes not to be residues of polypeptides but to function independently.
Besides being components of protein, amino acids have several biological roles :
Chemical messengers
Precursors
Metabolite intermediates

22. Chemical messengers
- Neurotransmitters = substances released from one nerve cell that influence the function of a second nerve cell or a muscle cell
- Glycine
- γ-amino butyric acids
(derivative of glutamate),
- serotonin & melatonin
(derivative of tryptophan)

23. - Hormones = chemical signal molecules produced in one cell that regulate the function of other cells
- Thyroxine (tyrosine derivative), thyroid hormon secreted by thyroid gland
- Indole acetic acid (tryptophan derivative), is an auxin plant hormones. Stimulate growth of the root

24. Precursors
- a compound that participate in the chemical reaction to produces another compound
- amino acids are precursors of variety of complex nitrogen-containing molecules
- Nitrogenous base components of nucleotides and nucleic acids, chlorophyll

25. Metabolic intermediates
- several amino acids act as metabolic intermediates
- eg. Arginine, citrulline, ornithine (components of urea cycle)
- The synthesis of urea, a molecule formed in the livers- principle mechanism for disposal of nitrogenous waste

26. Amino acid stereoisomers
α-carbon of 19 amino acids attached to 4 diff. groups, referred as asymmetric/chiral carbons
Molecule with chiral carbon, can exist as stereoisomers
Stereoisomers
- isomeric molecule that have the same molecular formula
- but differ only in the three-dimensional orientations of their atoms in space.

27. They are known as enantiomers of one another
Molecules with chiral carbon are not superimposable on their mirror image in the same way that a left hand is not superimposable on its mirror image, a right hand
They are known as enantiomers of one another
L-Alanine and D-Alanine are mirror image to one another

28. Glyceraldehyde is the reference compound for optical isomers (to differ between L and D)

29. Most asymmetric molecules found in living organisms only occur in only 1 stereoisomeric form, either D or L.
Chirality has had a profound effect on the structural and functional properties of biomolecules
For eg: the right-handed helices result from the presence of L-amino acids.
In addition, because enzymes are chiral molecules, they only bind substrate molecules in one enantiomeric form.
Proteases, enzyme that degrade proteins by hydrolyzing peptide bonds, cannot degrade polypeptides composed of D-amino acids.

30. Question
Certain bacterial species have outer layers composed of polymers made of D-amino acids. Immune system cells, whose task is to attack and destroy foreign cells, cannot destroy those bacteria. Suggest a reason for this phenomenon.

31. Titration of amino acids
Amino acids contain ionizable group
the predominant ionic form of amino acids in solution depends on pH
Titration of amino acid :
- illustrate the effect of pH on amino acids structure
- a useful tool in determining the reactivity of amino acid side chains

32. Upon titration with base, it act as an acid (donate proton)
when amino acid is dissolved in water, it exist predominantly in the isoelectric form (no net charge and electrically neutral)
Upon titration with base, it act as an acid (donate proton)
Upon titration with acid, it act as a base (accept proton)
+H3N-CH2-COO- + HCl +H3N-CH2-COOH + Cl-
(base) (acid) (1)
+H3N-CH2-COO- + NaOH H2N-CH2-COO- + Na+ +H2O
(acid) (base) (2)

33. Titration of alanine
Consider alanine, a simple amino acid contain 2 titrable groups
During titration with strong base, NaOH, alanine loses 2 protons.
In a strongly acidic sol (pH 0), ala present mainly in the form of in which the carboxyl group is uncharged.

34. At this point, alanine net charge = +1, because ammonium group is protonated.
Lowering of the H+ conc results in the COOH group losing a proton to become COO-.
At this point, ala has no net charge and electrically neutral.
The pH at which this occur is called the isoelectric point (pI)
Because no net charge at pI, amino acids are least soluble at this pH.
The pI for ala may be calculated as: pI = pK1 + pK2 2

36. pK1 and pK2 of alanine are 2.34 and 9.7.
The pI value for alanine :
pI = = 6
As the titration continues, the ammonium group will lose its proton, leaving an uncharged amino group
This molecule has a net –ve charge because of the carboxylate group. 2

37. Amino acid reactions
The functional groups of organic molecules determine which reactions they may undergo.
Amino acids with their COOH groups, amino groups and various R groups can undergo numerous chemical reactions.
i.e peptide bond & disulfide bridge formation (effect protein structure)

38. Peptide bond formation
Polypeptides are linear polymers composed of amino acids linked together by peptide bonds
Peptide bonds are amide linkage (CO-NH) formed when the carboxyl group of one amino acid react with amino group of another amino acid

40. This reaction is a dehydration (mol. water is removed)
So, the linked amino acids are referred to as amino acid residues.
When two amino acid molecules are linked, the product is called a dipeptide.
eg. Serine and glycine can form dipeptides glycylserine or serylglycine

41. As amino acids are added and the chain lengthens, the prefix reflect the number of residues
eg. Tripeptides contain three amino acid residues

42. Amino acid residue with the free amino group is called the N-terminal residue and is written to the left
Amino acid residue with free carboxyl group is called C-terminal residue and is written to the right
Peptides are named by using their amino acid sequence,
start from their N-terminal residue
eg. Alanylglycylphenilalanine

43. Cysteine oxidation The sulfhydryl group of cysteine is highly reactive
Common reaction = reversible oxidation that form disulfide
Two molecules of cysteine oxidized to form a cystine (molecule that contain disulfide bond)
When 2 cys residues form such bond, it is referred to as a disulfide bridge.
Disulfide bridges help to stabilize many polypeptides and proteins.