1. Chapter: 6 Amino acids Dr. Gobinath Pandian

2. INTRODUCTION
Amino acids are molecules containing an amine group (NH), a carboxylic acid group (COOH) and a side chain(R) that varies between different amino acids. These molecules contain the key elements of carbon, hydrogen, oxygen, and nitrogen.

3. Any of a class of organic compounds in which a carbon atom has bonds to an amino group (-NH2), a carboxyl group (-COOH), a hydrogen atom (-H), and an organic side group (called -R).
Amino acids are organic compounds made of carbon, hydrogen, oxygen, nitrogen, and (in some cases) sulfur bonded in characteristic formations.
They are therefore both carboxylic acids and amines. The physical and chemical properties unique to each result from the properties of the R group, particularly its tendency to interact with water and its charge (if any).
Amino acids joined linearly by peptide bonds (see covalent bond) in a particular order make up peptides and proteins.

4. Amino acids are critical to life, and have many functions in metabolism. One particularly important function is to serve as the building blocks of proteins, which are just linear chains of amino acids, or more precisely, amino acid residues.
Every protein is chemically defined by the order of amino acid residues, their primary structure and this, in turn, determines their secondary structure

6. Glycine is the smallest of the amino acids
Glycine is the smallest of the amino acids. It is ambivalent, meaning that it can be inside or outside of the protein molecule. In aqueous solution at or near neutral pH, glycine will exist predominantly as the zwitterion
The isoelectric point or isoelectric pH of glycine will be centered between the pKas of the two ionizable groups, the amino group and the carboxylic acid group.
In estimating the pKa of a functional group, it is important to consider the molecule as a whole. For example, glycine is a derivative of acetic acid, and the pKa of acetic acid is well known. Alternatively, glycine could be considered a derivative of aminoethane.

7. Cysteine is one of two sulfur-containing amino acids; the other is methionine. Cysteine differs from serine in a single atom-- the sulfur of the thiol replaces the oxygen of the alcohol.
The amino acids are, however, much more different in their physical and chemical properties than their similarity might suggest.
Cysteine also plays a key role in stabilizing extracellular proteins. Cysteine can react with itself to form an oxidized dimer by formation of a disulfide bond.
The environment within a cell is too strongly reducing for disulfides to form, but in the extracellular environment, disulfides can form and play a key role in stabilizing many such proteins, such as the digestive enzymes of the small intestine.

8. Methionine, an essential amino acid, is one of the two sulfur-containing amino acids. The side chain is quite hydrophobic and methionine is usually found buried within proteins.
Unlike cysteine, the sulfur of methionine is not highly nucleophilic, although it will react with some electrophilic centers. It is generally not a participant in the covalent chemistry that occurs in the active centers of enzymes.
Methionine as the free amino acid plays several important roles in metabolism. It can react to form S-Adenosyl-L-Methionine (SAM) which servers at a methyl donor in reactions .

9. Alanine is a hydrophobic molecule. It is ambivalent, meaning that it can be inside or outside of the protein molecule. The α carbon of alanine is optically active; in proteins, only the L-isomer is found.
Note that alanine is the α-amino acid analog of the α-keto acid pyruvate, an intermediate in sugar metabolism. Alanine and pyruvate are interchangeable by a transamination reaction.

10. Asparagine is the amide of aspartic acid
Asparagine is the amide of aspartic acid. The amide group does not carry a formal charge under any biologically relevant pH conditions. The amide is rather easily hydrolyzed, converting asparagine to aspartic acid.
Asparagine has a high propensity to hydrogen bond, since the amide group can accept two and donate two hydrogen bonds.
Asparagine is a common site for attachment of carbohydrates in glycoproteins.

11. Aspartic acid is one of two acidic amino acids
Aspartic acid is one of two acidic amino acids. Aspartic acid and glutamic acid play important roles as general acids in enzyme active centers, as well as in maintaining the solubility and ionic character of proteins.
Proteins in the serum are critical to maintaining the pH balance in the body; it is largely the charged amino acids that are involved in the buffering properties of proteins.
Aspartic acid and oxaloacetate are interconvertable by a simple transamination reaction, just as alanine and pyruvate are interconvertible.

12. Glutamine is the amide of glutamic acid, and is uncharged under all biological conditions.
The additional single methylene group in the side chain relative to asparagine allows glutamine in the free form or as the N-terminus of proteins to spontaneously cyclize and deamidate yielding the six-membered ring structure pyrrolidone carboxylic acid, which is found at the N-terminus of many immunoglobulin polypeptides. This causes obvious difficulties with amino acid sequence determination.

13. Histidine, an essential amino acid, has as a positively charged imidazole functional group.
The imidazole makes it a common participant in enzyme catalyzed reactions.
The unprotonated imidazole is nucleophilic and can serve as a general base, while the protonated form can serve as a general acid. The residue can also serve a role in stabilizing the folded structures of proteins.

14. Isoleucine, an essential amino acid, is one of the three amino acids having branched hydrocarbon side chains. It is usually interchangeable with leucine and occasionally with valine in proteins.
The side chains of these amino acids are not reactive and therefore not involved in any covalent chemistry in enzyme active centers.
However, these residues are critically important for ligand binding to proteins, and play central roles in protein stability. Note also that the β carbon of isoleucine is optically active, just as the β carbon of threonine. These two amino acids, isoleucine and threonine, have in common the fact that they have two chiral centers.

15. Leucine, an essential amino acid, is one of the three amino acid with a branched hydrocarbon side chain.
It has one additional methylene group in its side chain compared with valine.
Like valine, leucine is hydrophobic and generally buried in folded proteins.

16. Lysine. an essential amino acid, has a positively charged ε-amino group (a primary amine).
Lysine is basically alanine with a propylamine substituent on theβcarbon. The ε-amino group has a significantly higher pKa (about 10.5 in polypeptides) than does the α-amino group.
The amino group is highly reactive and often participates in a reactions at the active centers of enzymes. Proteins only have one α amino group, but numerous ε amino groups

17. Phenylalanine, an essential amino acid, is a derivative of alanine with a phenyl substituent on the β carbon. Phenylalanine is quite hydrophobic and even the free amino acid is not very soluble in water.
Due to its hydrophobicity, phenylalanine is nearly always found buried within a protein. The π electrons of the phenyl ring can stack with other aromatic systems and often do within folded proteins, adding to the stability of the structure.

18. Proline shares many properties with the aliphatic group.
Proline is formally NOT an amino acid, but an imino acid. Nonetheless, it is called an amino acid. The primary amine on the α carbon of glutamate semialdehyde forms a Schiff base with the aldehyde which is then reduced, yielding proline.
When proline is in a peptide bond, it does not have a hydrogen on the α amino group, so it cannot donate a hydrogen bond to stabilize an α helix or a β sheet. It is often said, inaccurately, that proline cannot exist in an α helix. When proline is found in an α helix, the helix will have a slight bend due to the lack of the hydrogen bond.

19. Serine differs from alanine in that one of the methylenic hydrogens is replaced by a hydroxyl group.
Serine is one of two hydroxyl amino acids. Both are commonly considered to by hydrophilic due to the hydrogen bonding capacity of the hydroxyl group.

20. Threonine, an essential amino acid, is a hydrophilic molecule.
Threonine is an other hydroxyl-containing amino acid. It differs from serine by having a methyl substituent in place of one of the hydrogens on the β carbon and it differs from valine by replacement of a methyl substituent with a hydroxyl group.
Note that both the α and β carbons of threonine are optically active.

21. Tryptophan, an essential amino acid, is the largest of the amino acids
Tryptophan, an essential amino acid, is the largest of the amino acids. It is also a derivative of alanine, having an indole substituent on the β carbon.
The indole functional group absorbs strongly in the near ultraviolet part of the spectrum. The indole nitrogen can hydrogen bond donate, and as a result, tryptophan, or at least the nitrogen, is often in contact with solvent in folded proteins.

22. Tyrosine, an essential amino acid, is also an aromatic amino acid and is derived from phenylalanine by hydroxylation in the para position.
While tyrosine is hydrophobic, it is significantly more soluble that is phenylalanine. The phenolic hydroxyl of tyrosine is significantly more acidic than are the aliphatic hydroxyls of either serine or threonine, having a pKa of about 9.8 in polypeptides.
As with all ionizable groups, the precise pKa will depend to a major degree upon the environment within the protein.
Tyrosines that are on the surface of a protein will generally have a lower pKa than those that are buried within a protein; ionization yielding the phenolate anion would be exceedingly unstable in the hydrophobic interior of a protein.

23. Valine, an essential amino acid, is hydrophobic, and as expected, is usually found in the interior of proteins.
Valine differs from threonine by replacement of the hydroxyl group with a methyl substituent. Valine is often referred to as one of the amino acids with hydrocarbon side chains, or as a branched chain amino acid.
Note that valine and threonine are of roughly the same shape and volume. It is difficult even in a high resolution structure of a protein to distinguish valine from threonine.   

24. Glutamic acid has one additional methylene group in its side chain than does aspartic acid. The side chain carboxyl of aspartic acid is referred to as the β carboxyl group, while that of glutamic acid is referred to as the γ carboxyl group.
The pKa of the γ carboxyl group for glutamic acid in a polypeptide is about 4.3, significantly higher than that of aspartic acid.
In some proteins, due to a vitamin K dependent carboxylase, some glutamic acids will be dicarboxylic acids, referred to as γ carboxyglutamic acid, that form tight binding sites for calcium ion.

25. Arginine, an essential amino acid, has a positively charged guanidino group. Arginine is well designed to bind the phosphate anion, and is often found in the active centers of proteins that bind phosphorylated substrates.
As a cation, arginine, as well as lysine, plays a role in maintaining the overall charge balance of a protein.
There are 6 codons in the genetic code for arginine, yet, although this large a number of codons is normally associated with a high frequency of the particular amino acid in proteins, arginine is one of the least frequent amino acids.
The discrepancy between the frequency of the amino acid in proteins and the number of codons is greater for arginine than for any other amino acid.

26. Non-polar amino acids
They have equal number of amino and carboxyl groups and are neutral.
These amino acids are hydrophobic and have no charge on the 'R' group. The amino acids in this group are alanine, valine, leucine, isoleucine, phenyl alanine, glycine, tryptophan, methionine and proline.

27. Non-polar amino acids

28. Polar amino acids with no charge
These amino acids do not have any charge on the 'R' group. These amino acids participate in hydrogen bonding of protein structure.
The amino acids in this group are - serine, threonine, tyrosine, cysteine, glutamine and aspargine

29. Polar amino acids with no charge

30. Polar amino acids with positive charge
Polar amino acids with positive charge have more amino groups as compared to carboxyl groups making it basic.
The amino acids, which have positive charge on the 'R' group are placed in this category. They are lysine, arginine and histidine.

31. Polar amino acids with negative charge
Polar amino acids with negative charge have more carboxyl groups than amino groups making them acidic.
The amino acids, which have negative charge on the 'R' group are placed in this category. They are called as dicarboxylic mono-amino acids. They are aspartic acid and glutamic acid.

32. Types of Amino acids
Aromatic group
Aliphatic group
Sulphur Containing amino acids
Hydrophylic amino acids
Aromatic amino acids are normally hydrophobic and includes phenylalanine, tyrosine and tryptophan.
Aliphatic amino acids are basically hydrophobic and an be located in core of protein. glycine ,valine, alanine, leucine, proline and isoleucine are aliphatic amino acids.
sulphur containing amino acids include sulphur atom and cysteine and methionine are the examples.

33. Hydrophilc amino acids are further categorized as acidic ,neutral and basic amino acids. Acidic amino acids are highly polar and are always negatively charged. Aspartate and glutamate are the examples.
Basic amino acids contains side chains that are positively charged . lysine,arginine and histidine are the examples.
Neutral amino acids are polar in nature and serine ,threonine, asparagine and glutamine are the examples.