2.2.4.B. Amino Acids with Polar Neutral (Uncharged, Hydrophilic) Side Chain:

• Tyrosine is Phenylalanine with an extra hydroxyl (-OH) group attached. It is polar and very weakly acidic.  Tyrosine can play an important catalytic role in the active site of some enzymes. Reversible phosphorylation of –OH group in some enzymes is important in the regulation of  metabolic pathways.
• Serine and Threonine play important role in enzymes which regulate phosphorylation and energy metabolism.
• Cysteine has sulfur-containing side group.The group has the potential to be more reactive.It is not very polar.Cysteine is most important for its ability to link to another cysteine via the sulfur atoms to form a covalent disulfide bridge, important in the formation and maintenance of the tertiary (folded) structure in many proteins.
• Asparagine and Glutamine are the amide derivatives of Aspartate (Aspartic acid) and Glutamate (Glutamic acid) - see below.  They cannot be ionised and are therefore uncharged.

Figure 2.8: Structures of amino acids with uncharged hydrophilic side chain.

2.2.4.C. Amino Acids with Charged Side Chain:

1. Positively Charged R Groups
   • Lysine and Arginine both have pKs around 10.0 and are therefore always positively charged at neutral pH.
   • With a pK of 6.5, Histidine can be uncharged or positively charged depending upon its local environment.
   • Histidine has an important role in the catalytic mechanism of enzymes and explains why it is often found in the active site. 
2. Negatively (Nonpolar) Charged R Groups:
   • Two amino acids with negatively charged (i.e. acidic) side chains - Aspartate (Aspartic acid) and Glutamate (Glutamic acid). 
   • These amino acids confer a negative charge on the proteins of which they are part. 

Figure 2.9: Structures of amino acids with charged side chain.

2.2.4.D. "Special" 21st and 22nd Amino Acids:

Figure 2.10: Structures of 21st and 22nd natural amino acids