Biology of Amino Acids and Proteins

Biological Functions of Proteins

• Proteins have many important biological functions, including:
  • Enzymes: increase the rate of reaction by a factor of 1 billion
  • Carriers: hemoglobin, transferrin
  • Receptors: hormones, cytokines
  • Transport: membrane channels
  • Structure: collagen, elastin
  • Protective: immunoglobulins
  • Contractile: muscle, cytoskeleton
  • Regulatory: hormones, govern metabolic pathways

Amino Acids (aa) and Proteins

• There are over 300 amino acids found in nature, but only 20 are found in mammalian proteins and are coded for by DNA
• The nature of the side chain decides the role of an amino acid in a protein
• Amino acids can be classified according to the properties of their side chains
• Amino acids can function as an acid (donate H+) or as a base (accept H+)

Amino Acid Structure

• At physiological pH, an amino acid has a carboxyl group (-COO-) and an amino group (-NH3+)
• There are two forms of an amino acid: neutral and zwitterionic
• Zwitterion: a neutral molecule with equal numbers of + and - charges
• Isoelectric point: the pH at which there is no net charge on the zwitterion

α-Amino Acids

• Only 20 are common in nature
• All 20 are α-amino acids
• Alpha means the amine is adjacent to the carboxy group on the α-C
• Amino acids differ by their R groups
• 19 out of the 20 are stereoisomers

Classes of Amino Acids

• Amino acids are classified based on the polarity of their side chains:
  • Non-polar, hydrophobic
  • Polar, neutral
  • Negatively charged
  • Positively charged

Hydrophobic, Non-polar Amino Acids

• Non-polar amino acids don't bind or give off protons or participate in hydrogen or ion bonds
• They are "oily" or lipid-like material
• Hydrophobic amino acids do not "like" to reside in an aqueous (water) environment
• In aqueous solutions, hydrophobic amino acids tend to cluster together in the interior of the hydrophobic core of the protein or within the lipid portion of the membrane
• The hydrophobic interaction is important in stabilizing protein structure

Hydrophilic, Polar Amino Acids

• Uncharged side chains
• These amino acids have zero net charge at neutral pH
• Some side chains act as sites of attachment for compounds
• The -OH of serine and threonine can be linked to oligosaccharide in glycoprotein

Hydrophobic vs. Hydrophilic Amino Acids

• Within the membrane: nonpolar amino acids, hydrophobic, anchors protein into the membrane
• On outer surfaces of membrane in fluid: polar amino acids, hydrophilic, extend into extracellular fluid and into the cytosol

Charged Amino Acids

• Negatively charged amino acids: acidic R group
• Positively charged amino acids: basic R group

Positively Charged Amino Acids

• These amino acids have a positive charge at neutral pH
• These amino acids are proton acceptors at neutral pH
• Histidine has an important role in the catalytic mechanism of enzymes

Negatively Charged Amino Acids

• These amino acids have a negative charge at neutral pH
• These amino acids are proton donors at neutral pH
• Contain carboxyl-groups that are weaker acids than the α-carboxyl-group

Disulfide Bond Formation

• Two cysteines (each contains a sulfhydryl group -SH) in proximity will form a covalent bond
• The two –SH form a dimer “cystine” containing a covalent cross-link disulfide bond (disulfide bridge, or dicysteine bond)
• Significantly stabilizes tertiary structure (e.g. antibodies/immunoglobulins)
• Important component of the active site at many enzymes

Amino Acids - Summary

• 10 amino acids not synthesized by the body:
  • Met, Ile, Leu, Val, Phe, Trp, Thr, Arg, His, Lys
• Must be obtained from the diet

Structural Features of Amino Acids

• All 20 are α-amino acids
• For 19 of the 20, the α-amino group is primary; for proline, it is secondary (imino acid)
• Except glycine, the α-carbons for 19 of them are asymmetric (or chiral)