Amino Acids and Protein Chemistry

Amino Acids

• The building blocks of proteins.
• Only 20 of the 500 naturally occurring amino acids are found in the human body and coded for by DNA.
• Contain an acidic carboxyl group (-COOH), a basic amino group (-NH2), and a unique side chain (R group) that distinguishes them.
• Most are α-amino acids, with the amino group attached to the α-carbon atom.
• Classified by side chain properties: hydrophobic (nonpolar), uncharged hydrophilic (polar), and charged hydrophilic (polar).
• In aqueous solutions, nonpolar amino acid side chains cluster in the protein's interior.
• Exhibit optical activity, existing as D and L isomers; proteins use primarily L-α-amino acids.
• Each has an isoelectric point (pI), the pH at which it exists as a zwitterion (electrically neutral).

Protein Chemistry

• Proteins are polymers of amino acids linked by peptide bonds.
• Peptide bonds are formed between the α-carboxyl group of one amino acid and the α-amino group of the next.
• Peptide bonds are broken by enzymatic hydrolysis and are resistant to denaturation.
• A polypeptide chain has an amino (N)-terminal and a carboxyl (C)-terminal end.

Protein Structure

• Primary structure: The linear sequence of amino acids in a polypeptide chain.
• Secondary structure: The arrangement of amino acids in space; includes α-helices and β-pleated sheets, stabilized by hydrogen bonds. α-helices have 3-4 amino acids per turn. β-sheets comprise extended polypeptide chains linked by hydrogen bonds.
• Tertiary structure: The three-dimensional folding of a single polypeptide chain, stabilized by disulfide bonds, hydrophobic interactions, hydrogen bonds, and ionic interactions. Monomeric proteins have only tertiary structure.
• Quaternary structure: The arrangement of multiple polypeptide subunits in a protein; polymeric proteins exhibit this level of structure. Subunits are held together by noncovalent interactions.

Protein Misfolding

• Can result from spontaneous events, gene mutations, or abnormal proteolytic cleavage.
• Leads to the accumulation of insoluble protein aggregates, potentially causing diseases like Alzheimer's, type II diabetes, and Parkinson's.

Protein Denaturation

• Unfolding of a protein, disrupting secondary, tertiary, and quaternary structures without breaking peptide bonds.
• Caused by physical factors (heat, UV radiation) and chemical factors (strong acids, alkalis, heavy metals).
• Results in loss of biological activity and is often irreversible. However, sometimes this process is used beneficially in food preparation or sterilization.

Protein Properties

• Many proteins are water-soluble but insoluble in nonpolar solvents. Some are exceptions.
• Amphoteric properties: Contain both free carboxyl and amino groups, allowing them to act as buffers. This is crucial for maintaining blood pH. Histidine plays a significant role.

Protein Classification

• Simple proteins: Yield only amino acids upon hydrolysis. Examples include albumins, globulins, histones (basic proteins), and scleroproteins (water-insoluble structural proteins like collagen, elastin, and keratin).
• Conjugated proteins: Contain amino acids and a non-protein prosthetic group. Examples include phosphoproteins (e.g., casein) and glycoproteins.