Overview
This lecture introduces amino acids, peptides, and proteins, covering their structure, classification, chemical properties, and levels of protein structure, as well as denaturation. These topics are foundational for understanding biochemistry on the MCAT.
Classification and Structure of Amino Acids
- Proteins are made from 20 standard alpha amino acids, each with a central (alpha) carbon, amino group, carboxyl group, hydrogen, and unique R group.
- Amino acids can be grouped as nonpolar (hydrophobic), polar uncharged, aromatic, acidic (negatively charged), or basic (positively charged).
- Nonpolar amino acids (e.g., glycine, alanine, valine, leucine, isoleucine, proline, methionine) are generally found inside proteins.
- Aromatic amino acids absorb UV light; examples are phenylalanine, tyrosine, and tryptophan.
- Polar uncharged amino acids (e.g., serine, threonine, asparagine, glutamine, cysteine) can form hydrogen bonds.
- Acidic amino acids (aspartate, glutamate) have negatively charged side chains at physiological pH.
- Basic amino acids (lysine, arginine, histidine) possess positively charged side chains at physiological pH.
- Amino acids are chiral (except glycine) and mostly have the S configuration (except cysteine, which is R).
Acid-Base Chemistry of Amino Acids
- Amino acids are amphoteric, acting as acids or bases depending on pH.
- At low pH: fully protonated (net positive charge); at neutral pH: zwitterion (no net charge); at high pH: fully deprotonated (net negative charge).
- Each amino acid has at least two pKa values (carboxyl ~2, amino group ~9-10); some have a third pKa if side chains are ionizable.
- The isoelectric point (pI) is calculated by averaging relevant pKa values.
- Titration curves show how amino acids gain/lose protons and their buffer regions.
Peptide Bond Formation and Hydrolysis
- Peptide bonds link amino acids via a condensation (dehydration) reaction, forming water.
- The N-terminus (free amino group) and C-terminus (free carboxyl group) define peptide direction.
- Peptide bonds can be broken by hydrolysis (addition of water), catalyzed chemically or by enzymes.
Levels of Protein Structure
- Primary structure: linear sequence of amino acids from N- to C-terminus.
- Secondary structure: local folding patterns (alpha helices, beta sheets) stabilized by hydrogen bonds in the backbone.
- Proline often disrupts secondary structures and introduces turns.
- Tertiary structure: 3D folding driven by side chain interactions (hydrophobic, hydrogen, ionic, and disulfide bonds).
- Quaternary structure: arrangement of multiple polypeptide chains into a functional complex.
- Conjugated proteins have prosthetic groups (non-protein components) essential for function.
Protein Denaturation
- Denaturation disrupts tertiary and quaternary structure, causing loss of function but usually leaves primary structure intact.
- Causes include heat and chemical agents (e.g., detergents, urea).
- Denaturation is often irreversible, except in mild cases.
Key Terms & Definitions
- Amino Acid — Building block of proteins; contains amino, carboxyl, hydrogen, and R group.
- Zwitterion — Molecule with both positive and negative charges but overall neutral.
- Peptide Bond — Covalent bond between amino acids, formed via condensation reaction.
- Primary Structure — Sequence of amino acids in a protein.
- Secondary Structure — Local folding of the polypeptide chain (alpha helix, beta sheet).
- Tertiary Structure — Complete 3D folding of a single polypeptide.
- Quaternary Structure — Arrangement of multiple polypeptide chains.
- Denaturation — Loss of protein’s structure and function due to disruption of interactions.
Action Items / Next Steps
- Memorize the names, structures, three-letter, and one-letter codes for all 20 amino acids.
- Review acid-base chemistry fundamentals and practice drawing amino acid titration curves.
- Study the different types of protein structure and be able to recognize examples.
- Prepare for questions on protein denaturation mechanisms and consequences.