Amino Acids 2

Biochemistry Overview

  - Course: CHEM 2713
  - Instructor: Dr. Amitabh Jha
  - Institution: Acadia University

Amino Acids

  - Essential topics: Structure, Properties, Characterization, Titration, Stereochemistry, Peptides, Proteins

Studying Amino Acids

  - Investigate correlation between protein function and molecular structure.
  - Complex proteins are comprised of combinations of 20 simple amino acids.
  - Proteins are classified based on the polarity of their side chains.

Titration of Amino Acids

  - The predominant ionic form of the ionizable groups in amino acids depends on pH levels.
  - Seven standard amino acids possess ionizable side chains:
    - Aspartic acid (Asp)
    - Glutamic acid (Glu)
    - Histidine (His)
    - Lysine (Lys)
    - Arginine (Arg)
    - Tyrosine (Tyr)
    - Cysteine (Cys)
  - These amino acids are sensitive to pH changes.

Titration and Ionization

  - Titration is essential for determining the relative ionization potential of acidic and basic side chain groups in amino acids or peptides.
  - The pH at which amino acids and proteins show no net charge is identified as the isoelectric point (pI).
  - Amino acids with ionizable side chains exhibit more complex titration curves.

Example: Titration of Glutamic Acid

  - At low pH, glutamic acid carries a +1 charge.
  - As base is added, the alpha-carboxyl group loses a proton, leading to a change in charge.
  - Final net charge may drop to -2 upon complete titration.
  - pKa Values for Glutamic Acid:
    - $pK_{a1} = 2.19$
    - $pK_{a2} = 9.67$
    - $pK_{aR} = 4.25$

Biologically Active Amino Acids

  - Roles of amino acids:
    1. Some amino acids or their derivatives function as chemical messengers:
        - Neurotransmitters: e.g. tryptophan derivative serotonin.
        - Hormones: e.g. tyrosine derivative thyroxine.
    2. Precursors for complex nitrogen-containing molecules such as nucleotides and heme.
    3. Serve as metabolic intermediates (e.g., arginine, ornithine, and citrulline in the urea cycle).
       - Urea cycle converts toxic ammonia into urea for excretion.

Modified Amino Acids in Proteins

  - Some proteins contain amino acids modified post-synthesis:
    - Phosphorylation occurs on serine, threonine, and tyrosine.
    - Modified residues include:
        - $ext{𝛾-Carboxyglutamate}$ (found in prothrombin)
        - $ext{4-hydroxyproline}$ and $ext{5-hydroxylysine}$ (found in collagen, the most abundant protein in connective tissue).

Amino Acid Stereoisomers

  - Molecules with chiral carbons can exist as stereoisomers that differ in spatial arrangement of atoms.
  - The alpha-carbon (a chiral carbon) is attached to four distinct groups, allowing for stereoisomerism.
  - Exception: Glycine, which is the only non-chiral (achiral) standard amino acid.

Chirality in Biological Compounds

  - A significant number of biological compounds are chiral.

Definitions of Stereoisomers

  - Enantiomers (optical isomers): Chiral compound and its mirror image.
  - Enantiomers exhibit identical physical properties except in the way they rotate plane polarized light.
  - Configuration Assignments:
    - Using the R/S system for each chiral carbon’s configuration.
    - Using the D/L system for biomolecules.
  - Most asymmetric biomolecules exist in only one stereoisomeric form, typically either D or L.
  - L-amino acids principally found in proteins, with few exceptions.

Cahn-Ingold-Prelog Priority Rules

  - E and Z Nomenclature: Follow Cahn-Ingold-Prelog (CIP) sequence rules to assign priorities based on:
    1. Atomic number: Higher atomic number = higher priority.
    2. Atomic weights: If atomic numbers are similar, prioritize based on atomic weights.

D/L Designation of Molecules

  - Molecules are designated as D or L depending on their similarity of arrangement around the asymmetric carbon relative to glyceraldehyde.

Practical Applications and Exercises

  - Identify the stereochemical configuration of the alpha-carbon in phenylalanine using Cahn–Ingold–Prelog priority rules.
  - Practice problems illustrate configuration checking for:
    - Serine
    - Leucine
    - Tyrosine

Implications of Stereochemistry

  - The pharmaceutical industry is concerned with stereochemistry:
  - Many drugs are synthesized as racemic mixtures (both R and S enantiomers).
  - However, typically, only one enantiomer has the desired biological activity (e.g., Ibuprofen, Thalidomide).

Amino Acid (Peptide/Protein) Visualization Techniques

  - Amino-terminus labeling: Ninhydrin is commonly used in forensic science for detecting latent fingermarks, reacting with amino acids to produce a dark purple product known as Ruhemann’s purple.

Questions?

  - Open for discussion and inquiries regarding the presented material.