Amino Acids

Acid-Base Chemistry with Buffers

Question: What is the final pH when 10 mL of 1M HCl is added to 1L of 0.1M phosphate buffer at pH 7.2? Understand how strong acids like HCl affect buffer solutions. Consider the buffer capacity and the ability of the phosphate buffer to resist changes in pH.

Further Inquiry into Buffers

Next Class Question: What is the final pH when 10 mL of 1M HCl is added to 1L of 0.01M phosphate buffer at pH 7.2? Note the difference in phosphate buffer concentration in this scenario. Explore how buffer capacity varies with concentration.

Structure of Amino Acids

Ionizable Functional Groups: Amino acids contain both NH3 (amino) and COOH (carboxylic acid) groups.

Ionization States: COO- (deprotonated form) contributes to net charge. NH3+ (protonated form) as well.

Zwitterionic Form: At physiological pH, amino acids typically exist in a zwitterionic form (both positive and negative charges).

Titration of Amino Acids

Titration Curves: Used to determine pKa values of amino acids. Example: Glycine has pK1 = 2.34 and pK2 = 9.60. Important for understanding how amino acids behave in different pH conditions.

pKa Values of Amino Acids

Key Properties: Contains data on pKa values, characteristic hydropathy index, and occurrence in proteins. Example Amino Acids: Glycine: pK1 = 2.34, pK2 = 9.60, is hydrophilic with occurrence rates. Cysteine: Special properties due to the presence of sulfur, allowing for disulfide bridge formation.

Isoelectric Point (pI)

Definition: pH where amino acid or protein has no net charge. Important for protein solubility and stability.

Calculation of Isoelectric Point

Determining pI: Find the pKa values defining the neutral form. Example Calculation for Glutamic Acid: pI = (pK1 + pKR)/2, Results in pI = (2.19 + 4.25)/2 = 3.22.

Characteristics of Amino Acids

Building Blocks of Proteins: Amino acids vary in size, shape, charge, H-bonding capability, hydrophobicity, and chemical reactivity.

Generalized Structure of Amino Acids

Zwitterion Nature at Physiological pH: Amino group and carboxylate group make them behave as dipolar ions. Titration Curves: Each amino acid possesses unique titration characteristics due to its R group.

Chirality of Amino Acids

Optical Activity: All amino acids (except one) are chiral. Living Systems: Only “L” configuration amino acids are present in biological organisms.

Importance of Stereoisomerism

Enzyme Specificity: Active sites of enzymes are stereospecific; they react preferentially with one enantiomer. Relevance in Pharmacology: Understanding chirality is crucial for drug design and effectiveness.

One-Letter Codes for Amino Acids

There are 20 Common Amino Acids: Each amino acid is represented by a single-letter code; crucial to memorize these for biochemical studies.

pKa Relationships in Amino Acids

Amino acids exhibit associated pKa values for their functional groups (NH2/NH3+, COO-/COOH). Some amino acids have additional pKa values for their R groups (pKR).

Non-Polar R Groups

R groups range from hydrophobic to very hydrophobic, affecting protein structure and organization. Methionine plays a role due to its sulfur content.

Characteristics of Aromatic R Groups

Hydrophobic Nature: Amino acids with aromatic R groups are typically found buried in the interior of proteins.

Polar but Uncharged R Groups

Amino acids like Serine, Threonine, and Cysteine can make hydrogen bonds but do not ionize in neutral pH.

Charged Amino Acids

Basic (Positively Charged): Lysine, Arginine, and Histidine have R groups that are ionized at physiological pH, making them hydrophilic. Acidic (Negatively Charged): Aspartate and Glutamate also have ionized R groups.

Identifying Acidic Amino Acids

Visual Representation: Diagrams illustrating the ionization state of amino acids showcasing acidic nature.

Quiz Question - Tryptophan

What is the one-letter code for Tryptophan? a) T b) W c) F d) K

Quiz Question - One-Letter Code K

Which amino acid corresponds to code K? a) Arginine b) Glycine c) Lysine d) Kerosine

Ionizable Groups in Amino Acids

Ionization States: NH3 and COOH groups can ionize, affecting the net charge at various pH levels.

Special Case - Cysteine

Disulfide Bond Formation: The sulfur atom in cysteine can form covalent bonds, important for the three-dimensional structure of proteins.

Special Case - Histidine

Imidazole Ring: The R group of histidine can be ionized at near physiological pH, with implications on protein function.

Formation of Polypeptides

Peptide Bonds: Amino acids are linked by peptide bonds to form polypeptides via condensation reactions (release of water).

Nomenclature of Polypeptides

Designations of amino acid chains: Dipeptide: Two amino acids. Tripeptide: Three amino acids. Polypeptide: Chains of 2-100 amino acids. Protein: Chains of over 100 amino acids.

Polypeptide Directionality

N to C Terminus: Amino acids are sequenced from the N-terminus (free amino group) to the C-terminus (free carboxyl group).

Polypeptides as Polyprotic

Multiple Ionizable Groups: Affect the net charge at different pH levels. pI Calculation: Changes in pH can adjust ionization states of functional groups in peptides.

Peptide Bond Characteristics

Rigidity: Peptide bonds exhibit partial double-bond character, limiting rotation and affecting protein structure. Trans Configurations: Trans conformation is favored due to reduced steric clashes.

Isomerization at Proline

Cis and Trans Configurations: Prolines can adopt cis configurations in certain structural contexts, facilitated by proline isomerases.

Types of Proteins

Protein Structures: Classifications based on chain number and solubility (monomeric, dimeric, oligomeric, globular, fibrous). Conjugated Proteins: Contain additional chemical groups.

Determining Primary Structure

Methods: Enzymatic digestion and DNA sequence inference. Edman Degradation: Identifies amino acids one by one; less effective for larger proteins.

Rotation in Peptide Bonds

Bond Rotation: Not all bonds allow free rotation; secondary structure depends on permissible bond angles.

Ramachandran Plot

Structure Visualization: Shows permissible angles for amino acids; used to understand secondary structure conformations.

Exceptions in Ramachandran Plots

Glycine and Proline Variations: Glycine allows more flexibility in angles, while proline is more constrained in its conformational space.