Med103 Amino Acid Structures, Classification, and Reactions 2024-2025 Fall PDF

Amino Acid Structures, Classification and Reactions MED103 The Cell 2024-2025 Fall Assist. Prof. Dr. Onur BULUT Department of Medical Biochemistry School of Medicine Atılım University Learning Objectives Understand the Structure of Amino Acids: Identify the basic structure of an amino acid and...

Amino Acid Structures, Classification and Reactions MED103 The Cell 2024-2025 Fall Assist. Prof. Dr. Onur BULUT Department of Medical Biochemistry School of Medicine Atılım University Learning Objectives Understand the Structure of Amino Acids: Identify the basic structure of an amino acid and explain the role of each component. Distinguish Between D- and L-Isomers: Recognize the difference between D- and L-amino acids and their relevance in biological systems. Classify Amino Acids: Categorize amino acids based on their side chains into nonpolar, polar, acidic, and basic groups. Explain Acidic and Basic Properties: Describe how amino acids behave as acids or bases depending on pH. Understand Amino Acid Titration: Explain how amino acids are titrated and the significance of their pKa values. OVERVIEW Proteins: abundant and diverse molecules in life. Essential for Life Processes: Enzymes & hormones regulate metabolism Contractile proteins enable movement Collagen supports bone structure Vital Functions in Blood Hemoglobin & albumin transport molecules Immunoglobulins fight infections Common Structure: Linear polymers of amino acids STRUCTURE OF AMINO ACIDS Diversity & Genetic Code: Over 300 amino acids exist in nature. 20 amino acids coded by DNA are used in mammalian proteins. Structure & Charge at Physiologic pH: Each amino acid has a carboxyl group (-COO⁻), a primary amino group (-NH₃⁺), and a unique R-group. Peptide Linkages & Side Chains: Carboxyl and amino groups form peptide bonds, limiting reactivity The R-group (side chain) defines the amino acid's role and properties (polar or nonpolar). Structural features of amino acids Amino Acid Substituents four substituents: a carboxyl group an amino group a hydrogen atom an R group (a side chain unique to each amino acid) glycine has a second hydrogen atom instead of an R group The Amino Acid Residues in Proteins are L-Stereoisomers Chiral α-Carbon: Attached to four different groups, making amino acids optically active. Exception: Glycine (two hydrogens, optically inactive). D and L Forms (Stereoisomers): Mirror images, also known as enantiomers. Proteins only contain L-amino acids. D-amino acids found in some antibiotics, plant, and bacterial cell walls. Amino Acids Can Be Classified by R Group Five main classes: nonpolar, aliphatic (7) aromatic (3) polar, uncharged (5) positively charged (3) negatively charged (2) A. Nonpolar amino acids: Each of these amino acids has a nonpolar side chain. Do not gain/lose protons or form hydrogen/ionic bonds. "Oily" or lipid-like, promoting hydrophobic interactions. Location of nonpolar amino acids in proteins: In proteins found in aqueous solutions: Nonpolar side chains cluster inside the protein. Driven by the hydrophobic effect, like oil droplets in water. Helps stabilize the protein's 3D shape. In Hydrophobic Environments (e.g., Membranes): Nonpolar side chains are on the Location of nonpolar outside, interacting with lipids. amino acids in soluble and membrane proteins B. Aromatic amino acids: R groups absorb UV light at 270–280 nm. Can contribute to the hydrophobic effect. Absorption of ultraviolet light by aromatic amino acids. Comparison of the light absorption spectra of the aromatic amino acids tryptophan, tyrosine, and phenylalanine at pH 6.0. The amino acids are present in equimolar amounts (10−3 M) under identical conditions. The measured absorbance of tryptophan is more than four times that of tyrosine at a wavelength of 280 nm. Note that the maximum light absorption for both tryptophan and tyrosine occurs near 280 nm. Light absorption by phenylalanine generally contributes little to the spectroscopic properties of proteins. C. Polar uncharged amino acids: These amino acids have zero net charge at neutral pH. R groups can form hydrogen bonds. Cysteine can form disulfide bonds. The polar OH group of serine and threonine can serve as a site of attachment for structures such as a phosphate group. Disulfide bonds in proteins: Formation Two cysteine side chains (–SH) oxidize to form cystine with a disulfide bond (–S–S–). Role in Protein Stability Stabilizes many extracellular proteins (e.g., albumin). Important for maintaining protein structure and enzyme active sites. D. Positively charged amino acids: These amino acids have significant positive charge at pH 7.0. D. Negatively charged amino acids: These amino acids have significant negative charge at pH 7.0. ACIDIC AND BASIC PROPERTIES OF AMINO ACIDS Weak Acids and Bases: Amino and carboxyl groups, and some R groups, can act as weak acids/bases. Zwitterions at Neutral pH: Amino acids without ionizable R groups exist as zwitterions (dipolar ions) in water. Zwitterions can act as both acids and bases (amphoteric).  Ampholytes: Amino acids with dual acid-base nature, termed ampholytes. Example: A simple monoamino monocarboxylic α-amino acid, such as alanine, is a diprotic acid when fully protonated; it has two groups, the —COOH group and the —NH3+ group, that can yield protons: Titration of an Amino Acid cation ⇌ zwitterion ⇌ anion Acid-Base Titration of Glycine Two Ionizable Groups Carboxyl group (pK₁ = 2.34) and amino group (pK₂ = 9.60) Titration Stages First Stage: Carboxyl group (-COOH) loses a proton At midpoint (pH 2.34), equal amounts of proton donor and acceptor forms Second Stage: Amino group (-NH₃⁺) loses a proton At midpoint (pH 9.60), glycine is mainly in zwitterion form (dipolar ion) Titration Curve Features Inflection points at pK₁ and pK₂ where pH = pKa values of the groups The pH at which the net electric charge is zero is the isoelectric point (pI). Information from a Titration Curve 1. pKa Values Provides quantitative pKa values for glycine's ionizable groups: Carboxyl group (-COOH): pKa = 2.34 Amino group (-NH₃⁺): pKa = 9.60 2. Buffering Regions Two buffering zones where glycine resists changes in pH: Near pH 2.34: Buffering around the -COOH group Near pH 9.60: Buffering around the -NH₃⁺ group Not an effective buffer at physiological pH (~7.4). 3. Application of Henderson-Hasselbalch Equation Can calculate the ratio of proton-donor to proton- acceptor forms within glycine's buffering ranges. buffer regions  Isoelectric Point, pI for amino acids without ionizable side chains, the isoelectric point (pI) is: pK1  pK 2 pI  2 pH = pI = net charge is zero (amino acid least soluble in water, does not migrate in electric field) pH > pI = net negative change pH < pI = net positive charge Amino Acids Differ in Their Acid-Base Properties Amino acids with a single amino group, carboxyl group, and non-ionizable R group (e.g., glycine) have similar titration curves and pKa values. Differences in pKa values reflect the chemical environment of the R group. Amino acids with ionizable R groups have more complex titration curves, with three stages and three pKa values. The isoelectric point (pI) depends on the ionizing R group: Glutamate: pI = 3.22 (due to two carboxyl groups). Histidine: pI = 7.59 (due to amino and imidazole groups). Titration of Amino Acids with an Ionizable R Group