Alpha-Amino Acids and pH

α-Amino Acids

• Essential amino acids cannot be synthesized and must be obtained through diet
• The 8 essential amino acids are: Valine (Val), Leucine (Leu), Isoleucine (Ile), Threonine (Thr), Methionine (Met), Phenylalanine (Phe), Tryptophan (Trp), and Lysine (Lys)
• Non-essential amino acids are not required in the diet, as the body can synthesize them
• There are 12 non-essential amino acids

Amino Acids and pH

• At pH 7, the COOH group of an amino acid ionizes to COO- and the NH2 group ionizes to NH3+
• At pH 7 amino acids exist as dipolar ions, carrying both a positive and a negative charge, also known as zwitterions
• Carboxylate ion structure is COO-
• Ammonia's structure is NH3+
• Ionization is when an atom or molecule gains a negative or positive charge by gaining or losing electrons, often with chemical changes

Roles of Amino Acids

• Amino acids determine protein structure and function through their nature and sequence
• Amino acids act as energy substrates like glucose, fatty acids, and ketones
• Amino acids are precursors to vital biological molecules, including purine and pyrimidine
• Glutamine transmits nervous impulses

Classifying Amino Acids

• Some α-amino acids constitute proteins, and some do not
• Some amino acids have their amine group in a position other than the α position
• An example of an amino acid with the amine group not in the α position is γ-aminobutyric acid
• The chemical structure of γ-aminobutyric acid is H2N-CH2-CH2-CH2-COOH

Classifying Alpha-Amino Acids In Proteins

• Alpha-amino acids that constitute proteins are classified by the structure of their lateral chain R
• They are also classified by the polarity of the lateral chain R
• The structure of the lateral chain (R) may be aliphatic or cyclic

Aliphatic Chain Structures

• Aliphatic hydrocarbon chains can be linear, such as glycine (glycocoll) and alanine, or branched, such as valine, leucine, and isoleucine
• Aliphatic alcohol functional groups include serine and threonine
• Aliphatic sulfur functional groups include cysteine and methionine
• Aliphatic acidic functional groups and their amide derivatives consist of aspartic acid and asparagine, as well as glutamic acid and glutamine
• Aliphatic basic functional groups include lysine, arginine, and histidine

Cyclic Chain Structures

• Aromatic cyclic chains include phenylalanine, tyrosine, and tryptophan
• Imino-acid cyclic chains include proline

Polarity of Lateral Chains

• Polar amino acids include non-ionizable molecules such as serine, threonine, asparagine, glutamine, cysteine, and tyrosine
• Polar amino acids include ionizable molecules such as aspartic acid, glutamic acid, lysine, arginine, and histidine
• Non-polar amino acids include glycine, alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, and proline

Polarity and Ionization

• The longer the lateral chain R, the less polar the amino acid becomes
• Cyclic aromatic structures decrease the solubility of the amino acid
• Functional groups like OH and NH2 increase polarity, while thiol groups decrease polarity
• The ionization of amino acids is pH-dependent

Aliphatic Amino Acids

• Glycine, also known as Glycocoll, contains no asymmetric carbon
• Glycine confers extreme flexibility to the polypeptide chain
• Alanine is a superior homologue of glycine
• The branched lateral chain in valine, leucine, and isoleucine is relatively rigid
• Branched chains play an important role in the tertiary structures of proteins

Aliphatic Amino Acids with Alcohol Functional Group

• The hydroxyl group in alcohol functional groups can form hydrogen bonds with water molecules or other amino acids of the polypeptide chain
• Free electrons on the oxygen atom of the hydroxyl group can attack positively charged groups, which has a catalysing role
• Serine and threonine are important sites for post-translational modification
• Post-translational modification controls the activity of several enzymes and proteins by reversible phosphorylation

Aliphatic Amino Acids & Amide Derivatives

• Asp (aspartic acid) and Glu (glutamic acid) play important roles in transamination reactions
• Asn (asparagine) and Gln (glutamine) transport and store nitrogen in plants and animals

Aliphatic Amino Acids and Basic Functional Groups

• Hydroxylation of lysine turns it into 5-hydroxylysine through post-translational modification
• In invertebrates, arginine-phosphate stores energy similar to creatine phosphate in vertebrates
• Histidine contains an imidazole ring, so may be categorized with heterocyclic amino acids

Bonds In Amino Acids

• Hydrogen bonding occurs in amino acids with polar non-ionisable lateral chains
• Ionic bonding occurs in amino acids with polar ionisable lateral chains
• Hydrophobic bonding occurs in amino acids with non-polar aliphatic chains
• Van der Waals bonding may occur in the lateral chains of all amino acids

Stereoisomers and Enantiomers

• All amino acids except glycine have an asymmetric α carbon atom bonded to four different groups: -H, -NH2, -COOH, and –R (lateral chain)
• Because of this asymmetrical carbon atom, two stereoisomers exist: D and L amino acids, based on the location of the NH2 group
• D and L amino acids are considered enantiomers

Enantiomers and Light

• Enantiomers share the same physical and chemical properties but differ in biological properties based on optical activity
• One enantiomer rotates linearly polarized light to the right, known as dextrorotatory (+), and is the configuration of most amino acids
• The other enantiomer rotates linearly polarized light to the left, known as levorotatory (-)
• In D and L series amino acids, rotational capacity does not predict direction of polarization
• The rotational capacity largely depends on the pH

Ionization of Amino Acids

• Zwitterions are electrically charged and electrically neutral with positive and negative charges
• The net charge on a zwitterion molecule is zero
• Zwitterions have minimal water solubility at pHi and form aggregates because they lack charge to repel each other
• Zwitterions cannot perform electrophoresis

Neutral Amino Acids and Ionization

• Neutral amino acids lack supplementary ionisable groups in their lateral chain
• At the pk of an ionisable functional group, equal amounts of ionisable and non-ionisable molecules exist
• At pkCOOH, there is 50% COOH and 50% COO-
• At pkNH2, there is 50% NH2 and 50% NH3+
• Can calculate the isoelectric point (pHi) using the formula: pHi=(pKCOOH+ pKNH2)/2

Acidic Conditions:

• pKa, pH, and the concentrations of protonated and deprotonated forms of an acid (HA) are related by the equation: pH = pKa + log10 ([A-]/[HA])

pH Gradients

• If pH is less than pK1, the cationic form of the amino acid predominates
• If pH equals pK1, the concentrations of cations and neutral molecules are equal
• If pH is equal to (pK1 + pK2)/2, the neutral form predominates, and pH is equal to the pHi
• If pH is greater than pK2, the anionic form predominates

Ionization Constants

• For neutral amino acids:
  • pKCOOH = 2
  • pKNH2 = 10
  • At pH 7, both the –COOH and -NH2 groups are ionized, resulting in a net charge of 0
• For amino acids containing a supplementary ionisable group:
  • For aspartate, the lateral pKCOOH = 4
  • For lysine, the lateral pKNH2 = 12

Peptide Bondage

• The α-carboxylic and α-amine functional groups are engaged in peptide bonds in polypeptide chains
• The charge of proteins mainly depends on the charge of the lateral chains of basic and acidic amino acids

Protein Overview

• All proteins consist of 20 amino acids, and the number of possible combinations is unlimited, represented by 20n for n amino acids
• Proteins are polymers of amino acids linked by amide bonds known as peptide bonds
• The peptide bond is formed between the α-carboxylic group of one amino acid and the α-amine group of another
• The length of a peptide chain can be represented as: Peptide = (a.a)n

Structural Formula of Polypeptide Chain

• Polypeptide chain structural formulas start with a zigzag, a free amino group on the left and a free carboxylic acid group the right
• Place the Cα, CO, and N atoms
• Places the lateral chains (R) on the Cα atoms

Fibrous Proteins

• Fibrous proteins have an elongated, thread-like shape and are typically insoluble in water
• Collagen is an example found in the ECM of connective tissues; it provides tensile strength to bones, tendons, skin, and cartilage
• Keratin is an example found in hair, nails, and the outer layer of skin; it provides mechanical strength and protection
• Elastin is an example found in tissues that require elasticity, like the skin, blood vessels, and lungs

Globular Proteins

• Globular proteins are spherical or globular in shape
• Globular proteins are usually soluble in water
• Globular proteins are involved in many biochemical processes

Derived Proteins

• Derived proteins are those that have been modified from fibrous or globular proteins

Simple and Complex proteins

• Simple proteins contain only amino acids with no other chemical groups or molecules
• Simple proteins break down by hydrolysis to constituent amino acids

Conjugated Proteins

• Conjugated proteins contains non-protein components

Protein Structure

• The structure of proteins can be organized into primary, secondary, tertiary, and quaternary levels

Primary Structure

• The peptide bond in the primary structure of proteins is an amide linkage between the α-carboxyl group of one amino acid and the α-amino group of another
• Peptide bonds form with the elimination of a water molecule between the carboxylic group of the first amino acid and the amino group of the second amino acid

Polypeptide Chains

• Peptide chains are not broken by chemical processes such as heating or high concentrations of urea, which denature proteins
• A primary protein structure is determined by the gene encoding it
• Primary structure alterations from the gene results in changes to secondary and tertiary structure, and can cause malfunctions or non-functionality

Superior Structures

• Proteins obtain specific conformations in their superior structures
• Secondary structures are the spatial interaction acid residues in the chains linked by Hydrogen bonds C=O and N-H groups
• Tertiary structures involve spatial interactions between distant acids in single chains; they are maintained by hydrogen, hydrophobic, ionic, and van der Waals forces, as well as disulfide bonds between the lateral chains of the amino acid residues

Protein Quaternary Structures

• Quaternary Protein Structures involve spatial interaction polypeptide chains supported by hydrogen, hydrophobic, ionic, and van der Waals bonds
• Globular proteins adopt secondary, tertiary, or quaternary structures, but fibrous proteins have only secondary structures

Secondary Structures

• Secondary structures are a spatial configuration of protein sequences of 10 to 30 amino acids within a polypeptide chain
• Globular proteins possess several structures, and fibrous only one
• Bond angles have repetitive values
• Structures are stabilized with hydrogen bonds between –CO and –NH groups in peptide bonds located at regular intervals within

Alpha-Helix Structures

• The polypeptide chain twists around a virtual axis, excluding the lateral chains
• The helix has chirality, being either right-handed or left-handed
• A helix can be characterized by the number, n, of peptide units per helical turn, and by its pitch, p, the distance of each turn rising along its axis
• Between 0 and 100% of αhelices are found in proteins with keratin's αhelix being located in hair

Helix Formation

• Stabilized structures use intrachain hydrogen bonds creating oxygen atoms of C=O and hydrogen atoms in N–H groups
• There are always three amino acid residues between bonds
• Hydrogen bonds are internal and acids are external.
• Helix structure uses L amino acid residues with tension angles
• Comprises 35 acid residues from a dozen tours

Beta-Sheet Structures

• Beta-sheets consist of beta strands connected laterally with 2 or 3 backbone hydrogen bonds forming a twisted, pleated sheet
• Beta strands can vary but composed usually of 3 to 10 amino acids
• Consist of 2 beta strands fragmented in the chains to form pleated sheets
• The Two types of Beta sheet are Beta parallel sheets which are the same direction , while beta anta-parallel sheets are opposite direction
• Pleated Beta Sheets consist of 15 amino acid residues

Hydrogen Bonds

• Intramolecular hydrogen bonds are founded in helical structures
• Beta Sheets hydrogen bonds found within in globular, and extra in fibrous

Protein Turns

• Alpha helix and Beta sheets are linear so polypeptide must fold and create turns
• Protein turns use Glycine due to its small nature, Proline for the structure as the building blocks
• Four Amino acids are within four residues
• Structure is maintained by hydrogen bonds
• Two peptide bonds occur

Protein Stability

• Super-Secondary Protein Structures: use motifs that help in structural stability
• Alpha-Alpha motifs: use turns composed of Alpha units
• Beta-Beta structures use beta units
• Mixed Structures use a mix of parallel structures linked

Tertiary Proteins

• Proteins defined as complex and irregular self-folding in globular configuration
• The Single backbone structure has multiple secondary protein structures
• Protein molecules are folded in a compact way with external hydrophilic acids and forming an internal hydrophobic zone

Protein Structure and Functions

• Tertiary structure is stabilized by the formation of bonds between the lateral chains of the amino acids residues which became closer due to the folding
• Disulfide bonds with two cysteine residues formed during the folding
• Covalent and Noncovalent bonds are used during the formation of bonds to stabilize the compound
• Hydrophobic and Hydrogen bonds are used to bind with the folding

Protein Properties

• Soluble globular proteins become sequested when bonded with hydrophobic side chains with the removal of polar molecule like the Tyrosine and Leucine
• Hydrogen molecule bonding is created when between paired electrons
• Salt Bridges create positively charged acids binding with side chain
• Van der Waals interactions and polar interactions

Protein Uniqueness

• Tertiary structure provides native structures and determines its shape
• Fibrous proteins do not have tertiary structures
• Enzymes and primary determine the structure
• Chaperons bind and prevent the addition of other compounds

Quaternary Structure of Proteins

• Formed as subunits organized as monomers
• Supra-molecular organizations
• Identified as dimeic, trimeric and tetrameric
• Homopolymers if subunits are identical and Hetero for different
• Can be Stabilized by Hydrogen and Ionic binding

Protein Stability

• Structure stabilized with Hydrogen and Ionic bonds
• Disruptive forces if not stabilized
• Serve as activation switch
• Protein configuration due to reaction with the binding properties of the sub units

Structures of proteins

• Fibrous made of single chain molecules for the single helix, linked by sheets
• Bond held by single helix

Protein Keratin

• Hard Keratin protects mammals with cells
• Soft keratin Cytoskeletal supports epithelia

Hair formation:

• 2 alpha Keratin Molecules with Helix Structure
• superhelixes twist to form microfibrils
• microfibrils form macrofibrils stabilized by molecules
• Macrofibrils form a fiber which is One single strand of hair

Protein Properties

• Based on structure it allows for extensibility of stretch and retract molecules.
• Insoluble in nature which is why non polar bind to polar compounds together

ECM properties

• Is the primary structure
• secreted by fibroblasts, chondroblasts
• Contains 1000 acids
• Formed using Repetition
• Formed when 3 Helicial molecules coil together stabilized with hydrogen Bonds
• Consist of collagen
• Resistance

Elastin

• Has properties with ECM
• Synthesized by fibroblasts
• Requires flexibility
• Reticulated due to bonds
• Collagen with little properties

Fiber Properties

• Created when larva forms for other insects by connecting anti-parallel beta sheets
• With amorphous bonds forms an inextensible solid
• Small with Glycine, Alanine for the 4/5 ratio
• Used for structure
• Alpha protein is helix
• Beta proteins are sheets

Protein Bonds

• 3D shows protein bond interactions
• Dynamic does bond fixed