Natural Polymers, Bonds, and Macromolecules

Types of Natural Polymers

• Cellulose is a homopolymer composed of identical glucose units
• Starch, another homopolymer, results from the interaction of many identical glucose molecules including amylose and amylopectin
• Protein is a heteropolymer formed by linking amino acids
• Nucleic acid is a heteropolymer created by combining different nucleotides like A, G, T, C, and U

Biological Functions of Macromolecules

• Polysaccharides function in structure and energy storage
• Nucleic acids store and transmit genetic information
• Proteins provide structure, functioning as enzymes, hormones, and receptors
• Lipids provide energy storage and form membranes

Types of Bonds

• Covalent bonds are strong (>0.5), with polar covalent bonds ranging from 0.5 to 1.7, and ionic bonds also present
• Non-covalent interactions include van der Waals forces, hydrogen bonding, electrostatic interactions, and hydrophobic interactions

Hydrophobic Effect

• Amphipathic molecules (both polar and non-polar groups) experience an entropy force which stabilizes non-polar regions of biomolecules known as the hydrophobic effect
• Dispersion of lipids in water causes surrounding water molecules to become highly ordered, decreasing entropy
• This process leads to the formation of clusters

Induced Dipoles

• Molecules without permanent dipole moments can become polar in an electric field, resulting in induced dipole interactions

Free Energy Rules

• Delta G < 0 indicates a reaction is thermodynamically favorable and exergonic (available to do work)
• G = 0 means the system is at equilibrium and the reaction is reversible
• G > 0 signifies a thermodynamically unfavorable, endergonic reaction

Functions of Carbohydrates

• Carbohydrates generate and store biological energy
• They are involved in molecular recognition, facilitating immune system binding to viruses or bacteria via glycoproteins
• They contribute to cellular protection (e.g., in bacteria and cell walls)
• They participate in cell signaling and adhesion
• They serve as biological lubricants and in controlling protein trafficking
• They maintain biological structure as seen in cellulose

Types of Carbohydrates

• Carbohydrates include monosaccharides (simple sugars), oligosaccharides (2-10 units), and polysaccharides (thousands of covalently linked monosaccharides)
• Polysaccharides can be homopolysaccharides (one type of monosaccharide) or heteropolysaccharides (more than one type)
• Aldoses have a highly oxidized aldehyde group, while ketoses possess a highly oxidized ketone functional group

Glucose

• Alpha glucose has the OH group on C6 facing down, while beta glucose has it facing up
• D/L configuration is determined by the position of the furthest hydroxyl group on the chiral carbon (right or left)
• Glucose can exist in chair (stable) or boat conformations

Chiral vs Achiral Molecules

• A rotated chiral molecule cannot be superimposed on its mirror image, unlike an achiral molecule
• Mirror images that are non-superimposable are enantiomers, while non-mirror images are diastereoisomers
• Molecules with n chiral centers have 2^n possible stereoisomers

Tautomers

• Tautomers are structural isomers of chemical compounds that readily interconvert
• Trioses convert between an aldose and a ketose through an enediol intermediate which is unstable and cannot be isolated

Monosaccharides

• Hexoses are the most common monosaccharides in nature, with D-glucose being the most abundant

Epimers

• Epimers are two sugars that differ in configuration around only one carbon atom

Monosaccharides in Solution

• Aldehydes or ketones react with an alcohol to form a hemiacetal or hemiketal, creating a new chiral center
• Further reaction with another alcohol forms an acetal or ketal
• Alpha and beta isomers are anomers, with the C1 carbon called the anomeric carbon atom
• Mutarotation is the interconversion between alpha and beta forms

Oxidation and Reduction Reactions

• Mutarotases are enzymes that catalyze mutarotation
• Aldehyde oxidation yields a carboxylic acid
• Aldehyde reduction yields an alcohol
• Monosaccharides are reducing agents; they can oxidize ferric and cupric ions

Nonreducing Sugars

• The anomeric carbon is involved in a glycosidic bond and cannot take the linear form from the cyclic form

Disaccharides

• Disaccharides consist of two monosaccharides covalently joined by an O-glycosidic bond
• N-glycosidic bonds are formed between an anomeric carbon and an amine group

Common Disaccharides

• Lactose is composed of galactose and glucose and is a reducing sugar
• Sucrose consists of glucose and fructose and is not a reducing sugar due to the absence of free anomeric carbon atoms
• Trehalose is made of two glucose molecules and is also a non-reducing sugar

Amylose vs Cellulose

• amylose has 1-4 linkages between alpha glucose molecules(bent ), whereas cellulose has these linkages between beta glucose molecules (fully extended)

Chitin

• Chitin is a linear homopolysaccharide of N-acetylglucosamine residues with 1-4 linkages
• Removal of the acetyl group forms chitosan, accelerating blood coagulation by attracting negatively charged platelets to form a loose clot

Bacterial Cell Wall

• Bacterial cell walls are made of peptidoglycan
• Gram-positive bacteria have thick cell walls with multiple layers of peptidoglycan
• Gram-negative bacteria possess a thinner cell wall with a single layer of peptidoglycan between inner and outer lipid bilayer membranes
• Lysozyme, an enzyme, kills bacteria by hydrolyzing the beta 1-4 glycosidic bond in the cell wall formed between chitin and N-acetylmuramic acid with 1-4 linkage

Glycosaminoglycans

• Glycosaminoglycans are components of proteoglycans
• They contain one amino sugar and another negatively charged sulfate or carboxylate group

Glycoconjugates

• Glycoconjugates are oligosaccharides covalently linked to lipids or proteins
• Saccharides attached to cell surfaces facilitate cell-to-cell recognition
• They include proteoglycans, glycoproteins, and glycolipids

Proteoglycans

• Proteoglycans include a trisaccharide linker to glycosaminoglycan connected to a serine residue in the core protein
• The xylose residue at the reducing end is joined to the anomeric carbon to the hydroxyl of the serine residue

Glycoproteins

• Glycoproteins are carbohydrate-protein conjugates formed via either O-glycosidic or N-glycosidic bonds

Glycolipids

• Glycolipids are membrane lipids with hydrophilic oligosaccharide heads that act as specific recognition sites for carbohydrate-binding proteins

Vitamins

• Four types of human red blood cells have different oligosaccharides in their membranes
• Vitamins partners for enzymes involved in metabolism, cell production, tissue repair, and vital processes
• The body can synthesize vitamins D, K, and B (niacin)
• Water-soluble vitamins are B and C, while fat-soluble vitamins are A, D, E, and K
• Vitamin C functions as its own coenzyme

Cofactors

• Cofactors are complex structures that cannot be synthesized by mammals
• They bind to proteins and are required for the protein's biological activity

Vitamin-Derived Coenzymes

• Act as electron carriers - ascorbic acid, niacin B3, riboflavin B2
• Ascorbate: the active form, antioxidant, iron absorption, coenzyme in hydroxylation reactions (collagen synthesis), dopamine, bile acid synthesis for tyrosine degradation
• Niacin: precursor for NAD and NADP, NAD+/NADH glycolysis and oxidative phosphorylation; NADP+/NADPH in redox balance and biosynthesis of fatty acids and nucleic acids (NAD = catabolic reactions vs NADP = anabolic reactions), reduction of NAD+/NADP+ converts benzenoid ring into quinonoid form (no charge on nitrogen), NADH absorbs light at 340 nm
• Riboflavin that is synthesized by bacteria, protists, fungi, plants and some animals is involved in redox reactions in the TCA cycle, respiratory chain in mitochondria, oxidation and metabolism of fatty acids and is a precursor for coenzymes FMN and FAD
• Vitamin B6 has coenzymes that catalyze a variety of reactions involving transamination, decarboxylation and racemization and its enzyme-coenzyme Schiff base is called internal aldimine
• Vitamin B12 has Corrine ring and is used in isomerization reactions and acts as a methyl group carrier
• Vitamin H, biotin (water soluble): Catalyzes carboxyl group transfer reactions and ATP-dependent carboxylation reactions
• Vitamin B9 contains pterin, PABA, and glutamate residue and coenzyme forms known as tetrahydrofolate
• Vitamin B1 contains pyrimidine ring and positively charged thiazolium ring and its coenzyme form is TPP -> ATP dependent phosphorylation
• Vitamin B5 is a precursor for coenzyme A and ACP domain in fatty acid synthase
• Vitamin A that has three active forms being retinol, retinal, retinoic acid is synthesized from beta-carotene, oxidation of retinol to form retinal (reversible) and retinoic (not reversible) and is involved in vision, protein synthesis and cell differentiation, supporting reproduction and growth
• Vitamin D and its D3 form is nonenzymatically formed in the skin from cholesterol, converted to 1,25-dihydroxycholecaciferol regulates calcium uptake in the intestine and calcium levels in the bones; and D2 is formed by UV irradiation of the ergosterol of yeast

Vitamin E and K

• Vitamin E: Phenol group can undergo oxidation to form a free radical, reducing agent
• Vitamin K: Involved in blood coagulation and serves as an enzyme cofactor in the synthesis of y-carboxyglutamic acid, important for the function of a number of proteins (clotting factors), reduced form acts as a coenzyme for carboxylase that produces modified glutamate side chain with these reactions are catalyzed by vitamin K and VKOR

Pka

• If the pH > pka = compound is deprotonated
• PH < pka = compound is protonated

Post-translational Modifications

• Results in a multitude of functions in the cell from signal transduction to gene regulation to modification of structure and dynamics

Disulfide Bonds

• Reversible formation of a disulfide bond by the oxidation of two molecules of cysteine = stabilizes the structures of many proteins

Spectroscopic Properties of Amino Acids

• Aromatic amino acids absorb UV light due to delocalized pi-electrons

Peptide Bond

• Cis configuration has steric hindrance, therefore trans is strongly favored,

Types of Protein Structure

• The primary protein structure is its amino acid sequence
• The Secondary protein structure proposed by Linus Pauling included alpha helix and beta sheet, tight turns (beta turns/beta bends, type I and II, I is more common), and beta buldges, beta sheets can be antiparallel or parallel
• The protein Tertiary structure is its folding
• The Quaternary protein structure has multiple polypeptide chains involved

Fibrous Proteins

• Filamentous, elongated -> quaternary interactions, structural roles
• a-keratin, collagen, fibroin/b-sheet protein

Globular proteins

• Made up of two or more domains = single continuous portion of the polypeptide or an entire chain

Unfolding of Protein Structure

• Urea treatment resulted in unfolding of protein and b-mercaptoethanol reduced disulfide bonds

Folding Requirements

• Stability -> delta G < 0
• S = all the microstates/configurations associated with the protein and the solvent, protein conformational entropy <0, solvent entropy >0, protein enthalpy <0
• H = internal energy components of protein and solvent

Denaturation

• External stresses disrupt the forces found in proteins = loss of structure and function
• Heat, high concentrations of denaturants like urea or guanidinium chloride

Amyloid Fibrils in Alzheimer's

• The amyloid b peptides misfolding results inn amyloid fibrils to lose structure and function -> these become nucleation sites for polymerization

Myoglobin vs Hemoglobin

• Myoglobin a vs Hemoglobin has a single subunit vs 4 subunits being 2 alpha + 2 beta
• Myoglobin has very high affinity for oxygen at all partial pressures = ideal for storage, high affinity at lower partial pressures vs Hemoglobin binds in lungs and releases it in tissues -> allosteric effect, from tense state low affinity to relaxed state = high affinity

Oxygen Binding in Globin

• Iron forms covalent bonds with 6 ligands -> 4 porphyrin N groups, proximal ligand and sixth location for binding oxygen
• Whereas CO binds to free heme in a linear configuration, oxygen binds in a bent configuration -> stabilized by additional H bond with distal histidine

Bohr Effect

• Hemoglobin-O2 binding is pH dependent, higher CO2 = lower pH because of carbonic anhydrase to carbonic acid, shifts the curve to the left -> tense state

Analyzing Protein Structure

• X-ray crystallography uses diffraction pattern translated to yield a 3d distribution of electron density, fourier transformation -> used to build atomic structure of the protein or nucleic acid
• NMR reveals solution ensemble structures and dynamics
• Cryo electron microscopy reveals the 3D structures in near atomic detail to study its folding and function

Enzyme Specificity

• Absolute specificity means the enzyme only catalyzes one reaction
• Group specificity means the enzyme acts only on molecules with specific functional groups
• Linkage specificity: the enzyme acts on particular type of chemical bond
• Stereochemical specificity: the enzyme acts on particular steric or optical isomer

Metal Ions as Cofactors

• Metals that participate as catalysts in ionic interactions between an enzyme bound metal and a substrate can help orient the substrate for reaction or stabilize charged reaction transition states, and form coordination compounds
• Eg: Enolase, catalase/peroxidase hemoproteins + iron, ascorbic acid oxidase + copper, carbonic and alcohol dehydro

Enzyme Inhibitors

• Reversible, irreversible, suicide (undergoes first few steps but is converted to a very reactive compound that combines irreversibly with the enzyme), allosteric inhibitors

Competitive Inhibition vs Non-competitive Inhibition vs Uncompetitive Inhibition

• No effect on Vmax, increased Km vs Vmax is reduced, Km is constant
• Bind only to ES complex, at a site distinct from the active site, Vmax decreases, Km decreases

Oxidoreductases

• Catalyze a reaction in which NAD or NADP accepts a hydride ion from a reduced substrate, or NAPDH or NADH donates a hydride ion to an oxidized substance

Transferases

• Catalyze a transfer of a group from one molecule to another; for example, kinases transfer of terminal phosphoryl group from ATP to acceptor nucleophile
• Aminotransferase a-animo group transferred to a-carbon atom

Hydrolases

• Catalyze enzymatic depolymerization of proteins, carbohydrates and nucleic acids in hydrolysis reactions, cleavage of C-O, C-N, C-C and P-N bonds

Ligases

• Covalently link two molecules together like DNA ligase that links Okazaki fragments together
• Ubiquitin ligase: attachment of ubiquitin to its substrate proteins

Lyases

• They catalyze addition an elimination reactions, eg in the TCA cycle

Isomerases

• Catalyse changes within one molecule, converting a molecule from one isomer to another

Lipid Functions

• Lipids store and provide energy, provide insulation, and help manufacture steroids and bile salts
• Lipids play a role in transporting fat-soluble nutrients in the blood, signal, and manufacture major sex hormones
• Lipids are a key structure to all cell membranes

Types of Rancidity

• Oxidative rancidity reacts with oxygen free radicals with PUFA, forms peroxides and epoxides, end products are aldehyde, ketones and other volatile products
• Hydrolytic rancidity is due to contamination of fat by lipase leading to formation of diacyl and monoacylglycerols with free fatty acids, end product of epoxide and peroxide
• Microbial rancidity: bacteria, molds and yeast breakdown chemical structures in oil producing unwanted odours and flavours and water is needed for their microbial growth

Wax

• Is formed from fatty acid + long chain alcohol
• Used in cosmetic, candles, pharmaceutics industry, polishing lubricant