Exam 2 Med Chem PDF

ENZYMES 1. What are Enzymes, and What Properties Do They Display? Definition: Enzymes are proteins that act as catalysts, speeding up biochemical reactions without being consumed in the process. Properties: They display high specificity (they act on specific substrates), are highly...

ENZYMES 1. What are Enzymes, and What Properties Do They Display? Definition: Enzymes are proteins that act as catalysts, speeding up biochemical reactions without being consumed in the process. Properties: They display high specificity (they act on specific substrates), are highly efficient, work under mild conditions (e.g., body temperature and pH), and are regulated by various cellular factors. Usefulness: Enzymes are essential in processes like digestion, DNA replication, and cellular metabolism. 2. Biomolecules That Can Act as Enzymes and Their Prosthetic Groups Protein Enzymes: Most enzymes are proteins, but some RNA molecules (ribozymes) also act as enzymes. Prosthetic Groups: These are non-protein components that are tightly bound to enzymes and essential for their function, like heme in hemoglobin or FAD in flavoproteins. 3. Enzyme Classification and Nomenclature Classes: Enzymes are classified based on the type of reaction they catalyze. The main classes include oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. Nomenclature: Enzyme names often end in “-ase” and describe the type of reaction (e.g., lactase for lactose breakdown). 4. Substrate Selectivity and Enzyme Kinetics Selectivity: Enzymes are highly specific, often binding only to one specific substrate or a small group of similar substrates. Enzyme Kinetics: This studies the rate at which enzymes catalyze reactions. Enzymes accelerate reactions by lowering the activation energy (ΔG‡\Delta G^{\ddagger}ΔG‡), which they achieve through binding energy and catalytic mechanisms. 5. Impact on Activation Energy (ΔG‡\Delta G^{\ddagger}ΔG‡) and Binding Energy Binding Energy: Enzymes use binding energy from the enzyme-substrate interaction to stabilize the transition state, reducing the activation energy required and speeding up the reaction. 6. Main Catalytic Mechanisms of Enzymes Mechanisms include: ○ Acid-Base Catalysis: Enzymes donate or accept protons. ○ Covalent Catalysis: Enzymes form temporary covalent bonds with substrates. ○ Metal Ion Catalysis: Metal ions stabilize charged intermediates or participate in redox reactions. 7. Importance of Studying Enzyme Kinetics Kinetics helps us understand enzyme efficiency, regulation, and role in disease, drug action, and metabolism. 8. Michaelis-Menten Equation and Kinetic Parameters (kcat, Km, kcat/Km) Michaelis-Menten Equation: Describes how the reaction rate (v) depends on substrate concentration ([S]). kcat (Turnover Number): Maximum number of substrate molecules converted to product per enzyme per second. Km (Michaelis Constant): Substrate concentration at which the reaction rate is half of VmaxV_{\text{max}}Vmax​. kcat/Km (Catalytic Efficiency): Reflects enzyme efficiency; higher values indicate a more efficient enzyme. 9. Kinetics at Low vs. High Substrate Concentrations At low [S]: Reaction rate increases almost linearly with [S]. At high [S]: Enzymes become saturated, and the rate reaches VmaxV_{\text{max}}Vmax​, meaning adding more substrate has minimal effect on the rate. 10. Enzyme Inhibitors and Types of Inhibition Inhibitors: Molecules that decrease enzyme activity. Types include: ○ Competitive: Compete with substrate for the active site. ○ Uncompetitive: Bind only to the enzyme-substrate complex. ○ Mixed: Bind to either the enzyme or enzyme-substrate complex, but affect it differently than uncompetitive inhibition. 11. Irreversible Inhibitors Bind permanently to the enzyme, often leading to permanent inactivation. Example: Penicillin irreversibly inhibits enzymes involved in bacterial cell wall synthesis. 12. Regulation of Enzyme Activity Regulatory Mechanisms: Include feedback inhibition, covalent modification (like phosphorylation), and control by activators or inhibitors. 13. Allosteric Regulators and Their Effect on Enzymes Allosteric regulators bind to sites other than the active site, altering enzyme activity. They can activate or inhibit the enzyme. 14. Examples of Reversible and Irreversible Covalent Modification Reversible: Phosphorylation, acetylation. Irreversible: Proteolytic cleavage (e.g., activation of digestive enzymes like trypsin). Carbohydrates 1. What Are Carbohydrates and Their Roles in Living Organisms? ○ Definition: Carbohydrates are organic molecules made of carbon, hydrogen, and oxygen, typically following the formula (CH₂O)ₙ. ○ Roles: They serve as energy sources (e.g., glucose), provide structural support (e.g., cellulose in plants), and play roles in cell signaling and immune responses. 2. Carbohydrate Classification and Main Structural Features ○ Monosaccharides: Single sugar units like glucose and fructose, characterized by carbonyl groups (aldehyde or ketone) and hydroxyl groups. ○ Disaccharides: Two monosaccharides linked together (e.g., sucrose). ○ Polysaccharides: Long chains of monosaccharides, either branched or unbranched, like starch (energy storage in plants) and glycogen (energy storage in animals). 3. Isomers of Monosaccharides: Configuration and Conformation ○ Types: Structural Isomers: Same formula but different structure (e.g., glucose and fructose). Stereoisomers: Same structure but different spatial arrangement; includes D and L forms. Anomers: Isomers formed during cyclization, differing at the carbonyl carbon (α and β forms). ○ Interconversion: In solution, α and β anomers can interconvert in a process called mutarotation. 4. Cyclic Structure of Monosaccharides and Anomers  ○ Formation: Monosaccharides form rings when the carbonyl group reacts with a hydroxyl group. ○ Anomers: α and β forms differ at the anomeric carbon, which is the carbon involved in ring formation. 5. Sugar Derivatives from Hexoses ○ Examples: Hexoses can form sugar acids, sugar alcohols, and deoxy sugars. ○ Roles: These derivatives can be involved in cellular signaling, structure, and metabolic pathways. 6. Redox Properties of Monosaccharides ○ Monosaccharides can be oxidized or reduced. Their redox reactions form the basis for glucose monitoring systems in blood or urine tests. 7. Disaccharides and Polysaccharides: Structure and Function ○ Disaccharides: Formed by glycosidic bonds between two monosaccharides (e.g., lactose, sucrose). ○ Polysaccharides: Starch, glycogen, and cellulose each have unique structuresdc oo suited to storage (starch and glycogen) or structural roles (cellulose). 8. Glycoconjugates: Classes, Properties, and Physiological Roles ○ Glycoproteins and Glycolipids: Involved in cell-cell communication, immune response, and structural integrity of cells. Diseases 1. Diabetes: Affects carbohydrate metabolism due to insulin issues, leading to high blood glucose. 2. Heart Conditions: Carbohydrates can impact heart disease risk, especially through sugar-linked processes in blood clotting. 3. Infections: Bacterial and viral infections often interact with host glycoconjugates. 4. Ulcers and Cancer: Carbohydrate modifications are involved in gastrointestinal diseases and cancer cell recognition. Drugs 1. Penicillins and Combos with β-lactamase Inhibitors: Antibiotics targeting bacterial cell walls. 2. Digoxin: Used in heart failure, impacting carbohydrate-linked processes in heart muscle cells. 3. Eptifibatide: An antiplatelet drug used to prevent blood clots. 4. Heparin: An anticoagulant that interacts with carbohydrate structures to prevent clotting. Diagnostics 1. Glucose Monitoring: Includes Clinitab tablets and various strips (e.g., Dextrostix) for self-monitoring blood and urine glucose. Genetics and Biotechnology Concepts 1. Gene, Genome, Chromosome, and Information Flow ○ Gene: A DNA segment that codes for proteins or functional RNA. ○ Genome: The entire DNA sequence of an organism. ○ Chromosome: DNA-protein complexes that organize genes. ○ Information Flow: Follows DNA ➔ RNA ➔ Protein (central dogma). 2. DNA Cloning ○ Definition: Process of making identical copies of DNA. ○ Requirements: Restriction enzymes, vectors (e.g., plasmids), and host cells. ○ Biotechnological Implications: Enables production of pharmaceuticals, genetically modified organisms, and gene research. 3. Recombinant DNA Technology ○ Elements: Restriction enzymes, vectors, ligase, and host cells. ○ Steps: Cutting DNA, inserting it into vectors, transforming host cells, and selecting clones. ○ Process: Combines DNA from different sources to create new genetic combinations. 4. Restriction Endonucleases ○ Function: Cut DNA at specific sequences. ○ Outcome: Produce fragments with “sticky” or “blunt” ends, which can be joined with other DNA. 5. RFLP (Restriction Fragment Length Polymorphism) ○ Usage: Genetic mapping, forensic analysis, and disease detection. ○ Significance: Detects DNA sequence variations among individuals. 6. DNA Library ○ Definition: A collection of DNA fragments stored in vectors. ○ Types: Genomic (all DNA) and cDNA libraries (expressed genes). ○ Generation: Involves fragmenting DNA and inserting fragments into vectors. 7. PCR (Polymerase Chain Reaction) ○ Purpose: Amplifies specific DNA sequences. ○ Steps: Denaturation, annealing, extension. ○ Materials: DNA template, primers, nucleotides, DNA polymerase. 8. Therapeutic Entities from Recombinant DNA ○ Examples: Insulin, growth hormones, monoclonal antibodies. ○ Application: Used in treating diseases like diabetes and cancers. 9. “Omics” Fields ○ Examples: Genomics (genes), proteomics (proteins), transcriptomics (RNA), and metabolomics (metabolic pathways). Diseases and Drugs 1. Disease ○ Diabetes: Related to insulin production and regulation.  2. Drugs ○ Recombinant Insulin (e.g., Humulin): Produced through recombinant DNA to treat diabetes. Lipids 1. What Are Lipids, Their Classification, Characteristics, and Roles? ○ Definition: Lipids are hydrophobic molecules that include fats, oils, waxes, and certain vitamins. They are primarily made up of long hydrocarbon chains or rings. ○ Classification: Main classes are fatty acids, triglycerides, phospholipids, sphingolipids, and sterols. ○ Roles: Lipids are vital for energy storage, structural support in cell membranes, and as signaling molecules. 2. Fatty Acids: Nomenclature, Self-Assembly, Sources, and Essential Fatty Acids ○ Nomenclature: Based on the number of carbons and double bonds (e.g., 18:2 for linoleic acid). ○ Self-Assembly: They can form micelles or lipid bilayers due to their amphipathic nature (having both hydrophilic and hydrophobic parts). ○ Essential Fatty Acids: Includes linoleic acid and alpha-linolenic acid, which must be obtained through diet. Physiologically relevant ones include omega-3 and omega-6 fatty acids, important for cellular health. 3. Triglycerides and Waxes: Structure, Role, and Reactions ○ Structure: Triglycerides consist of three fatty acids attached to a glycerol backbone; waxes are long-chain fatty acids esterified with long-chain alcohols. ○ Role: They store energy, provide insulation, and serve as water repellents. ○ Reactions: Triglycerides undergo hydrolysis to release fatty acids for energy. 4. Glycerophospholipids: Structure and Function ○ Structure: Made of two fatty acids, glycerol, a phosphate group, and an additional functional group. ○ Role: They form the cell membrane's bilayer, which regulates what enters and exits cells. 5. Sphingolipids: Structure and Function ○ Structure: Built on a sphingosine backbone with one fatty acid and various head groups. ○ Role: Involved in cell membrane stability and signaling, particularly in nerve cells. 6. Phospholipase Specificity ○ Phospholipases: Enzymes that cleave specific bonds in phospholipids. Their specificity refers to the exact bond they target, which impacts cellular signaling and lipid turnover. 7. Physiological Impact of Glycosphingolipids ○ Role: Important in cell recognition and signaling, especially in the nervous system and immune response. 8. Sterols: Structure and Function ○ Structure: Sterols, like cholesterol, have a ring structure with a hydroxyl group.  ○ Role: Cholesterol stabilizes cell membranes and is a precursor for steroid hormones and vitamin D. 9. Role of Lipids/Sterols in Signaling, Hormones, and Vitamins ○ Signaling: Lipids and their derivatives (e.g., eicosanoids) act in signaling cascades, affecting inflammation and immune response. ○ Hormones: Steroid hormones, like cortisol, are derived from cholesterol. ○ Vitamins: Fat-soluble vitamins (A, D, E, K) are lipid-derived and have roles in vision, calcium regulation, antioxidant activity, and blood clotting. Diseases 1. Respiratory Distress Syndrome (RDS): Often linked to insufficient surfactant production in premature infants, affecting lung function. 2. Thrombosis and Inflammation: Lipids play a role in blood clotting and inflammatory responses. 3. Asthma: Lipid signaling molecules can influence bronchial inflammation. 4. Rickets: A deficiency in vitamin D leading to poor calcium metabolism and bone weakness. Drugs, Vitamins, and Supplements 1. Synthetic DPPC: Used as a lung surfactant replacement in RDS. 2. Linoleic and Linolenic Acids: Essential fatty acids for diet. 3. Prednisone/Prednisolone: Anti-inflammatory steroids derived from cholesterol. 4. Vitamins A, D, E, K: Important for vision (A), bone health (D), antioxidant function (E), and blood clotting (K1). 5. Coenzyme Q (CoQ10): Involved in cellular energy production. 6. Warfarin: Anticoagulant that acts by inhibiting vitamin K-dependent clotting factors. Nucleotides and Nucleic Acids 1. Structure of Nucleotides and Their Roles in Vivo ○ Nucleotide Structure: Composed of a nitrogenous base, a pentose sugar, and one or more phosphate groups. ○ Roles: They form the building blocks of DNA and RNA and are involved in cellular energy transfer (e.g., ATP), signaling (e.g., cAMP), and enzyme co-factors (e.g., NAD+). 2. Nucleoside vs. Nucleotide and Nitrogenous Bases ○ Nucleoside: Consists of a nitrogenous base attached to a sugar. ○ Nucleotide: A nucleoside with one or more phosphate groups. ○ Nitrogenous Bases: Purines (adenine, guanine) and pyrimidines (cytosine, thymine in DNA; uracil in RNA).  ○ Characteristics: Base pairing (A-T/U and G-C) allows for complementary DNA and RNA structures. 3. Nucleotides in DNA vs. RNA ○ DNA: Includes adenine (A), guanine (G), cytosine (C), and thymine (T). ○ RNA: Includes adenine (A), guanine (G), cytosine (C), and uracil (U). 4. Rare Nucleosides in DNA and RNA ○ Examples: Inosine in tRNA (RNA) is involved in wobble pairing, allowing flexibility in genetic code translation. 5. Phosphate Isomers of Nucleotides ○ Examples: ATP, ADP, AMP (adenosine triphosphate, diphosphate, monophosphate). ○ Roles: Involved in energy transfer and signaling. 6. DNA and RNA Structure and Differences ○ DNA: Double-stranded helix, with deoxyribose sugar; stable for long-term storage of genetic information. ○ RNA: Single-stranded, with ribose sugar; more reactive and primarily involved in protein synthesis and regulation. 7. A, B, and Z DNA Forms ○ A-DNA: Right-handed, compact form seen in low humidity. ○ B-DNA: Right-handed, most common, with a more extended helix. ○ Z-DNA: Left-handed, can form in high salt concentrations and may play roles in gene expression. 8. Unusual DNA Structures ○ Examples: G-quadruplexes, triple helices, formed under specific sequence or environmental conditions. 9. RNA Secondary Structures ○ Examples: Hairpins, loops, and bulges are formed due to base pairing within RNA molecules. 10. mRNA Structure Features: Contains a 5’ cap, coding region, and 3’ poly-A tail for stability and translation initiation. 11. DNA Denaturation and Sequence Information Definition: Separation of DNA strands by heat or chemical agents. Parameters: Melting temperature (Tm) indicates stability and GC content. 12. Non-Enzymatic Reactions of Nucleotides Examples: Deamination, depurination, and oxidation, often influenced by environmental factors. Physiological Impact: Can lead to mutations if not repaired. 13. UV-Induced DNA Damage Mechanism: Causes thymine dimers, leading to errors in replication and transcription. Disease Association: Xeroderma pigmentosum (sensitivity to UV due to DNA repair deficiency). 14. Other Functions of Nucleotides Beyond Nucleic Acids Examples: ATP (energy currency), cAMP (signaling), NAD+ (redox reactions). Diseases and Drugs 1. Diseases ○ Cancer: DNA damage and mutations are linked to cancer progression. ○ Xeroderma Pigmentosum: Genetic disorder affecting DNA repair, especially of UV damage. 2. Drugs ○ Anticancer Agents: Alkylators: Bind DNA covalently, causing crosslinks (e.g., mechlorethamine). Intercalators: Insert between DNA bases, disrupting replication (e.g., doxorubicin). Pyrimidine Analogs: Mimic nucleotides to disrupt synthesis (e.g., 5-fluorouracil). Purine Analogs: Mimic purines and inhibit DNA synthesis (e.g., 6-mercaptopurine). Bioenergetics Metabolism and Metabolic Pathways 1. Metabolism: The set of life-sustaining chemical reactions in organisms, divided into pathways that either build up (anabolism) or break down (catabolism) molecules. 2. Metabolic Pathways: Series of chemical reactions, where the product of one reaction serves as the substrate for the next. 3. Metabolites: Intermediate or end products of metabolism, such as glucose, pyruvate, or ATP. Main Metabolic Pathways 1. Catabolism: Breaks down molecules to release energy; examples include glycolysis and the citric acid cycle. 2. Anabolism: Synthesizes larger molecules from smaller ones, requiring energy input; examples include protein synthesis and nucleotide synthesis. Chemical Bonds and Reaction Classes 1. Bond Formation and Breakage: ○ Formation: Often involves condensation reactions. ○ Breakage: Commonly involves hydrolysis, breaking down molecules using water. 2. Classes of Reactions: ○ Condensation, Hydrolysis: Building and breaking molecules. ○ Redox Reactions: Transfer of electrons. ○ Isomerization: Rearrangement within molecules.  ○ Elimination and Group Transfer: Moving functional groups within or between molecules. 3. C-C Bond Reactions: ○ Carbonyl Addition: Adds carbons to a chain. ○ Decarboxylation: Removes a carbon as CO₂. 4. Isomerization and Elimination: ○ Isomerization: Changes a molecule’s shape without altering the molecular formula. ○ Elimination: Removes atoms or groups, creating double bonds or rings. 5. Group Transfer Reactions: ○ Common groups include phosphates, acyl, methyl. ○ Leaving Groups: Phosphate is common in energy transfers due to its stability. Bioenergetics and Thermodynamics 1. ΔG (Gibbs Free Energy): ○ Negative ΔG indicates a spontaneous reaction. ○ For sequential reactions, total ΔG determines spontaneity. ○ Related to Keq (equilibrium constant) and ΔE (energy change). 2. ATP and High-Energy Compounds: ○ ATP: Releases energy by hydrolyzing its high-energy phosphate bonds. ○ Energy Transfer: Phosphate group transfer, providing energy for cellular functions. Redox Reactions and Cofactors 1. Characteristics: Involve electron transfer and are crucial for energy production. 2. Redox Cofactors: ○ NAD⁺/NADH, FAD/FADH₂: Electron carriers in metabolic reactions. ○ Diseases: Deficiency in B vitamins can impair redox functions. Diseases and Related Drugs 1. Pellagra: Caused by a niacin (B3) deficiency, affecting redox reactions. 2. Ariboflavinosis: Caused by a riboflavin (B2) deficiency, disrupting energy production. 3. Drugs: Niacin and riboflavin supplements help treat or prevent these deficiencies.