🥼Organic Chemistry Unit 29 – Metabolic Pathways in Organic Chemistry

Key Concepts and Definitions

• Metabolism encompasses all chemical reactions involved in maintaining the living state of cells and organisms
• Anabolism constructs molecules from smaller units (requires energy input)
• Catabolism breaks down molecules into smaller units (releases energy)
• Metabolic pathways are series of enzymatic reactions that transform initial reactants into final products
• Enzymes are biological catalysts that speed up chemical reactions without being consumed in the process
• Cofactors are non-protein chemical compounds required for enzyme activity (e.g., metal ions, coenzymes)
• ATP (adenosine triphosphate) is the primary energy currency in cells, used to drive energy-requiring processes
  • Consists of adenosine, ribose sugar, and three phosphate groups
  • Hydrolysis of ATP to ADP (adenosine diphosphate) releases energy

Fundamental Metabolic Pathways

• Glycolysis breaks down glucose into pyruvate, generating ATP and NADH (occurs in cytoplasm)
• Citric acid cycle (Krebs cycle) oxidizes acetyl-CoA to produce NADH, FADH2, and ATP (occurs in mitochondrial matrix)
• Oxidative phosphorylation uses electron transport chain to create proton gradient, driving ATP synthesis (occurs in mitochondrial inner membrane)
• Pentose phosphate pathway generates NADPH and ribose-5-phosphate for biosynthetic reactions (occurs in cytoplasm)
• Fatty acid synthesis builds long-chain fatty acids from acetyl-CoA (occurs in cytoplasm)
  • Requires NADPH as a reducing agent
• Beta-oxidation breaks down fatty acids to generate acetyl-CoA (occurs in mitochondrial matrix)
• Amino acid metabolism involves synthesis and degradation of amino acids (occurs in various cellular compartments)

Enzymes and Their Roles

• Enzymes lower activation energy of reactions, increasing reaction rates
• Active site is the region where substrates bind and catalysis occurs
• Enzyme specificity ensures that only specific substrates are catalyzed
• Michaelis-Menten kinetics describes enzyme-substrate interactions and reaction rates
  • $V_0 = \frac{V_{max}[S]}{K_m + [S]}$, where $V_0$ is initial velocity, $V_{max}$ is maximum velocity, $[S]$ is substrate concentration, and $K_m$ is Michaelis constant
• Enzyme inhibition can be competitive (inhibitor binds active site) or non-competitive (inhibitor binds allosteric site)
• Allosteric regulation involves binding of effectors at sites other than the active site, modulating enzyme activity
• Enzymes can be regulated by post-translational modifications (e.g., phosphorylation)

Energy Flow and ATP Production

• ATP is generated through substrate-level phosphorylation and oxidative phosphorylation
• Substrate-level phosphorylation directly transfers phosphate group from high-energy compounds to ADP (e.g., in glycolysis)
• Oxidative phosphorylation couples electron transport chain to ATP synthase
  • Electron transport chain establishes proton gradient across inner mitochondrial membrane
  • ATP synthase uses proton gradient to drive ATP synthesis
• Chemiosmotic theory explains the mechanism of ATP production in oxidative phosphorylation
• ATP is utilized for various cellular processes (e.g., biosynthesis, active transport, muscle contraction)
• Energy balance is maintained by regulating ATP production and consumption

Regulation of Metabolic Pathways

• Metabolic pathways are regulated to maintain homeostasis and respond to cellular needs
• Allosteric regulation involves binding of effectors to enzymes, modulating their activity
  • Positive effectors enhance enzyme activity, while negative effectors inhibit it
• Feedback inhibition occurs when the end product of a pathway inhibits the first enzyme of the pathway
• Hormonal regulation controls metabolic pathways through signaling cascades (e.g., insulin stimulates glucose uptake and storage)
• Transcriptional regulation controls the expression of enzymes involved in metabolic pathways
• Compartmentalization of enzymes and substrates allows for spatial control of metabolic reactions
• Metabolic flux is the rate of flow of metabolites through a pathway, determined by enzyme activities and substrate concentrations

Interconnections Between Pathways

• Metabolic pathways are interconnected, allowing for the sharing of intermediates and regulation
• Glycolysis provides pyruvate for the citric acid cycle and fermentation pathways
• Citric acid cycle generates precursors for amino acid and nucleotide biosynthesis
• Pentose phosphate pathway produces NADPH for fatty acid synthesis and ribose-5-phosphate for nucleotide synthesis
• Amino acids can be converted to glucose (glucogenic) or acetyl-CoA (ketogenic)
• Acetyl-CoA is a central metabolite connecting carbohydrate, lipid, and amino acid metabolism
  • Produced by oxidation of glucose, fatty acids, and certain amino acids
  • Used for citric acid cycle, fatty acid synthesis, and ketone body production
• Anaplerotic reactions replenish citric acid cycle intermediates (e.g., conversion of pyruvate to oxaloacetate)

Practical Applications and Real-World Examples

• Understanding metabolic pathways is crucial for developing treatments for metabolic disorders (e.g., diabetes, obesity)
• Metabolic engineering involves modifying pathways to produce desired compounds (e.g., biofuels, pharmaceuticals)
  • Example: Engineered E. coli can produce insulin for the treatment of diabetes
• Metabolomics studies the complete set of metabolites in a cell or organism, providing insights into cellular processes
• Athletic performance can be enhanced by optimizing energy metabolism through diet and training
• Metabolic adaptation allows organisms to survive in diverse environments (e.g., hibernation, starvation)
• Metabolic profiling can be used for disease diagnosis and monitoring treatment response
  • Example: Elevated blood glucose levels are used to diagnose diabetes

Common Challenges and Study Tips

• Memorizing the details of each metabolic pathway can be challenging; focus on understanding the overall concepts and key enzymes
• Use visual aids (e.g., pathway diagrams, concept maps) to help organize and connect information
• Practice solving problems related to metabolic pathways to reinforce understanding
• Relate metabolic concepts to real-world examples to make the information more meaningful and memorable
• Study the regulation of metabolic pathways, as this is a common theme in exam questions
• Understand the interconnections between pathways and how they work together to maintain cellular homeostasis
• Review the key concepts and definitions regularly to ensure a strong foundation in metabolic pathways
• Seek help from instructors, tutors, or study groups when encountering difficulties in understanding the material