1.1 Overview of metabolism

Metabolism is the engine of life, powering everything from growth to waste removal. It's a complex network of chemical reactions that keep organisms alive and thriving. Understanding metabolism is key to grasping how our bodies function and maintain balance.

This section breaks down the basics of metabolism, exploring its organization and regulation. We'll look at how anabolic and catabolic processes work together, and how enzymes play a crucial role in making it all happen.

Metabolism: Life's Essential Processes

Fundamental Concepts of Metabolism

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• Metabolism encompasses all chemical reactions within living organisms maintaining life functions (energy production, biosynthesis, waste removal)
• Metabolic processes enable growth, reproduction, cellular structure maintenance, and environmental response
• Metabolism integrates interconnected and tightly regulated biochemical pathways
• Categorization divides metabolism into primary (essential for survival) and secondary (specific to certain organisms or conditions) types
• Metabolic rate varies based on factors (body size, age, gender, environmental conditions)

Metabolic Pathways and Cellular Functions

• Metabolic reactions form integrated networks supporting diverse cellular functions
• Energy production pathways generate ATP through processes (glycolysis, citric acid cycle, oxidative phosphorylation)
• Biosynthetic pathways construct complex molecules (proteins, lipids, nucleic acids) from simpler precursors
• Catabolic pathways break down nutrients (carbohydrates, proteins, lipids) to release energy and produce building blocks
• Waste removal pathways eliminate toxic byproducts and maintain cellular homeostasis

Regulation and Adaptation of Metabolism

• Metabolic flexibility allows organisms to adapt to changing environmental conditions
• Hormonal signaling coordinates metabolic processes across different tissues and organs
• Circadian rhythms influence metabolic activity patterns throughout the day
• Metabolic disorders arise from disruptions in normal metabolic processes (diabetes, metabolic syndrome)
• Understanding metabolism informs medical treatments and lifestyle interventions for health optimization

Anabolism vs Catabolism

Anabolic Processes: Building Complexity

• Anabolism constructs complex molecules from simpler precursors, requiring energy input
• Anabolic reactions typically endergonic, consuming energy to create larger, more complex structures
• Protein synthesis builds polypeptides from amino acids, essential for cellular structure and function
• Lipid synthesis produces fatty acids and complex lipids (phospholipids, triglycerides) for energy storage and membrane components
• Gluconeogenesis generates glucose from non-carbohydrate precursors, maintaining blood glucose levels during fasting

Catabolic Processes: Breaking Down for Energy

• Catabolism breaks down complex molecules into simpler ones, often releasing energy
• Catabolic reactions typically exergonic, releasing energy for cellular use
• Glycolysis breaks down glucose into pyruvate, producing ATP and NADH
• Fatty acid oxidation degrades fatty acids into acetyl-CoA, generating NADH and FADH2 for ATP production
• Protein degradation breaks down proteins into amino acids, used for energy or biosynthesis

Balancing Anabolism and Catabolism

• Anabolism and catabolism balance maintains cellular homeostasis and overall organismal health
• Energy storage during excess nutrient availability involves anabolic processes (glycogen synthesis, lipogenesis)
• Energy mobilization during nutrient scarcity relies on catabolic processes (glycogenolysis, lipolysis)
• Hormones (insulin, glucagon) regulate the balance between anabolic and catabolic states
• Metabolic disorders often result from imbalances between anabolic and catabolic processes (obesity, cachexia)

Organization of Metabolic Pathways

Structural Organization of Pathways

• Metabolic pathways consist of sequential enzymatic reactions converting substrates into specific products
• Pathway organization includes linear sequences, branched networks, and cycles for efficient energy transfer and product formation
• Compartmentalization within cellular organelles (mitochondria, endoplasmic reticulum) enhances pathway efficiency and regulation
• Metabolic networks integrate multiple pathways through shared intermediates and regulatory molecules (ATP, NADH, acetyl-CoA)
• Pathway directionality determined by thermodynamics and regulation, with some pathways reversible under certain conditions

Regulatory Mechanisms of Metabolic Pathways

• Allosteric regulation modulates enzyme activity through effector molecule binding to allosteric sites
• Covalent modification alters enzyme activity through chemical changes (phosphorylation, acetylation)
• Transcriptional and translational control regulates enzyme production in response to cellular needs
• Hormonal regulation coordinates pathway activity across different tissues and organs
• Feedback inhibition prevents overproduction of pathway end products
• Feed-forward activation enhances pathway flux in response to increased substrate availability

Integration and Coordination of Pathways

• Key intermediates (pyruvate, acetyl-CoA) serve as metabolic hubs connecting multiple pathways
• Energy carriers (ATP, NADH) link catabolic and anabolic processes
• Regulatory molecules (AMP, citrate) coordinate activity across different pathways
• Metabolic cycles (citric acid cycle, urea cycle) efficiently process intermediates and conserve energy
• Interorgan metabolism coordinates nutrient utilization and energy distribution throughout the body

Enzymes in Metabolic Reactions

Enzymatic Catalysis and Reaction Kinetics

• Enzymes dramatically increase metabolic reaction rates without being consumed
• Catalytic activity enables reactions at physiologically relevant rates and temperatures
• Enzyme specificity ensures precise control over metabolic pathways
• Active sites provide unique microenvironments facilitating substrate to product conversion
• Enzyme kinetics described by parameters (Km, Vmax) provide insights into efficiency and regulation
• Michaelis-Menten equation models enzyme kinetics: $v = \frac{V_{max}[S]}{K_m + [S]}$
• Lineweaver-Burk plot linearizes enzyme kinetics data for easier analysis

Cofactors and Coenzymes in Enzyme Function

• Cofactors work with enzymes to facilitate specific chemical transformations
• Inorganic cofactors include metal ions (Zn2+, Mg2+, Fe2+)
• Organic cofactors (coenzymes) derived from vitamins (NAD+, FAD, coenzyme A)
• Coenzymes often act as electron carriers or functional group donors in metabolic reactions
• Some enzymes require multiple cofactors for optimal activity (cytochrome c oxidase)

Enzyme Regulation in Metabolic Control

• Allosteric regulation modulates enzyme activity through conformational changes
• Covalent modification alters enzyme activity (phosphorylation in glycogen metabolism)
• Zymogen activation controls potentially harmful enzymes (trypsinogen to trypsin)
• Compartmentalization restricts enzyme access to substrates (lysosomal enzymes)
• Isozymes provide tissue-specific metabolic control (lactate dehydrogenase isoforms)
• Enzyme inhibitors modulate metabolic flux (statins inhibiting HMG-CoA reductase)