🧬Biochemistry Unit 11 – Introduction to Metabolism

What's Metabolism All About?

• Metabolism encompasses all chemical reactions involved in maintaining living cells and organisms
• Includes two main categories: catabolism (breaking down molecules) and anabolism (building up molecules)
• Catabolism releases energy by breaking down complex molecules into simpler ones
  • Includes processes like digestion and cellular respiration
• Anabolism consumes energy to construct complex molecules from simpler ones
  • Includes processes like protein synthesis and DNA replication
• Metabolic reactions are organized into metabolic pathways, series of linked enzymatic reactions
• Energy released from catabolic pathways (cellular respiration) is used to drive anabolic pathways (biosynthesis)
• Metabolism is tightly regulated to maintain homeostasis and respond to cellular needs

Key Players: Enzymes and Cofactors

• Enzymes are biological catalysts that speed up chemical reactions without being consumed
• Lower activation energy required for reactions to occur, making them more energetically favorable
• Highly specific, typically catalyzing a single reaction or a set of closely related reactions
• Active site is the region where the substrate binds and the reaction takes place
  • Substrate specificity is determined by the shape and chemical properties of the active site
• Cofactors are non-protein molecules required for enzyme function
  • Can be inorganic (metal ions like Fe2+, Mg2+) or organic (coenzymes like vitamins)
• Coenzymes are organic molecules that assist enzymes in catalyzing reactions
  • Examples include NAD+ (nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide)
• Enzyme activity can be regulated by various factors (pH, temperature, inhibitors, activators)

Energy Currency: ATP and Friends

• ATP (adenosine triphosphate) is the primary energy currency in living organisms
• Consists of adenosine (adenine base + ribose sugar) and three phosphate groups
• Energy is stored in the high-energy phosphate bonds between the phosphate groups
• Hydrolysis of ATP to ADP (adenosine diphosphate) + Pi (inorganic phosphate) releases energy for cellular processes
• ATP is regenerated from ADP + Pi through substrate-level phosphorylation or oxidative phosphorylation
• Other high-energy compounds also play important roles in energy transfer
  • GTP (guanosine triphosphate) is involved in protein synthesis and signal transduction
  • Phosphocreatine serves as an energy reservoir in muscle cells
• NADH and FADH2 are electron carriers that transfer electrons during cellular respiration

Catabolic Pathways: Breaking It Down

• Catabolic pathways break down complex molecules into simpler ones, releasing energy
• Cellular respiration is a major catabolic pathway that breaks down glucose to release energy
  • Occurs in three stages: glycolysis, Krebs cycle (citric acid cycle), and electron transport chain
• Glycolysis takes place in the cytoplasm and breaks down glucose into two pyruvate molecules
  • Produces a net gain of 2 ATP and 2 NADH molecules
• Pyruvate enters the mitochondria and is converted to acetyl-CoA, which enters the Krebs cycle
• Krebs cycle oxidizes acetyl-CoA, generating CO2, 3 NADH, 1 FADH2, and 1 GTP (or ATP) per cycle
• Electron transport chain (ETC) is the final stage of cellular respiration
  • NADH and FADH2 donate electrons to the ETC, creating a proton gradient across the inner mitochondrial membrane
  • Proton gradient drives ATP synthesis through oxidative phosphorylation via ATP synthase
• Other catabolic pathways include beta-oxidation of fatty acids and amino acid catabolism

Anabolic Pathways: Building It Up

• Anabolic pathways construct complex molecules from simpler ones, requiring an input of energy
• Photosynthesis is a major anabolic pathway in plants that converts light energy into chemical energy
  • Light-dependent reactions capture light energy and generate ATP and NADPH
  • Calvin cycle (light-independent reactions) uses ATP and NADPH to fix CO2 into glucose
• Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors (amino acids, lactate, glycerol)
  • Occurs primarily in the liver and is important for maintaining blood glucose levels during fasting
• Lipogenesis is the synthesis of fatty acids and triglycerides from excess carbohydrates
  • Occurs in the liver and adipose tissue, storing energy for later use
• Amino acid synthesis pathways produce essential and non-essential amino acids
  • Essential amino acids cannot be synthesized by the body and must be obtained from the diet
• Nucleotide synthesis pathways generate purine and pyrimidine nucleotides for DNA and RNA synthesis

Regulation: Keeping Things in Check

• Metabolic regulation ensures that cells maintain homeostasis and respond to changing energy needs
• Allosteric regulation involves the binding of effectors (activators or inhibitors) to enzymes at sites other than the active site
  • Effector binding causes conformational changes that alter enzyme activity
  • Example: ATP allosterically inhibits phosphofructokinase (PFK) in glycolysis to prevent excessive ATP production
• Feedback inhibition occurs when the end product of a pathway inhibits an earlier enzyme in the pathway
  • Helps prevent accumulation of excess products and maintains homeostasis
  • Example: Isoleucine inhibits threonine deaminase, the first enzyme in its own biosynthetic pathway
• Hormonal regulation allows for long-term control of metabolic pathways
  • Insulin promotes glucose uptake and storage (glycogenesis) while inhibiting glucose production (gluconeogenesis)
  • Glucagon stimulates glucose production (glycogenolysis and gluconeogenesis) during fasting
• Transcriptional regulation controls the expression of genes encoding metabolic enzymes
  • Transcription factors (activators or repressors) bind to specific DNA sequences to regulate gene expression
  • Example: SREBP (sterol regulatory element-binding protein) activates genes involved in lipid synthesis when cellular cholesterol levels are low

Connecting the Dots: Metabolic Integration

• Metabolic pathways are interconnected and work together to maintain cellular homeostasis
• Glucose-6-phosphate is a central metabolite that connects several pathways
  • Can enter glycolysis for energy production, pentose phosphate pathway for NADPH and ribose production, or glycogenesis for storage
• Acetyl-CoA is another key metabolite that links carbohydrate, lipid, and amino acid metabolism
  • Produced from pyruvate (carbohydrates), fatty acids (lipids), and certain amino acids
  • Can enter the Krebs cycle for energy production or be used for fatty acid and cholesterol synthesis
• Amino acids can be used for protein synthesis or catabolized for energy production
  • Glucogenic amino acids can be converted to glucose via gluconeogenesis
  • Ketogenic amino acids can be converted to ketone bodies or fatty acids
• Metabolic flexibility allows organisms to adapt to different fuel sources depending on availability
  • During fasting, the body shifts from glucose to fatty acids and ketone bodies for energy production
  • Exercise promotes the use of glucose and fatty acids for energy production in skeletal muscle

Real-World Applications

• Understanding metabolism is crucial for developing treatments for metabolic disorders
  • Type 2 diabetes is characterized by insulin resistance and impaired glucose metabolism
  • Obesity is associated with dysregulation of lipid metabolism and increased risk of metabolic diseases
• Metabolic engineering involves modifying metabolic pathways to produce desired compounds
  • Genetically engineered bacteria can produce insulin, biofuels, and other valuable products
  • Plants can be engineered to enhance nutrient content (golden rice with increased vitamin A) or resistance to environmental stresses
• Cancer metabolism is a key target for developing new therapies
  • Cancer cells exhibit altered metabolism, relying heavily on aerobic glycolysis (Warburg effect)
  • Targeting metabolic vulnerabilities in cancer cells can lead to new treatment strategies
• Personalized nutrition and precision medicine take into account individual metabolic differences
  • Genetic variations can influence enzyme activities and nutrient requirements
  • Tailoring diets and treatments based on metabolic profiles can optimize health outcomes
• Athletic performance can be enhanced by understanding exercise metabolism
  • Training adaptations improve the efficiency of energy production and utilization in skeletal muscle
  • Nutritional strategies (carbohydrate loading, ketone supplementation) can support optimal performance