MT

Video Notes: Metabolism and Characteristics of Life

Metabolism: Definition and Scope

  • Metabolism is the sum of all chemical reactions in living organisms that support life, including energy production, growth, maintenance, and reproduction.
  • It includes catabolic (degradative) and anabolic (synthetic) pathways that are interdependent.

Anabolism and Catabolism

  • Anabolism: synthesis of complex molecules from simpler ones; requires energy; examples: protein synthesis, glycogen synthesis, fatty acid synthesis.
  • Catabolism: breakdown of complex molecules to simpler ones, releasing energy; examples: glycolysis, beta-oxidation, proteolysis.
  • Importance: energy capture (ATP, NADH) from catabolic pathways powers anabolic biosynthesis and cellular processes.

Energy Currency and Thermodynamics

  • Primary energy carriers: ATP, ADP, AMP; reducing equivalents NADH, FADH2.
  • Energy coupling: Exergonic (−) reactions drive endergonic (+) reactions.
  • Free energy equation: \Delta G = \Delta H - T\,\Delta S
  • ATP hydrolysis energy: \Delta G_{ATP} \approx -50\,\text{kJ/mol} under cellular conditions (approx; standard value around -30.5 kJ/mol; actual value depends on concentrations).
  • Electron carriers deliver electrons to the ETC to create a proton gradient used by ATP synthase to generate ATP.

Major Pathways Overview

  • Glycolysis:
    • Location: cytosol.
    • Convert glucose to pyruvate; net yield of 2\,ATP and 2\,NADH per molecule of glucose.
    • Overall equation: \text{Glucose} + 2\,NAD^+ + 2\,ADP + 2\,Pi \rightarrow 2\,\text{pyruvate} + 2\,NADH + 2\,ATP + 2\,H2O + 2\,H^+
    • Phases: investment of 2 ATP in the first half; payoff in the second half.
  • Pyruvate oxidation (pyruvate dehydrogenase reaction):
    • Location: mitochondrial matrix.
    • Pyruvate → acetyl-CoA + CO₂ + NADH; per glucose: 2 NADH.
  • Citric acid cycle (Krebs cycle):
    • Location: mitochondrial matrix.
    • For each acetyl-CoA: 3 NADH, 1 FADH₂, 1 GTP (equivalently ATP).
    • Per glucose (two acetyl-CoA): 6\,NADH + 2\,FADH2 + 2\,GTP + 4\,CO2
  • Oxidative phosphorylation and electron transport chain (ETC):
    • NADH and FADH₂ donate electrons to the ETC, protons pumped across inner mitochondrial membrane creating a proton motive force.
    • ATP synthase uses proton gradient to generate ATP; typical yield: \approx 26-28\,\text{ATP} per glucose (varies with shuttle mechanisms and organism).
  • Overall ATP yield from complete glucose oxidation:
    • Common teaching range: \approx 30-32\,\text{ATP per glucose} in many eukaryotic cells.
    • Range can be 32-38 in some prokaryotes depending on ATP yields and shuttles.

Regulation and Control

  • Enzyme regulation:
    • Key control points: glycolysis (e.g., phosphofructokinase-1, hexokinase), pyruvate dehydrogenase complex, citrate synthase.
  • Hormonal regulation:
    • Insulin promotes anabolic pathways (glycolysis, lipogenesis, protein synthesis).
    • Glucagon, epinephrine promote catabolic pathways (glycogenolysis, gluconeogenesis, lipolysis).
  • Substrate and energy status:
    • High ATP/ADP ratio inhibits catabolic flux; low energy accelerates catabolism.
  • Allosteric regulation and covalent modification modulate enzyme activities.
  • Tissue-specific regulation:
    • Liver, muscle, adipose have distinct priorities (glucose homeostasis, energy storage, fatty acid oxidation).

Real-World Relevance and Applications

  • Energy balance and weight management:
    • Energy intake vs expenditure dictates storage (lipogenesis) or mobilization (lipolysis).
  • Exercise physiology:
    • Short bursts rely more on glycolysis and phosphocreatine; endurance activities rely more on aerobic respiration.
  • Nutrition:
    • Carbohydrate, fat, and protein intake shape substrate availability for metabolism.
  • Metabolic disorders:
    • Diabetes mellitus impairs glucose handling; mitochondrial diseases disrupt ATP production.
  • Medical and athletic optimization:
    • Understanding metabolic flux helps in designing diets and training programs.

Conceptual Connections and Philosophical Implications

  • Metabolism as an outcome of energy conservation and redox balance across cells.
  • Interplay of chemistry and biology: redox reactions, enzyme kinetics, thermodynamics underpin life processes.
  • The idea of homeostasis as a metabolic state maintained by feedback mechanisms.

Glossary

  • Metabolism: all biochemical reactions in an organism.
  • Anabolism: energy-consuming biosynthetic processes.
  • Catabolism: energy-releasing degradative processes.
  • ATP/ADP/AMP: adenine nucleotides that store and transfer energy.
  • NADH/FADH₂: electron carriers.
  • Glycolysis, Pyruvate oxidation, Krebs cycle, ETC: the major stages of glucose oxidation.

Common Scenarios and Examples

  • After a meal: glucose is abundant; glycolysis and glycogenesis are active; excess acetyl-CoA can feed into fatty acid synthesis.
  • During fasting: glycogenolysis and gluconeogenesis raise blood glucose; increased fatty acid oxidation for energy; ketone bodies produced in prolonged fasting.
  • Hypothetical metabolic adaptation: a person switches to a high-fat diet; increased beta-oxidation in liver and muscle; increased ketone body production during fasting.

Numerical References and Formulas

  • Glycolysis net equation: \text{Glucose} + 2\,NAD^+ + 2\,ADP + 2\,Pi \rightarrow 2\,\text{pyruvate} + 2\,NADH + 2\,ATP + 2\,H2O + 2\,H^+
  • Pyruvate oxidation yields: per glucose, 2\,NADH.
  • Krebs cycle per glucose: 6\,NADH + 2\,FADH2 + 2\,GTP + 4\,CO2
  • ATP yield (typical): \approx 30-32 \text{ ATP per glucose}
  • ATP hydrolysis energy: \Delta G_{ATP} \approx -50\,\text{kJ/mol} in cells