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Catabolic Pathways
Glucose oxidation: Glycolysis: glucose → 2 pyruvate; net 2 ATP + 2 NADH (cytoplasm). Pyruvate decarboxylation: 2 acetyl-CoA; 2 NADH. Krebs cycle (×2): 6 NADH + 2 FADH₂ + 2 GTP. Oxidative phosphorylation: NADH → ~2.5 ATP; FADH₂ → ~1.5 ATP. Total: ~30–32 ATP per glucose. Fat oxidation (β-oxidation): highly efficient; palmitate → ~106 ATP. Protein: amino acid catabolism → enters at pyruvate, acetyl-CoA, or Krebs intermediates.
Anabolic Pathways
- Gluconeogenesis: non-carbohydrate precursors → glucose; occurs in liver/kidney
- Fatty acid synthesis: acetyl-CoA → fatty acids; uses NADPH; in cytoplasm
- Protein synthesis: translation (ribosome); uses ATP and GTP
Metabolic Regulation
Allosteric regulation: AMP, ADP → activate AMPK → stimulates catabolism; ATP → inhibits. Hormonal: insulin → anabolism; glucagon → catabolism; cortisol → catabolism. Substrate availability: glucose, fatty acid concentrations drive pathway selection.
Glossary
Frequently Asked Questions
Metabolism is the total of all biochemical reactions in a living cell or organism. Catabolism: reactions that break down complex molecules into simpler ones; releases energy; produces ATP, NADH, FADH₂. Examples: glycolysis, Krebs cycle, β-oxidation of fatty acids, amino acid catabolism. Anabolism: reactions that build complex molecules from simpler precursors; requires energy (ATP, NADPH, reducing equivalents). Examples: protein synthesis, DNA replication, fatty acid synthesis, gluconeogenesis, glycogen synthesis. The two divisions are coupled: catabolism provides the ATP and reducing power (NADPH) needed for anabolism.
Glycolysis (Embden-Meyerhof-Parnas pathway): occurs in the cytoplasm; anaerobic (no O₂ required). Steps: 10 enzyme-catalyzed reactions convert 1 glucose (6C) to 2 pyruvate (3C). Net yield: 2 ATP (consumed 2, produced 4 = net +2); 2 NADH; 2 pyruvate. Under aerobic conditions: pyruvate → acetyl-CoA → Krebs cycle → oxidative phosphorylation → full ATP yield ~30. Under anaerobic conditions: pyruvate → lactate (in animals/yeast → ethanol); regenerates NAD⁺ to sustain glycolysis; only 2 ATP from glucose. Rate-limiting enzyme: phosphofructokinase-1 (PFK-1); allosterically activated by AMP, ADP, fructose-2,6-bisphosphate; inhibited by ATP and citrate.
Oxidative phosphorylation (OXPHOS): occurs on the inner mitochondrial membrane; the main ATP-producing pathway. Steps: NADH and FADH₂ from glycolysis, PDC, and Krebs donate electrons to Complex I/II of the electron transport chain (ETC). Electrons flow through Complexes I→III→IV; final acceptor is O₂ → H₂O. Complexes I, III, IV pump H⁺ across the inner membrane → creates proton motive force (PMF) = ΔΨ + ΔpH. H⁺ flows back through ATP synthase (Complex V) → drives ATP synthesis from ADP + Pᵢ. Yield: each NADH → ~2.5 ATP (P/O ratio); each FADH₂ → ~1.5 ATP. Total from glucose oxidation: ~30–32 ATP. Uncoupling: protons bypass ATP synthase (via UCP1 in brown adipose tissue) → dissipated as heat.
Metabolic regulation ensures ATP production matches demand and prevents futile cycling: Allosteric regulation: immediate, reversible regulation of enzyme activity by metabolites. Phosphofructokinase-1 (glycolysis): inhibited by high ATP and citrate; activated by AMP and ADP. Pyruvate kinase: activated by fructose-1,6-bisphosphate; inhibited by ATP and alanine. AMPK (AMP-activated protein kinase): activated by high AMP/ATP ratio (energy shortage) → stimulates catabolism; inhibits anabolism. Hormonal regulation: Insulin: released after carbohydrate intake; activates glucose uptake (GLUT4), glycolysis, glycogen synthesis, fatty acid synthesis. Glucagon: released during fasting; activates gluconeogenesis, glycogenolysis, fatty acid oxidation. Cortisol: stress hormone; promotes protein catabolism and gluconeogenesis.