Cellular Energetics and Metabolism

Cellular Energetics and Metabolism

Cellular Energetics and Metabolism

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Bioenergetics & ATP - Energy's Opening Act

  • Bioenergetics: Study of energy flow in biological systems.
    • 1st Law Thermodynamics: Energy is conserved.
    • 2nd Law Thermodynamics: Universe favors ↑ entropy (disorder).
  • Gibbs Free Energy (${\Delta G}$): Predicts reaction spontaneity.
    • ${\Delta G < 0}$: Exergonic (releases energy). 📌 EXergonic EXits energy.
    • ${\Delta G > 0}$: Endergonic (requires energy).
  • ATP (Adenosine Triphosphate): Universal cellular energy currency (Adenine, Ribose, 3 Phosphates).
    • Hydrolysis of terminal phosphate bonds releases ~-7.3 kcal/mol (or ~-30.5 kJ/mol).

    ⭐ A resting human consumes ~40 kg of ATP in 24 hours, but the body only contains ~50g at any moment due to rapid turnover. oka

Glycolysis - Sugar Split Story

  • Cytosolic pathway breaking down Glucose (1x6C) into 2 Pyruvate (2x3C). Occurs in all cells; anaerobic.
  • Two Phases:
    • Preparatory (Investment): Consumes 2 ATP. Glucose $\rightarrow$ Fructose-1,6-bisphosphate.
    • Payoff (Generation): Produces 4 ATP, 2 NADH. Fructose-1,6-bisphosphate $\rightarrow$ 2 Pyruvate.
  • Net Yield (per glucose): 2 ATP, 2 NADH, 2 Pyruvate.
  • Key Regulatory Enzyme: Phosphofructokinase-1 (PFK-1).
    • Activated by: AMP, Fructose-2,6-bisphosphate (most potent).
    • Inhibited by: ATP, Citrate.
  • 📌 Irreversible enzymes: Hexokinase/Glucokinase, PFK-1, Pyruvate Kinase.
  • Fates of Pyruvate: Aerobic $\rightarrow$ Acetyl-CoA; Anaerobic $\rightarrow$ Lactate or Ethanol.

⭐ In erythrocytes, glycolysis is the sole ATP source. 2,3-BPG, a glycolytic intermediate, modulates hemoglobin's oxygen affinity.

Krebs Cycle & PDC - Metabolic Merry-Go-Round

Pyruvate Dehydrogenase Complex (PDC): Links glycolysis to Krebs.

  • Location: Mitochondrial matrix.
  • Reaction: $Pyruvate + CoA + NAD^+ \rightarrow Acetyl\text{-}CoA + CO_2 + NADH + H^+$
  • Cofactors (5): 📌 Tender Loving Care For Nancy (Thiamine, Lipoate, CoA, FAD, NAD).

Krebs Cycle (TCA/Citric Acid Cycle): Central metabolic hub.

  • Location: Mitochondrial matrix.
  • Entry: Acetyl-CoA + Oxaloacetate $\rightarrow$ Citrate.
  • Yields per Acetyl-CoA:
    • 3 $NADH$ (→ 9 ATP)
    • 1 $FADH_2$ (→ 2 ATP)
    • 1 $GTP$ (or $ATP$)
    • 2 $CO_2$
  • Net ATP: 12 per Acetyl-CoA (aerobic).
  • Intermediates Mnemonic: 📌 Citrate Is Krebs' Starting Substrate For Making Oxaloacetate.

Cellular Energetics Pathways Overview

⭐ The enzyme $\alpha$-ketoglutarate dehydrogenase in the Krebs cycle uses the same 5 cofactors as Pyruvate Dehydrogenase Complex (PDC).

ETC & Oxidative Phosphorylation - ATP Factory Finale

  • Site: Inner mitochondrial membrane.
  • Process: NADH & FADH2 are oxidized. Electrons flow through ETC complexes to O2 (final acceptor), forming H2O. This pumps H+ from matrix to intermembrane space (IMS).
  • Chemiosmosis: H+ gradient (proton-motive force) across IMS drives ATP synthesis as H+ returns to matrix via ATP Synthase (Complex V).
  • Key Components:
    • Complexes I, II, III, IV: Sequential electron transfer & H+ pumping (I, III, IV).
    • Coenzyme Q (Ubiquinone) & Cytochrome c: Mobile e- carriers.
  • ATP Yield: NADH $\approx$ 2.5 ATP; FADH2 $\approx$ 1.5 ATP.
  • Inhibitors: Rotenone, Amytal (Complex I); Antimycin A (Complex III); Cyanide (CN-), CO, Azide (N3-) (Complex IV); Oligomycin (ATP Synthase).
  • Uncouplers (e.g., DNP, Aspirin overdose, Thermogenin): Disrupt H+ gradient; ↑O2 consumption, ↓ATP synthesis, produce heat.

⭐ Cyanide blocks Complex IV (Cytochrome c oxidase), halting O2 utilization and aerobic ATP synthesis, leading to histotoxic hypoxia.

Electron Transport Chain and Oxidative Phosphorylation

High‑Yield Points - ⚡ Biggest Takeaways

  • ATP is the primary energy currency of the cell; its hydrolysis yields approximately 7.3 kcal/mol.
  • Glycolysis, occurring in the cytoplasm, is the anaerobic breakdown of glucose to pyruvate, netting 2 ATP and 2 NADH.
  • The TCA cycle (Krebs cycle) occurs in the mitochondrial matrix under aerobic conditions, generating ATP (via GTP), NADH, FADH2, and CO2.
  • Oxidative phosphorylation on the inner mitochondrial membrane, involving the electron transport chain (ETC) and chemiosmosis, produces the majority of cellular ATP.
  • Uncoupling agents like DNP and thermogenin (UCP1) dissipate the proton gradient, inhibiting ATP synthesis and generating heat.
  • Gluconeogenesis is the synthesis of new glucose from non-carbohydrate precursors such as lactate, glycerol, and specific amino acids.
  • The Cori cycle involves the transport of lactate from muscle to the liver for gluconeogenesis, and glucose back to muscle.
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Practice Questions: Cellular Energetics and Metabolism

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Which enzyme in the Krebs cycle is indirectly affected by hyperammonemia due to its impact on metabolic pathways?

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Flashcards: Cellular Energetics and Metabolism

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What kind of transport systems follow stereospecificity?_____

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What kind of transport systems follow stereospecificity?_____

Carrier-mediated

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