Cell Physiology/Part 2

⚡Cellular Energetics

Life requires a constant supply of energy. Cells capture, store, and transform energy through intricate metabolic pathways, with the mitochondrion serving as the powerhouse that converts nutrients into the universal energy currency: ATP.

🔋 ATP: The Universal Energy Currency

Adenosine triphosphate (ATP) is the primary energy carrier in all living cells. The hydrolysis of ATP releases ~7.3 kcal/mol(ΔG°' = -30.5 kJ/mol) of free energy that powers virtually all cellular work.

Uses of ATP

  • • Mechanical work (muscle contraction)
  • • Transport work (ion pumps)
  • • Chemical work (biosynthesis)
  • • Signaling (phosphorylation)

ATP Turnover

  • • Body contains ~50g ATP
  • • Daily turnover: ~40-75 kg!
  • • Half-life: ~1 minute
  • • Must be constantly regenerated

Key Equation

ATP + H₂O → ADP + Pᵢ + Energy
ΔG = -30.5 kJ/mol (standard conditions)

🔄Overview of Cellular Metabolism

PathwayLocationInputOutputATP Yield
GlycolysisCytoplasmGlucose2 Pyruvate, 2 NADH2 (net)
Pyruvate OxidationMito. matrix2 Pyruvate2 Acetyl-CoA, 2 NADH0
Citric Acid CycleMito. matrix2 Acetyl-CoA6 NADH, 2 FADH₂, 2 GTP2
Electron TransportInner mito. membraneNADH, FADH₂, O₂H₂O, ATP~26-28
Total (per glucose)~30-32 ATP

⚡Electron Transport Chain Simulator

Inner Mitochondrial MembraneIntermembrane Space (H⁺ accumulation)Mitochondrial MatrixINADHIIFADH₂QIIIcIVO₂→H₂OF₀F₁ATP!H⁺ gradient: 130

Substrate Levels

NADH:10
FADH₂:5
O₂:100%
ADP:50%

Apply Inhibitor

Output

Δψ (membrane):180 mV
ATP produced:32.5
P/O (NADH):~2.5
P/O (FADH₂):~1.5
Note: The ETC uses electron flow to pump protons, creating an electrochemical gradient (proton-motive force, Δp ≈ 200 mV) that drives ATP synthesis.

🧮ATP Yield Calculator

1
Total ATP Yield
~31 ATP
per 1 glucose

Breakdown:

Glycolysis (net):2 ATP
TCA (GTP/ATP):2 ATP
NADH → ETC:~25 ATP
FADH₂ → ETC:~3 ATP
Shuttle cost:-1 ATP
Efficiency: ~40% of glucose energy captured as ATP (686 kcal/mol glucose → ~226 kcal as ATP)

🔬Chemiosmotic Theory (Peter Mitchell, 1961)

Mitchell's revolutionary insight: electron transport creates a proton gradientacross the inner mitochondrial membrane, and this electrochemical gradient (proton-motive force, Δp) drives ATP synthesis.

Proton-Motive Force (Δp)

Δp = Δψ - (2.3RT/F)ΔpH
  • • Δψ ≈ 140-180 mV (electrical component)
  • • ΔpH ≈ 0.5-1 unit (chemical component)
  • • Total Δp ≈ 200 mV

ATP Synthase

  • • F₀ portion: membrane-embedded proton channel
  • • F₁ portion: catalytic domain (ATP synthesis)
  • • Rotary motor: ~100 revolutions/sec
  • • ~3-4 H⁺ per ATP synthesized
  • • Works as ATPase if gradient reverses!
Nobel Prize (1978): Mitchell won the Nobel Prize in Chemistry for the chemiosmotic theory, which unified our understanding of oxidative phosphorylation, photophosphorylation, and bacterial ATP synthesis.

🎛️Metabolic Regulation

Energy Charge

EC = ([ATP] + 0.5[ADP]) / ([ATP] + [ADP] + [AMP])

Energy charge reflects cellular energy status (normal: 0.85-0.95). High EC inhibits catabolic pathways; low EC stimulates them.

Key Regulatory Enzymes

  • •Hexokinase: Inhibited by G6P (product inhibition)
  • •PFK-1: Activated by AMP, F-2,6-BP; inhibited by ATP, citrate
  • •Pyruvate kinase: Activated by F-1,6-BP
  • •PDH complex: Inhibited by acetyl-CoA, NADH

Chapter Topics

2.1

Glycolysis

The universal pathway for glucose breakdown

2.2

Citric Acid Cycle

The metabolic hub for energy extraction

2.3

Electron Transport

Harnessing electron flow to pump protons

2.4

ATP Synthase

The rotary engine that makes ATP

2.5

Metabolic Integration

Coordination of pathways and regulation

←Part 1: Membrane & TransportPart 3: Cell Signaling→