Citric-acid cycle, electron-transport chain, chemiosmosis, ATP synthase, bioenergetics.
Tca Oxphos
Citric acid cycle (Krebs / TCA)
Mitochondrial eight-step cycle oxidising acetyl-CoA to 2 CO2, producing 3 NADH + 1 FADH2 + 1 GTP per turn. Central hub feeding reducing…
Pyruvate dehydrogenase complex (PDC)
Multienzyme complex (E1/E2/E3, ~50 MDa) linking glycolysis to TCA: pyruvate + CoA + NAD+ → acetyl-CoA + CO2 + NADH. Regulated by…
Electron transport chain (ETC)
Series of inner-mitochondrial-membrane complexes (I, II, III, IV) transferring electrons from NADH/FADH2 to O2, pumping protons to…
ATP synthase (F0F1)
Rotary nano-motor coupling proton flow down the electrochemical gradient to ATP synthesis. F0 (membrane c-ring) rotates; F1 (α3β3)…
Chemiosmotic theory (Mitchell)
Mitchell 1961: respiratory electron transport couples to ATP synthesis via a transmembrane electrochemical proton gradient (proton-motive…
Proton-motive force (Δp)
Electrochemical potential for H+ across the inner mitochondrial membrane: Δp = Δψ − (2.303·RT/F)·ΔpH ≈ 200 mV (negative inside).
Oxidative phosphorylation
Coupled process: ETC pumps H+ → PMF → ATP synthase uses PMF to phosphorylate ADP. ~2.5 ATP per NADH, ~1.5 ATP per FADH2 (P/O ratios, Hinkle…
Uncoupling protein (UCP1/thermogenin)
Inner-membrane proton channel that dissipates PMF as heat without ATP synthesis. Abundant in brown adipose tissue; regulated by fatty…
Anaplerotic reactions
Reactions replenishing TCA intermediates drained for biosynthesis (amino acids, heme). Pyruvate carboxylase (pyruvate → oxaloacetate) is…
Respiratory supercomplexes
ETC complexes I, III, IV assemble into higher-order 'respirasomes' (I+III2+IV or I+III2+IV2). Channel substrates efficiently; dysregulation…
P/O ratio: oxidative-phosphorylation stoichiometry framework
P/O ratio: ATP synthesised per oxygen-atom consumed by mitochondrial electron-transport chain. Modern measurements: P/O = 2.5 for…
Mitchell chemiosmotic-coupling framework (1961)
Mitchell 1961 (Nature 191:144; 1978 Nobel): proton-motive-force Δp = ΔΨ – (2.3RT/F)·ΔpH (roughly 200 mV across inner mitochondrial membrane…
Krebs cycle (1937)
H Krebs 1937 (Nobel 1953) citric-acid-cycle; foundational text in biochemistry; reductive-TCA + glutaminolysis variants.
Chemiosmotic (Mitchell 1961)
P Mitchell 1961 (Nobel 1978) chemiosmotic-coupling; proton-gradient drives ATP-synthase; foundational bioenergetics.
ATP synthase (Boyer-Walker 1997)
Boyer-Walker Nobel 1997 ATP-synthase rotary mechanism; modern Yoshida-Kinosita rotation directly visualized.
Respiratory chain (Mitchell 1961)
Modern Complex-I-IV electron-transport-chain; Sazanov 2013 atomic-structure complex-I; modern OXPHOS supercomplexes Schagger 2000.
UCP (Nicholls 1976)
D Nicholls 1976 UCP1 brown-adipose; modern UCP2/3 + thermogenic-fat in humans Cypess 2009; obesity-target.
Randle cycle (1963)
P Randle 1963 glucose-fatty-acid cycle; modern metabolic-flexibility + insulin-resistance + diabetes-type-2.
Krebs cycle (Krebs 1937)
H Krebs 1937 (Nobel 1953) citric-acid-cycle; modern modern flux-control-coefficient + metabolic-control-analysis Kacser-Burns 1973.
Mitchell chemiosmotic (1961)
P Mitchell 1961 (Nobel 1978) chemiosmotic-coupling proton-gradient drives ATP-synthase; modern bioenergetic-orthodoxy.
ATP synthase (Walker 1994)
J Walker 1994 (Nobel 1997) F1F0 ATP-synthase rotary-mechanism; modern modern Yoshida + Noji direct rotation observation 1997.
Complex I (Rouslin 1969)
W Rouslin 1969 + Sazanov 2013 cryo-EM Complex-I; modern Q-cycle + supercomplex-organization mitochondrial-respirasome.
UCP1 (Nicholls 1976)
D Nicholls 1976 UCP1-thermogenin brown-adipose; modern modern UCP1+ beige-adipose + obesity-therapy via thermogenesis 2024 trials.
mtDNA (Anderson 1981)
S Anderson 1981 mtDNA-Cambridge sequence; modern modern OXPHOS-disease + maternal-inheritance + mitochondrial-Eve dating L0.