The TCA (Krebs / Citric Acid) Cycle — 8 enzymes, all available
Citrate synthase (CS)
Acetyl-CoA + OAA → Citrate + CoA-SH
Irreversible gate of the cycle. Asp375 enolizes acetyl-CoA; Claisen condensation onto OAA, then thioester hydrolysis. Inhibited by ATP / NADH.
EC 2.3.3.1 · PDB 5CTS
▶ OPEN SIMULATORAconitase (ACO)
Citrate ⇌ Isocitrate (via cis-aconitate)
[4Fe-4S] cluster coordinates the substrate. Ser642 base / His101 acid: dehydration to cis-aconitate then stereo-specific rehydration → isocitrate.
EC 4.2.1.3 · PDB 1ACO
▶ OPEN SIMULATORIsocitrate dehydrogenase (NAD⁺ IDH3)
Isocitrate + NAD⁺ → α-KG + CO₂ + NADH
First oxidative decarboxylation. Hydride to NAD⁺ → oxalosuccinate, then metal-assisted decarboxylation to α-KG + CO₂.
EC 1.1.1.41 · PDB 6KDY
▶ OPEN SIMULATORα-Ketoglutarate DH complex (OGDH)
α-KG + CoA + NAD⁺ → Succinyl-CoA + CO₂ + NADH
PDH-like E1/E2/E3 machine. TPP decarboxylates α-KG; the lipoyl swinging arm carries the succinyl group; E3 makes NADH. Second CO₂ + NADH.
EC 1.2.4.2 · 2.3.1.61 · 1.8.1.4 · PDB 8I0K
▶ OPEN SIMULATORSuccinyl-CoA synthetase (SCS)
Succinyl-CoA + GDP + Pi → Succinate + GTP + CoA-SH
Substrate-level phosphorylation. Catalytic His299 cycles His ⇄ phospho-His; thioester energy drives GTP synthesis from GDP + Pi.
EC 6.2.1.4 · PDB 2FP4
▶ OPEN SIMULATORSuccinate dehydrogenase (SDH · Complex II)
Succinate + FAD → Fumarate + FADH₂
Membrane-bound, FAD-linked. His365 abstracts a proton; hydride to N5. FADH₂ feeds electrons via Fe-S clusters to ubiquinone (ETC).
EC 1.3.5.1 · PDB 1ZOY
▶ OPEN SIMULATORFumarase (fumarate hydratase · FH)
Fumarate + H₂O → L-Malate
Stereospecific anti-addition of water. RTHTQ loop: His235 is the water-activating residue (M-CSA 569). Fully reversible lyase.
EC 4.2.1.2 · PDB 5UPP
▶ OPEN SIMULATORMalate dehydrogenase (MDH2)
L-Malate + NAD⁺ → OAA + NADH + H⁺
Cycle-closing oxidation. His182 ★ abstracts the 2-OH proton; hydride from malate C2 to nicotinamide C4. The OAA regenerated starts the next turn.
EC 1.1.1.37 · PDB 2DFD
▶ OPEN SIMULATOR