Citric Acid Cycle and Oxidative Phosphorylation (1D) - MCAT Biological and Biochemical Foundations of Living Systems

Intermembrane space $ ightarrow$ matrix. Protons flow down their electrochemical gradient from intermembrane space to matrix, driving ATP synthase's conformational changes for ATP production.

$9.0$ ATP. Each NADH yields approximately 2.5 ATP and each FADH$_2$ yields 1.5 ATP through oxidative phosphorylation efficiency.

Aconitase. Aconitase isomerizes citrate to isocitrate through cis-aconitate intermediate, preparing for subsequent decarboxylation.

Isocitrate dehydrogenase. This enzyme catalyzes the rate-limiting oxidative decarboxylation of isocitrate to $alpha$-ketoglutarate, generating NADH and releasing CO$_2$.

$ ext{alpha}$-ketoglutarate dehydrogenase complex. The complex performs oxidative decarboxylation, analogous to pyruvate dehydrogenase, producing succinyl-CoA, NADH, and CO$_2$.

Succinyl-CoA synthetase (succinate thiokinase). This enzyme cleaves the thioester bond of succinyl-CoA, coupling it to phosphorylation of GDP to GTP or ADP to ATP.

Succinate dehydrogenase (Complex II). As part of the ETC, this enzyme oxidizes succinate to fumarate, reducing FAD to FADH$_2$ for electron transfer.

Malate dehydrogenase. This enzyme regenerates oxaloacetate by oxidizing malate, reducing NAD$^+$ to NADH in the final step of the cycle.

$6$ NADH and $2$ FADH$_2$. Two acetyl-CoA from one glucose enter two cycles, each producing 3 NADH and 1 FADH$_2$, totaling these carriers.

$1$ acetyl-CoA, $1$ NADH, $1$ CO$_2$. Pyruvate is oxidatively decarboxylated, yielding acetyl-CoA for the TCA cycle, NADH as an electron carrier, and CO$_2$ as a byproduct.

Mitochondrial matrix. The citric acid cycle occurs in the mitochondrial matrix where enzymes and substrates are concentrated for efficient metabolic processing.

ATP synthase (Complex V). ATP synthase harnesses the proton gradient's energy via rotational catalysis to phosphorylate ADP to ATP.

ETC stops, NADH accumulates, ATP synthase halts. Without O$_2$ as terminal acceptor, electron flow halts, preventing NADH oxidation and proton gradient maintenance for ATP synthesis.

Citrate synthase. This enzyme catalyzes the irreversible condensation reaction, committing acetyl-CoA to the citric acid cycle.

Fumarase (fumarate hydratase). Fumarase adds water across the double bond of fumarate, stereospecifically forming L-malate in a reversible hydration reaction.

$3$ NADH, $1$ FADH$_2$, $1$ GTP, $2$ CO$_2$. One acetyl-CoA through the cycle yields reduced cofactors for ETC, GTP for energy, and CO$_2$ as waste.

Create a proton-motive force by pumping H$^+$. The ETC transfers electrons from reduced carriers to O$_2$, using energy to pump protons and establish a gradient for ATP synthesis.

O$_2$ (reduced to H$_2$O). Oxygen accepts electrons from cytochrome c oxidase, forming water and preventing electron backup in the chain.

Complexes I, III, and IV. These complexes use electron transfer energy to translocate protons into the intermembrane space, creating the electrochemical gradient.

Complex I (NADH dehydrogenase). Complex I oxidizes NADH to NAD$^+$, transferring electrons to ubiquinone while pumping protons across the membrane.

Complex II (succinate dehydrogenase). Complex II directly feeds electrons from FADH$_2$ into the ubiquinone pool without pumping protons itself.

Coenzyme Q (ubiquinone) and cytochrome $c$. These carriers facilitate electron transfer: ubiquinone between I/II and III, cytochrome c between III and IV.

Oxaloacetate. Oxaloacetate serves as the acceptor for the acetyl group from acetyl-CoA, initiating the cycle by forming citrate.