Cellular Energetics: Citric Acid Cycle and ATP Synthesis

Citric Acid Cycle

Nine reactions oxidize acetyl CoA to CO2, producing NADH and FADH2.

Fatty Acid Oxidation

Oxidation of fatty acids in mitochondria for ATP production.

Pyruvate Dehydrogenation

Conversion of pyruvate to acetyl CoA, generating NADH and CO2.

NADH

High-energy electron carrier in oxidative phosphorylation.

FADH2

High-energy electron carrier in oxidative phosphorylation.

Electron Transport Chain

Series of complexes transferring electrons to generate ATP.

Proton-Motive Force

Established by electron transport chain to synthesize ATP.

Glycolysis

Glucose breakdown to pyruvate with ATP and NADH production.

Acetyl CoA

Two-carbon compound entering the citric acid cycle.

Oxaloacetate

Four-carbon compound combining with acetyl CoA in citric acid cycle.

ATP Synthase

Enzyme using proton-motive force to produce ATP.

Citrate

Six-carbon compound formed in the citric acid cycle.

Isocitrate

Isomer of citrate formed in the citric acid cycle.

α-Ketoglutarate

Five-carbon compound formed from isocitrate in the citric acid cycle.

Succinyl CoA

Compound formed from α-ketoglutarate in the citric acid cycle.

Succinate

Product of succinyl CoA oxidation in the citric acid cycle.

Fumarate

Product of succinate oxidation in the citric acid cycle.

Citrate Synthase

Enzyme catalyzing acetyl group transfer to oxaloacetate.

Aconitase

Enzyme converting citrate to isocitrate in the citric acid cycle.

Succinyl-CoA Synthase

Enzyme catalyzing substrate-level phosphorylation in the citric acid cycle.

FAD

Coenzyme converted to FADH2 in succinate oxidation.

NAD+

Coenzyme reduced to NADH in isocitrate and α-ketoglutarate oxidation.

GTP

Energy carrier formed in succinyl-CoA phosphorylation.

CO2

Waste product released in citric acid cycle reactions.

Flavin adenine dinucleotide (FAD)

Enzyme cofactor accepting two hydrogen atoms, reduced to FADH2

Malate

Dehydrogenated to oxaloacetate in Citric Acid Cycle

Endergonic reaction

Reaction with energy input (>+7 kcal/mol) to proceed forward

Citrate synthase

Enzyme maintaining low oxaloacetate concentrations

Pyruvate

Starting compound in the Citric Acid Cycle

NADH Shuttles

Mechanisms transferring cytosolic NADH into mitochondria

Glycerol-3-phosphate shuttle

Transfers NADH as FADH2 in complex II with energy cost

Malate-aspartate shuttle

Transfers NADH as NADH in complex I without energy cost

β oxidation

Process in mitochondria removing 2-carbon units from fatty acyl CoA

Flavoproteins

Contain FAD or FMN, capable of donating/accepting protons and electrons

Cytochromes

Contain heme prosthetic groups, alternating between Fe+2 and Fe+3

Iron-sulfur proteins

Contain iron linked to non-heme sulfur centers, accepting/donating electrons

Ubiquinone (coenzyme Q)

Lipid-soluble molecule with a long hydrophobic chain composed of five carbon isoprenoids, capable of rapid lateral diffusion, and can accept and donate 2 electrons and protons.

Ubisemiquinone

Partially reduced form of ubiquinone.

Ubiquinol

Fully reduced form of ubiquinone.

Proton-motive force

Energy stored as a combination of proton and voltage gradient across a membrane.

Complex I (NADH dehydrogenase complex)

Catalyzes the transfer of electron pairs from NADH to ubiquinone, translocating 4 protons with each pair of electrons through the complex.

Complex II (Succinate dehydrogenase complex)

Contains FAD, catalyzes reactions in the Citric Acid cycle generating FADH2, and transfers electrons to ubiquinone without proton transfer.

Complex III (Cytochrome bc1)

Accepts electrons from ubiquinol, passes them to cytochrome c, and transfers 4 protons with each electron pair through the complex.

Complex IV (Cytochrome oxidase)

Large assembly of polypeptides that removes 4 protons from the matrix for each pair of electrons, using 2 protons and electrons to reduce O2 to H2O.

Chemiosmotic hypothesis

States that the proton-motive force across the inner mitochondrial membrane is the immediate source of energy for ATP synthesis.

ATP synthase

Enzyme that both synthesizes and hydrolyzes ATP, consisting of F1 (catalytic subunit) and F0 (membrane-embedded unit) portions.

Binding Change Mechanism

States that movement of protons through ATP synthase alters the binding affinity of the active site, leading to ATP synthesis through rotational catalysis.

Substrate-level phosphorylation

Direct energy input into ATP synthesis by transferring a high-energy phosphate bond to ADP, occurring in glycolysis and the Citric Acid cycle.

Oxidative phosphorylation

Indirect energy input into ATP synthesis, occurring through chemiosmosis powered by the electron transport chain.

Glycolysis net equation

Glucose + 2 ADP + 2 Pi + 2 NAD+ → 2 pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O.

Malate-Aspartate shuttle

Electrons from NADH in glycolysis are transferred to complex I of the electron transport chain, yielding 38 ATP per glucose, active in heart and liver tissue.

Prokaryotic cells ATP production

Oxidative phosphorylation associated with the cell membrane, with electrons from NADH in glycolysis transferred directly to the electron transport chain.

Cytochrome c

Peripheral protein associated with the surface facing the intermembrane space, acting as a mobile carrier between complex III and IV.