Citric Acid Cycle and Oxidative Phosphorylation Vocabulary

Vocabulary terms, definitions, regulatory enzymes, inhibitors, and clinical conditions related to the pyruvate dehydrogenase complex, citric acid cycle, and oxidative phosphorylation.

Mitochondrial Structure

The cellular organelle bounded by a porous outer membrane, an inner membrane impermeable to most molecules with cristae to expand surface area, an intermembrane space, and an internal matrix housing enzymes, mtDNA, and ribosomes.

Cristae

Infoldings of the inner mitochondrial membrane that function to increase total surface area for metabolic processes.

Mitochondrial Matrix

The space internal to the inner mitochondrial membrane where mitochondrial DNA, ribosomes, and soluble metabolic enzymes are located.

Pyruvate Dehydrogenase Complex (PDH Complex)

A multienzyme complex located in the mitochondrial matrix that converts pyruvate to acetyl $\text{CoA}$ via oxidative decarboxylation, releasing $\text{CO}_2$ and generating $\text{NADH}$.

E1 (Pyruvate Decarboxylase)

The first enzyme component of the PDH complex that removes a carbon atom from pyruvate as $\text{CO}_2$, utilizing thiamine pyrophosphate ($\text{TPP}$) as its coenzyme.

E2 (Dihydrolipoyl Transacetylase)

The second enzyme component of the PDH complex that transfers the remaining two-carbon acetyl group to $\text{CoA}$ to form acetyl $\text{CoA}$, utilizing lipoic acid and $\text{CoA}$ as coenzymes.

E3 (Dihydrolipoyl Dehydrogenase)

The third enzyme component of the PDH complex that regenerates oxidized lipoic acid and forms $\text{NADH}$, utilizing $\text{FAD}$ and $\text{NAD}^+$ as coenzymes.

PDH Kinase

A regulatory enzyme that inactivates E1 of the PDH complex by phosphorylation; activated by high levels of acetyl $\text{CoA}$, $\text{NADH}$, and $\text{ATP}$, and inhibited by pyruvate and $\text{ADP}$.

PDH Phosphatase

A regulatory enzyme that activates the PDH complex by dephosphorylation; allosterically activated by calcium ions ($\text{Ca}^{2+}$).

Congenital Lactic Acidosis

A rare genetic condition commonly caused by an E1 subunit deficiency of the PDH complex, preventing conversion of pyruvate to acetyl $\text{CoA}$ and causing pyruvate to accumulate as lactate.

Thiamine (Vitamin B1) Deficiency

A nutritional deficiency that inactivates the PDH complex because its E1 enzyme requires thiamine pyrophosphate ($\text{TPP}$) as a coenzyme.

Arsenic Poisoning

Toxicity caused by arsenic binding to lipoic acid, preventing lipoic acid from functioning as an E2 coenzyme in the PDH complex.

Citrate Synthase

An enzyme in the citric acid cycle that catalyzes the initial step combining acetyl $\text{CoA}$ and oxaloacetate to form citric acid.

Isocitrate Dehydrogenase

The rate-limiting enzyme of the citric acid cycle that converts isocitrate to $\alpha$-ketoglutarate; allosterically activated by $\text{ADP}$ and $\text{Ca}^{2+}$ and inhibited by $\text{ATP}$ and $\text{NADH}$.

$\alpha$-Ketoglutarate Dehydrogenase Complex

A three-enzyme complex in the citric acid cycle that catalyzes the conversion of $\alpha$-ketoglutarate to succinyl $\text{CoA}$; activated by $\text{Ca}^{2+}$ and inhibited by succinyl $\text{CoA}$ and $\text{NADH}$.

Oxidative Phosphorylation

The cellular pathway comprising the electron transport chain and $\text{ATP}$ synthesis on the inner mitochondrial membrane to generate $\text{ATP}$ using an established proton gradient.

ETC Complex I (NADH Dehydrogenase)

The first complex of the electron transport chain that accepts electrons exclusively from $\text{NADH}$, pumps $4\,\text{H}^+$ into the intermembrane space, and transfers electrons to coenzyme Q.

ETC Complex II (Succinate Dehydrogenase)

An electron transport chain complex that accepts electrons exclusively from $\text{FADH}_2$ and transfers them to coenzyme Q without pumping protons or causing energy loss.

ETC Complex III (Cytochrome c Reductase)

The third complex of the electron transport chain that receives electrons from coenzyme Q, pumps $4\,\text{H}^+$ into the intermembrane space, and passes electrons to Cytochrome c.

ETC Complex IV (Cytochrome c Oxidase)

The final complex of the electron transport chain that receives electrons from Cytochrome c, pumps $2\,\text{H}^+$ into the intermembrane space, and passes final electrons to molecular oxygen to form $\text{H}_2\text{O}$.

Coenzyme Q (CoQ)

A mobile electron carrier within the inner mitochondrial membrane that transfers electrons from Complex I and Complex II to Complex III.

Cytochrome C

A mobile electron carrier protein that transports electrons from Complex III to Complex IV in the electron transport chain.

Proton-Motive Force

The potential energy stored in the electrochemical proton gradient created across the inner mitochondrial membrane by proton pumping at Complexes I, III, and IV.

$F_0$ Domain

The membrane-spanning channel domain of $\text{ATP}$ synthase on the inner mitochondrial membrane that rotates as protons flow back into the matrix.

$F_1$ Domain

The matrix-located domain of $\text{ATP}$ synthase that possesses catalytic activity to convert $\text{ADP}$ and $\text{P}_i$ into $\text{ATP}$ upon domain rotation.

ADP/ATP Translocase

An antiporter on the inner mitochondrial membrane that pumps $\text{ATP}$ out into the intermembrane space while pumping $\text{ADP}$ into the matrix.

Rotenone

A pesticide that acts as an electron transport chain inhibitor by specifically targeting Complex I.

Antimycin A

An antibiotic that inhibits the electron transport chain by specifically targeting Complex III.

Cyanide ($\text{CN}^-$)

An inhibitor of the electron transport chain that targets Complex IV, halting final electron transfer to oxygen.

Oligomycin

An inhibitor of $\text{ATP}$ synthesis that binds to the $F_0$ domain of $\text{ATP}$ synthase and closes the proton channel.

Thermogenin (Uncoupling Protein 1 / UCP1)

An uncoupling protein found in brown adipocytes that forms a membrane channel allowing protons to re-enter the matrix, dissipating the proton gradient as heat rather than producing $\text{ATP}$.

2,4-Dinitrophenol (DNP)

A synthetic uncoupling agent that dissipates the mitochondrial proton gradient across the inner membrane, uncoupling electron transport from $\text{ATP}$ synthesis.

Ophthalmoplegia

Paralysis or weakness of eye muscles occurring in mitochondrial disorders, leading patients to turn their head instead of moving their eyes to view objects.

Ptosis

Drooping of the upper eyelid, commonly seen as a clinical sign of mitochondrial disorder due to energy failure in eye muscles.

Dysphagia

An oral muscle-related condition defined by difficulty in swallowing, often caused by tissue energy failure in mitochondrial disorders.

Dysarthria

An oral condition defined by impaired speech execution stemming from muscle weakness in patients with mitochondrial dysfunction.