Aerobic Respiration, the Endomembrane System, and Protein Sorting

Comprehensive vocabulary flashcards covering the biochemical pathways of aerobic cellular respiration (mitochondrial electron transport, citric acid cycle, ATP synthase) and the mechanisms of the eukaryotic endomembrane system (ER, Golgi complex, protein sorting, vesicle trafficking, lysosomes, and peroxisomes).

Cellular Respiration

The flow of electrons through or within a membrane, from reduced coenzymes to an external electron acceptor, usually accompanied by the generation of $ATP$ and the complete oxidation of substrates to $CO_2$.

External Electron Acceptor

A terminal electron acceptor in cellular respiration that is not a by-product of glucose catabolism.

Aerobic Respiration

A form of cellular respiration where the terminal electron acceptor is oxygen ($O_2$), which is reduced to water ($H_2O$), having the potential to yield up to $38\text{ ATP}$ molecules per glucose.

Anaerobic Respiration

A mode of respiration used by bacteria and archaea utilizing non-oxygen external electron acceptors, such as sulfur, protons, or ferric ions; distinct from fermentation.

Porins (Mitochondrial)

Transmembrane channel proteins located in the outer mitochondrial membrane that permit the passage of solutes with molecular weights up to $5000$.

Inner Mitochondrial Membrane

The mitochondrial membrane that is approximately $75\%$ protein by weight and functions in electron transport, proton translocation, oxidative phosphorylation, and metabolite import.

Pyruvate Dehydrogenase (PDH) Complex

A massive multienzyme complex (molecular weight approximately $4.6\text{ million}$) consisting of 3 catalytic enzymes, 5 coenzymes, and 2 regulatory proteins that converts pyruvate to acetyl CoA via oxidative decarboxylation.

Citric Acid Cycle (TCA Cycle / Krebs Cycle)

A central metabolic cycle of eight steps that completes the oxidation of acetyl groups derived from acetyl CoA to $CO_2$, producing reducing power in the form of $NADH$ and $FADH_2$, along with one $ATP$ or $GTP$.

Citrate Synthase

The enzyme that catalyzes reaction CAC-1, transferring the two-carbon acetate group from acetyl CoA to four-carbon oxaloacetate to form six-carbon citrate.

Succinate Dehydrogenase

The inner mitochondrial membrane enzyme that catalyzes reaction CAC-6, oxidizing succinate to fumarate by transferring two electrons from a $C=C$ bond to $FAD$.

PDH Kinase

A regulatory enzyme activated by $ATP$ that allosterically phosphorylates and inactivates the pyruvate dehydrogenase complex when the $[ATP]/[ADP]$ ratio is high.

PDH Phosphatase

A regulatory enzyme that activates the pyruvate dehydrogenase complex by dephosphorylation when the $[ATP]/[ADP]$ ratio is low.

$\beta$-Oxidation

A catabolic pathway confined to mitochondria that sequentially removes two-carbon units from a fatty acyl CoA to generate acetyl CoA, $NADH$, and $FADH_2$.

Ketosis

A physiological state resulting from excessive fat breakdown that depletes free coenzyme A and causes the accumulation of partial oxidation products known as ketone bodies.

Ketoacidosis

A pathological drop in blood pH caused by the high accumulation of acidic ketone bodies in the circulation, commonly occurring in untreated diabetes.

Standard Reduction Potential ($E_0'$)

A measure, in volts, of the affinity of a biological redox pair for electrons under standard conditions, relative to the reference reaction $2H^+ + 2e^- \rightarrow H_2$ ($0.00\,V$ at pH 0.0; $-0.42\,V$ at pH 7.0).

Coenzyme Q (Ubiquinone / CoQ)

A lipid-soluble quinone derivative that functions as the only non-protein electron carrier in the electron transport chain, freely diffusing through the plane of the inner mitochondrial membrane.

Complex I (NADH-Coenzyme Q Oxidoreductase)

A respiratory assembly composed of 43 polypeptides, 1 $FMN$, and 6–9 $Fe\text{-}S$ centers that transfers $2\,e^-$ from $NADH$ to CoQ and pumps $4\,H^+$ out of the matrix.

Complex II (Succinate-Coenzyme Q Oxidoreductase)

A respiratory complex composed of 4 polypeptides, 1 $FAD$, and 3 $Fe\text{-}S$ centers that transfers electrons from succinate to CoQ without pumping protons across the membrane.

Complex III (Coenzyme Q-Cytochrome c Oxidoreductase)

A respiratory complex composed of 11 polypeptides, 2 cytochrome $b$ proteins, 1 cytochrome $c_1$, and 1 $Fe\text{-}S$ center that passes electrons from $CoQH_2$ to cytochrome $c$ and translocates $4\,H^+$ into the intermembrane space.

Complex IV (Cytochrome c Oxidase)

A terminal respiratory complex composed of 13 polypeptides, cytochromes $a$ and $a_3$, and 2 copper centers that transfers electrons to $O_2$ to form $H_2O$, while pumping $2\,H^+$ from the matrix.

Respiratory Control

The physiological mechanism by which the concentration of $ADP$ regulates the rate of electron transport and oxidative phosphorylation in mitochondria.

Chemiosmotic Coupling Model

The model proposed by Peter Mitchell in 1961 stating that the electrochemical proton gradient across a membrane couples electron transport to ATP synthesis.

$F_o$ Complex

The hydrophobic, oligomycin-sensitive transmembrane component of ATP synthase embedded in the inner mitochondrial membrane, comprising subunits $a$, $b_2$, and a rotating ring of $10\,c$ subunits that translocates protons.

$F_1$ Complex

The peripheral catalytic complex of ATP synthase extending into the mitochondrial matrix, composed of an $\alpha_3\beta_3$ hexameric headpiece, a central $\gamma\epsilon$ stalk, and a $\delta$ stalk.

Binding-Change Model

Paul Boyer's 1979 model describing ATP synthesis, wherein the physical rotation of the $\gamma$ subunit forces each of the three $\beta$ catalytic subunits to sequentially cycle through Open (O), Loose (L), and Tight (T) conformations.

Rough Endoplasmic Reticulum (RER)

A membrane-bound organelle studded with ribosomes on its cytosolic surface, dedicated to cotranslational protein import, initial N-glycosylation, folding, and quality control of secretory and membrane proteins.

Smooth Endoplasmic Reticulum (SER)

A network of tubular ER membranes lacking ribosomes that functions in drug detoxification, steroid biosynthesis, carbohydrate metabolism, and calcium storage.

Molecular Chaperones

Proteins, such as the Hsp70 and Hsp60 families, that facilitate the correct folding of nascent or denatured polypeptides and prevent inappropriate protein aggregation.

BiP (Binding Protein)

An abundant ER-luminal member of the Hsp70 chaperone family that binds hydrophobic regions of polypeptides, prevents aggregation, and drives posttranslational protein import using ATP hydrolysis.

Unfolded Protein Response (UPR)

A cellular stress response pathway that uses sensors in the ER membrane to detect misfolded proteins, resulting in reduced general translation and increased transcription of chaperones and degradation machinery.

ER-Associated Degradation (ERAD)

A quality control pathway that identifies misfolded or unassembled proteins in the ER and retrotranslocates them to the cytosol for ubiquitination and degradation by proteasomes.

Proteasome

A large cylindrical protein complex of approximately $720\text{ kDa}$ located in the cytosol or nucleus that recognizes and degrades ubiquitin-tagged proteins into short peptides.

Cytochrome P-450

A superfamily of smooth ER monooxygenases that catalyzes the hydroxylation of hydrophobic drugs and xenobiotics to increase their water solubility for excretion.

Drug Tolerance

The reduced physiological response to a pharmacological agent caused by the proliferation of smooth ER and an increase in its drug-detoxifying enzymes following chronic administration.

Glucose-6-Phosphatase

An enzyme anchored in the smooth ER membrane of liver cells that removes the phosphate group from glucose-6-phosphate, producing free glucose that can exit the cell into the bloodstream.

Phospholipid Translocators (Flippases)

Membrane-bound enzymes that transfer specific phospholipids from the cytosolic monolayer to the luminal monolayer of the ER, generating lipid bilayer asymmetry.

Phospholipid Exchange Proteins

Cytosolic proteins that bind and transport individual phospholipid molecules from the ER across the cytosol to organelles such as mitochondria, chloroplasts, and peroxisomes.

Cis-Golgi Network (CGN)

The cisternal face of the Golgi complex oriented toward the rough ER that receives transition vesicles containing newly synthesized proteins and lipids.

Trans-Golgi Network (TGN)

The cisternal compartment on the exit face of the Golgi apparatus where proteins and lipids are sorted and packaged into secretory or transport vesicles destined for lysosomes, endosomes, or the cell surface.

Anterograde Transport

The directional vesicular movement of membrane lipids and proteins from the ER forward through the Golgi stacks toward the plasma membrane.

Retrograde Transport

The retrieval flow of vesicles from Golgi cisternae back to the ER to recycle lipids and membrane proteins and maintain organelle balance.

N-Linked Glycosylation

The addition of a preassembled core oligosaccharide to the nitrogen atom of a specific asparagine residue on a nascent polypeptide, initiated in the ER.

O-Linked Glycosylation

The posttranslational attachment of oligosaccharide units to the oxygen atom of the hydroxyl group on specific serine or threonine residues.

Dolichol Phosphate

A polyprenol lipid carrier embedded in the ER membrane that serves as the foundation for the step-by-step cytoplasmic assembly of the core oligosaccharide during N-linked glycosylation.

Preproinsulin

The full-length primary translation product of insulin that is converted to mature insulin through the successive cleavage of an N-terminal pre-sequence, formation of disulfide bonds, and removal of internal pro-amino acids.

Cotranslational Import

The mechanism by which ribosomes synthesizing proteins targeted for the endomembrane system or secretion attach to the rough ER membrane and thread the nascent chain across the bilayer during translation.

Posttranslational Import

The uptake of completed polypeptides synthesized on free cytosolic ribosomes into organelles like the nucleus, mitochondria, chloroplasts, and peroxisomes via organelle-specific targeting signals.

Signal Recognition Particle (SRP)

A cytosolic ribonucleoprotein complex consisting of six proteins and an RNA molecule that recognizes an N-terminal ER signal sequence, arrests translation, and docks the ribosome to an SRP receptor on the ER membrane.

Stop-Transfer Sequence

A sequence of hydrophobic amino acids within a nascent polypeptide that halts translocation through the translocon pore and moves laterally into the lipid bilayer to form a transmembrane $\alpha$-helix.

KDEL Sequence

A conserved C-terminal amino acid retrieval tag (Lys-Asp-Glu-Leu) present on soluble ER-resident proteins that directs their return from the Golgi back to the ER via retrograde transport.

RXR Retention Tag

An Arg-X-Arg amino acid motif (where X is any amino acid) that functions as a retention signal to keep proteins localized within the endoplasmic reticulum.

Mannose-6-Phosphate (M6P) Tag

A phosphorylated carbohydrate modification generated in the Golgi apparatus that targets soluble acid hydrolases to late endosomes and lysosomes by binding to mannose-6-phosphate receptors.

Transit Sequence

An N-terminal targeting peptide that directs posttranslationally imported proteins synthesized in the cytosol to mitochondria or chloroplasts, cleaved inside the organelle by transit peptidase.

Constitutive Secretion

Continuous, unregulated exocytosis of transport vesicles that fuse directly with the plasma membrane without requiring external triggers or signals, such as mucus secretion by intestinal lining.

Regulated Secretion

The selective release of secretory proteins from mature granules stored near the plasma membrane that fuse only upon receiving a specific extracellular signal, typically involving a transient elevation in intracellular $Ca^{2+}$.

Polarized Secretion

The spatial restriction of exocytosis to a defined surface or domain of a cell, exemplified by pancreatic acinar cells releasing digestive enzymes exclusively toward the pancreatic duct lumen.

SNARE Proteins

Complementary membrane-associated proteins (v-SNARE on transport vesicles and t-SNARE on target membranes) whose coiled-coil pairing promotes membrane fusion.

Dynamin

A cytosolic GTPase that forms helical rings around the neck of budding clathrin-coated pits, using GTP hydrolysis to constrict and pinch off the coated vesicle from the plasma membrane.

Clathrin Triskelion

The three-legged multimeric structural building unit of clathrin coats, composed of three clathrin heavy chains and three light chains radiating from a central vertex.

Transcytosis

The intracellular transport process wherein internalized receptor-ligand complexes are ferried across the cytoplasm in transport vesicles and secreted at an opposite plasma membrane domain.

Lysosome

A single membrane-enclosed organelle (~$0.5\,\mu m$ diameter) containing acid phosphatase and other acid hydrolases that functions at pH $4.0\text{--}5.0$ to degrade all major biological macromolecules.

Heterophagic Lysosome

A lysosome engaged in the degradation of extracellular materials ingested by phagocytosis or receptor-mediated endocytosis.

Autophagic Lysosome

A lysosome responsible for the digestion of intracellular components and obsolete or damaged organelles that originated inside the cell itself.

Macrophagy

A form of autophagy wherein an entire damaged organelle is wrapped in a double membrane derived from the endoplasmic reticulum to form an autophagosome prior to lysosomal fusion.

Acrosome

A specialized lysosome found at the head of a sperm cell that undergoes regulated exocytosis to discharge hydrolytic enzymes capable of digesting the egg's outer protective coatings during fertilization.

Peroxisome

A single membrane-bound eukaryotic organelle characterized by the presence of catalase for decomposing hydrogen peroxide ($H_2O_2$), and enzymes for fatty acid oxidation, amino acid catabolism, and detoxification.

Crystalline Cores (Peroxisomal)

Dense paracrystalline protein arrays commonly observed within animal peroxisomes on electron micrographs, consisting of highly concentrated metabolic enzymes such as urate oxidase.

Catalase

A heme-containing antioxidant enzyme in peroxisomes that detoxifies toxic hydrogen peroxide by decomposing it into molecular oxygen and water via the reaction $2H_2O_2 \rightarrow O_2 + 2H_2O$.