Iron Metabolism, Apoptosis, and Cell Cycle Regulation

Vocabulary flashcards covering key terms and concepts in Iron Metabolism, Apoptosis, and Regulation of the Cell Cycle.

Ferritin

The primary intracellular iron storage protein that stores iron in its ferric state ($Fe^{3+}$), holding up to $4500$ $Fe^{3+}$ ions per protein complex.

Transferrin (Tf)

The main plasma transport protein that binds ferric iron ($Fe^{3+}$) in the bloodstream and delivers it to target tissues via transferrin receptor-mediated endocytosis.

Ferroportin

The only known cellular iron exporter, responsible for transporting ferrous iron ($Fe^{2+}$) out of enterocytes, macrophages, and hepatocytes into circulation.

Hepcidin

A hepatic peptide hormone induced by inflammation and infection that binds ferroportin, causing its internalization and lysosomal degradation to inhibit systemic iron export.

Divalent Metal Transporter 1 (DMT1)

An intestinal apical membrane transport protein responsible for importing non-heme ferrous iron ($Fe^{2+}$) into enterocytes.

Duodenal Cytochrome B (DCYTB)

A ferrireductase enzyme located on the intestinal brush border that reduces dietary non-heme ferric iron ($Fe^{3+}$) to ferrous iron ($Fe^{2+}$) prior to uptake by DMT1.

Hephaestin (HEPH)

A membrane-bound ferroxidase that oxidizes exported ferrous iron ($Fe^{2+}$) into ferric iron ($Fe^{3+}$) so it can be loaded onto circulating transferrin.

Erythroferrone

A hormone produced by erythroblasts that inhibits hepcidin expression, thereby increasing iron mobilization and availability for hemoglobin synthesis.

Iron-Responsive Elements (IREs)

RNA regulatory sequences in mRNAs encoding iron-homeostasis proteins that bind Iron Regulatory Proteins (IRPs) under low-iron conditions to regulate mRNA stability or translation.

Hereditary Hemochromatosis

A genetic disorder resulting from defects in negative regulators of hepcidin, hepcidin itself, ferroportin, or TfR2, leading to unregulated dietary iron absorption and tissue-damaging iron overload.

Apoptosis

An active, physiological programmed cell death process in which individual cells shrink, bleb their membranes, and undergo phagocytosis without causing tissue damage or inflammation.

Necrosis

A passive, pathological cell death process triggered by cellular injury or disease, characterized by plasma membrane rupture, cellular swelling, content leakage, and surrounding tissue inflammation.

Scramblase

An enzyme activated during apoptosis that translocates phosphatidylserine from the inner to the outer plasma membrane leaflet to mark apoptotic bodies for phagocytic recognition.

ROCK1

A kinase that catalyzes cytoskeletal rearrangement during apoptosis, driving the formation of plasma membrane blebs and apoptotic bodies.

Apoptosome

A large, ATP-dependent multiprotein complex formed by cytochrome c, Apaf-1, and pro-caspase 9 that cleaves and activates pro-caspase 9 into active caspase 9 during intrinsic apoptosis.

Caspases

A family of cysteine proteases synthesized as inactive zymogens that serve as initiator or effector enzymes in programmed cell death cascades upon activation.

Death-Inducing Signaling Complex (DISC)

A multiprotein complex formed by ligand-bound cell-surface death receptors, adaptor molecules like FADD, and pro-caspases 8 or 10 that triggers extrinsic apoptotic signaling.

Bcl-2 Family

A family of proteins that regulate mitochondrial outer membrane permeability, comprising pro-survival members (Bcl-2, Bcl-xL) and pro-death members (Bax, Bak, Bid).

FADD (Fas-Associated Death Domain)

An adaptor protein containing death domains that links activated Fas death receptors to pro-caspases 8 or 10 to assemble the DISC during extrinsic apoptosis.

Interphase

The extended period of the cell cycle between nuclear divisions consisting of $G_1$, $S$, and $G_2$ phases, characterized by cell growth, organelle duplication, and DNA synthesis.

Restriction Point

A critical checkpoint in late $G_1$ phase past which a cell is committed to continuing through $S$ phase and completing division independent of external growth factor signals.

Cyclins

Regulatory cell cycle proteins whose intracellular concentrations fluctuate systematically throughout the cell cycle to bind and activate specific cyclin-dependent kinases.

Cyclin-Dependent Kinases (CDKs)

Protein kinases present at constant total levels that fluctuate in enzymatic activity depending on binding to regulatory cyclins, driving target phosphorylation and cell cycle transitions.

Retinoblastoma Protein (RB)

A key tumor suppressor protein that halts the cell cycle in $G_1$ phase by binding transcription factor E2F until it is hyperphosphorylated by cyclin D-CDK4/6 complexes.

p53

A critical tumor suppressor protein activated by DNA damage that transactivates p21 to cause cell cycle arrest in $G_1$ for DNA repair, or induces Bax to trigger apoptosis if damage is irreparable.

p21 (p21CIP1)

A CIP/KIP family cyclin-dependent kinase inhibitor (CKI) induced by p53 that inhibits CDK activity, halting the cell cycle to allow DNA repair.

Quiescence (G0 Phase)

A specialized, reversible resting state off the active cell cycle entered by non-dividing cells that maintain the capacity to re-enter $G_1$ phase under proper stimulation.

Senescence

A state of permanent cell cycle arrest entered by cells due to advancing age or unrepairable DNA damage, preventing further cell division.

Mitotic Spindle Poisons

Chemotherapeutic agents (such as vincristine, vinblastine, and Taxol) that bind tubulin, disrupt mitotic spindle microtubule dynamics, and arrest actively dividing cells in metaphase.

Antimetabolites

Anticancer drugs structurally similar to normal cellular metabolites (such as methotrexate and 5-fluorouracil) that inhibit nucleotide precursor synthesis and exert toxicity during $S$ phase.