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level: STEP 3 B.

Questions and Answers List

B. IMPAIRMENT OF INTERNAL CELLULAR MAINTENANCE: MECHANISM OF

level questions: STEP 3 B.

QuestionAnswer
(Depletion of ATP) for survival, all cells must SYNTHESIZE endogenous molecules, ASSEMBLE macromolecular complexes, membranes, and cell organelles, MAINTAIN the intracellular environment, and PRODUCE ENERGY for operation. Agents that disrupt these functions jeopardize survival. There are THREE CRITICAL BIOCHEMICAL DISORDERS that chemicals inflicting cell death may initiate:__1 ATP depletion, 2 Sustained rise in intracellular Ca2+ 3 Overproduction of ROS and RNS ASO
(Depletion of ATP) plays a central role in cellular maintenance both as a chemical for biosynthesis and as the MAJOR SOURCE OF ENERGY. utilized in numerous biosynthetic reactions, and is INCORPORATED INTO COFACTORS as well as NUCLEIC ACIDS It is required for MUSCLE CONTRACTION and polymerization of the cytoskeleton, fueling cellular MOTILITY, CELL DIVISION, VESICULAR TRANSPORT, & MAINTENANCE OF CELL MORPHOLOGY.ATP
(Sustained Rise of Intracellular Ca2+) 1 ATP drives __ that maintain conditions essential for various cell functions 2 Electron transport chain at three sites: 3 Impairment of __ is detrimental to cells because failure of ADP rephosphorylation results in the ACCUMULATION OF ADP and its breakdown products, as well as DEPLETION OF ATP.. 1 Ion transporters (e.g., Na+ ,K+ ATPase) 2) 1 βOX = betaoxidation of fatty acids 2 Pi = inorganic phosphate 3 ANT = adenine nucleotide translocator 4 ATP SYN = ATP synthase (FoF1ATPase). 3 oxidative phosphorylation
(Sustained Rise of Intracellular Ca2+) 1 are HIGHLY REGULATED and maintained by the impermeability of the plasma membrane to Ca2+ and by transport mechanisms that remove Ca2+ from the cytoplasm. 2 ACTIVELY PUMPED FROM THE CYTOSOL across the plasma membrane and is sequestered in the endoplasmic reticulum and mitochondria.1 Intracellular Ca2+ levels 2) Ca2+
(Sustained Rise of Intracellular Ca2+) 1 Toxicants induce elevation of cytoplasmic Ca2+ levels by __ 2 causes Ca2+ to move down its concentration gradient from extracellular fluid to the cytoplasm. 3 Toxicants also may increase cytosolic Ca2+ inducing its __ from the mitochondria or the endoplasmic reticulum.1) promoting Ca2+ influx & inhibiting Ca2+ efflux from the cytoplasm. (let Ca2+ enter but not let it leave) 2 Opening of the ligand or voltagegated Ca2+ channels or damage to the plasma membrane 3 leakage
(Sustained Rise of Intracellular Ca2+) Sustained elevation of intracellular Ca2+ is harmful because it can result in:1 DEPLETION OF ENERGY reserves by inhibiting the ATPase used in oxidative phosphorylation, 2 DYSFUNCTION of microfilaments 3 ACTIVATION OF HYDROLYTIC ENZYMES 4 Generation of ROS and RNS
(Overproduction of ROS and RNS) 1 A number of xenobiotics can DIRECTLY GENERATE ROS and RNS, such as __ 2 Overproduction of ROS and RNS can be secondary to intracellular __ 3 Ca2+ helps generate ROS and/or RNS by activating __ in the citric acid cycle leading to increased activity in the electron transport chain and increased formation of O2 • and HOOH, and by activating nitric oxide synthase, which leads to formation of ONOO. 1 Redox cyclers and Transition metals 2 hypercalcemia 3 dehydrogenases