level: STEP 3 C. & D
Questions and Answers List
INTERPLAY BETWEEN THE PRIMARY METABOLIC DISORDERS SPELLS CELLULAR DISASTER & D. MITOCHONDRIAL PERMEABILITY TRANSITION (mpt) AND THE WORST OUTCOME: NECROSIS
level questions: STEP 3 C. & D
| Question | Answer |
|---|---|
| C. The primary derailments in cellular biochemistry discussed may interact and amplify each other in a number of ways: | 1. Depletion of cellular ATP reserves deprives the endoplasmic and plasma membrane Ca2+ pumps of fuel, causing elevation of Ca2+ in the cytoplasm. 2. Intracellular hypercalcemia facilitates formation of ROS and RNS, which oxidatively inactivates the Ca2+ pump, aggravating the hypercalcemia. 3. ROS and RNS can also drain the ATP reserves 3 ONOO can induce DNA singlestrand breaks, which activate poly(ADPribose) polymerase (PARP). |
| C. 1 __ a reversible inhibitor of CYTOCHROME OXIDASE 2 INACTIVATES GLYCERALDEHYDE 3PHOSPHATE DEHYDROGENASE and IMPAIRS GLYCOLYSIS 3 irreversibly INACTIVATES SEVERAL COMPONENTS OF THE ELECTRON TRANSPORT CHAIN, inhibiting cellular ATP SYNTHESIS. | 1 NO (Nitric oxide) 2 NO+ (nitrosonium cation, a product of •NO) 3 ONOO (Peroxynitrite) |
| D. 1 are all considered as CAUSATIVE FACTORS of an abrupt increase in the Mitochondrial Inner membrane Permeability (or mitochondrial permeability transition), termed MPT. | . 1 Mitochrondrial Ca2+ uptake, 2 Decreased mitochondrial membrane potential, 3 Generation of ROS and RNS, 4 Depletion of ATP 5 consequences of the Primary metabolic disorders |
| D. 1 (mitochondrial permeability transition) MPT is caused by (the process) | 1 opening of a proteinaceous pore (permeable to solutes of 1500 Da.) 2 opening permits free influx into the matrix space of protons (rapid and complete dissipation of the membrane potential, cessation of ATP synthesis, osmotic influx of water causing mitochondrial swelling) 3) Ca2+ accumulated in the matrix space effluxes through the pore, flooding the cytoplasm. 4 glycolysis may become compromised by the insufficient ATP supply to the glycolytic enzymes that require ATP |
| (ATP Availability Determines the form of Cell Death) 1 Many xenobiotics can cause both __ 2 Toxicants tend to induce __ at LOW EXPOSURE LEVELS or early after exposure at high levels 3 whereas they cause __ later at HIGH EXPOSURE LEVELS | . 1 apoptosis and necrosis. 2 apoptosis 3 necrosis |