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Index
»
TOXICOLOGY
»
Mechanism of Toxicity
»
STEP 4 A. & B.
level: STEP 4 A. & B.
Questions and Answers List
level questions: STEP 4 A. & B.
Question
Answer
The fourth step in the development of toxicity is __
Initiate repair.
A. MOLECULAR REPAIR 1 Damaged molecules may be repaired in different ways. Some chemical alterations, such as OXIDATION OF PROTEIN THIOLS & METHYLATION OF DNA, are simply __ 2 HYDROLYTIC REMOVAL of the molecule's DAMAGED UNIT and insertion of a newly synthesized unit often occur with __
. 1 reversed. 2 chemically Altered DNA and Peroxidized Lipids. In some instances, the damaged molecule is totally degraded and resynthesized.
A. MOLECULAR REPAIR (Repair of Proteins) 1 essential for the function of numerous proteins. 2 Oxidation of protein thiols can be reversed by ENZYMATIC REDUCTION that is catalyzed by __ 3 Once oxidized, the catalytic thiol groups in these proteins are recycled by __
. 1 Thiol groups 2 Thioredoxin and Glutaredoxin. 3 reduction with NADPH.
A. MOLECULAR REPAIR (Repair of Proteins) 1 occurs by means of electron transfer from cytochrome b5, which is then regenerated by a NADH dependent cytochrome b5 reductase. 2 are synthesized in large quantities in RESPONSE TO PROTEIN DENATURATION 3 Damaged proteins can either be __, following ubiquitination in proteasomes. 4 Proteins can be eliminated by __ in lysosomes.
. 1 Repair of oxidized hemoglobin (methemoglobin) 2 Molecular chaperones such as the heatshock proteins 3 refolded with the help of chaperone proteins or degraded 4 proteolysis
A. MOLECULAR REPAIR ( Repair of Lipids) 1 Peroxidized lipids are repaired by a complex process involving a series of reductants which are the __. 2 __is needed to recycle the reductants that are oxidized in the process
. 1 glutathione peroxidase, and glutathione reductase 2 NADPH
A. MOLECULAR REPAIR ( Repair of DNA) 1 Despite its high reactivity with electrophiles and free radicals, nuclear DNA is remarkably stable, in part because it is packaged in __ and because several repair mechanisms are available to correct alterations 2 Mitochondrial DNA, however, lacks __ and therefore is more prone to damage.
. 1 chromatin 2 histones and efficient repair mechanisms
Types of DNA Repair
1 Direct Repair 2 Excision Repair 3 Recombination (or Postreplication) Repair
A. MOLECULAR REPAIR DNA Repair (DIRECT REPAIR) 1 Certain covalent DNA modifications are directly reversed by enzymes such as __, which CLEAVES ADJACENT PYRIMIDINES DIMERIZED BY UV LIGHT. This chromophore-equipped enzyme FUNCTIONS ONLY in LIGHTEXPOSED CELLS. 2 Minor adducts, such as methyl groups, attached to the O6 position of guanine are removed by __
. 1 DNA photolyase 2 O6 alkylguanineDNAalkyltransferase
A. MOLECULAR REPAIR DNA Repair (EXCISION REPAIR) 1 Two mechanisms for removing damaged bases from DNA. 2 Lesions that do not cause major distortion of the helix are removed typically by __
. 1 Base excision and Nucleotide excision 2 base excision.
A. MOLECULAR REPAIR DNA Repair (Recombination Repair) 1 __ occurs when the excision of a bulky adduct or an intrastrand pyrimidine dimer fails to occur before DNA replication begins. 2 Replication results in two homologous (“sister”) yet __ 3 the sister duplex that originally contained the gap carries in its daughter strand a section originating from the parent strand of the intact sister, which in turn carries in its parent strand a section originating from the daughter strand of the damaged sister— a process of __
. 1 Recombinational repair 2 dissimilar DNA duplexes: - one has large post replication gap & intact duplex 3 sister chromatid exchange.
B. CELLULAR REPAIR: A STRATEGY IN PERIPHERAL NEURONS 1 Repair of damaged neurons is MINIMALLY APPLIED in overcoming cellular injuries because MATURE NEURONS have __ 2 In PERIPHERAL NEURONS w/ AXONAL DAMAGE, repair does occur and requires __
. 1 LOST the ability to multiply. 2 Macrophages and Schwann cells.
B. CELLULAR REPAIR: A STRATEGY IN PERIPHERAL NEURONS 1 remove debris by phagocytosis and PRODUCE CYTOKINES & GROWTH FACTORS 2 these cytokines and growth factors activate __ to proliferate and transdifferentiate into a growth-supporting mode.
. 1 Macrophages 2 Schwann cells
B. CELLULAR REPAIR: A STRATEGY IN PERIPHERAL NEURONS 1 In the MAMMALIAN CENTRAL NERVOUS SYSTEM, axonal regrowth is prevented by growth inhibitory __produced by the oligodendrocytes and by the scar produced by __ 2 Although damage to central neurons is IRREVERSIBLE, the large number of __ can partly compensate by taking over the functions of lost neurons.
1 glycoproteins & chondroitin sulfate proteoglycans, astrocytes. 2 reserve nerve cells
C. TISSUE REPAIR 1 In tissues with cells capable of multiplying, damage is reversed by __ of the injured cells and regeneration of the tissue by __
1 apoptosis or necrosis, proliferation
C. TISSUE REPAIR - Apoptosis: An Active Deletion of Damaged Cells 1 Apoptosis initiated by cell injury can be regarded as __ 2 A cell undergoing __ shrinks as its nuclear and cytoplasmic materials condense, and then it breaks into membrane-bound fragments (apoptotic bodies) that are phagocytosed without inflammation. 3 The value of apoptosis as a tissue repair strategy is markedly lessened in organs containing __, such as the neurons, cardiac muscle cells, and female germ cells.
. 1 tissue repair. 2 apoptosis 3 nonreplicating and nonreplaceable cells
C. TISSUE REPAIR - Proliferation: Regeneration of Tissue 1 __allow adjacent cells to ADHERE to one other 2 CONNECT neighboring cells internally by association of these proteins into gap junctions. 3 LINK cells to the extracellular matrix.
. 1 Cadherins 2 Connexins 3 Integrins
C. TISSUE REPAIR - Proliferation: Regeneration of Tissue Repair of injured tissues involves both __
. 1 regeneration of lost cells & the extracellular matrix 2 reintegration of the newly formed elements into tissues and organs.