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level: STEP 2

Questions and Answers List

REACTION OF THE ULTIMATE TOXICANT WITH THE TARGET MOLECULE

level questions: STEP 2

QuestionAnswer
Usually, the ultimate toxicant reacts with a target molecule to cause toxicity. Subsequently, a series of secondary biochemical events occur, leading to __dysfunction or injury to target molecule itself, cell organelles, cells, tissues and organs, and even the whole organism
(ATTRIBUTES OF TARGET MOLECULES) 1 ALL ENDOGENOUS COMPOUNDS are potential targets for toxicants. The most prevalent and toxicologically relevant targets are __ 2 The FIRST TARGET for reactive metabolites is often the __ or the adjacent intracellular structures. 3 NOT ALL TARGETS FOR CHEMICALS contribute HARMFUL EFFECTS. True or False?1 nucleic acids (especially DNA), proteins, and membranes. 2 enzyme responsible for their production 3 True Covalent binding to proteins without adverse consequences (FORM OF DETOXIFICATION)
(ATTRIBUTES OF TARGET MOLECULES) 1 TO IDENTIFY A TARGET MOLECULE as being RESPONSIBLE FOR TOXICITY, it should be demonstrated that the ultimate toxicant: __. 1 REACTS WITH THE TARGET and adversely affects its function 2 Reaches an EFFECTIVE CONCENTRATION at the target site, 3 ALTERS THE TARGET in a way that is mechanistically related to the observed toxicity.
TYPE OF REACTIONS1) Noncovalent Binding 2) Covalent Binding 3) Hydrogen Abstraction 4) Electron Transfer
(TYPE OF REACTIONS) 1 __ involved in the interaction of toxicants with targets such as MEMBRANE RECEPTORS, INTRACELLULAR RECEPTORS, ION CHANNELS, & SOME ENZYMES. 2 usually is REVERSIBLE because of the comparatively LOW BONDING ENERGY.. (NONCOVALENT BONDING) 1 Apolar interactions or the formation of Hydrogen and Ionic bonds 2 Noncovalent binding
(TYPE OF REACTIONS) 1 irreversible. It permanently alters endogenous molecules. 2 COMMON WITH ELECTROPHILIC TOXICANTS such as nonionic and cationic electrophiles and radical cations. . 3 These TOXICANTS REACT WITH NUCLEOPHILIC ATOMS that are abundant in biological macromolecules, such as proteins and nucleic acids. Neutral free radicals such as HO• , •NO2 , and Cl3C• also can bind covalently to biomolecules.. (Covalent binding) 1 Covalent binding 2 Covalent adduct formation 3 ELECTROPHILIC TOXICANTS
(TYPE OF REACTIONS) 1 __ can READILY ABSTRACT H ATOMS from endogenous compounds, CONVERTING those compounds into RADICALS. 2 Radicals can also remove hydrogen from __ of free amino acids or from amino acid residues in proteins and convert them to __, forming crosslinks with DNA or other proteins.(Hydrogen Abstraction) 1 Neutral free radicals 2) CH2 groups, carbonyls
(TYPE OF REACTIONS) 1 Chemicals can exchange electrons to oxidize or reduce other molecules, leading to formation of harmful byproducts. For example, chemicals can oxidize Fe(II) in hemoglobin to Fe(III), producing __ 2 A few toxins ACT ENZYMATICALLY on specific target proteins. For example, __ BLOCKS THE FUNCTION OF ELONGATION FACTOR 2 in protein synthesis. 3 __ ACTIVATES A G PROTEIN through such a mechanism. 4 MOST ULTIMATE TOXICANTS act on endogenous molecules on the basis of their __(Electron Transfer) 1 methemoglobinemia 2 diphtheria toxin 3 cholera toxin 4 chemical reactivity.
EFFECTS OF TOXICANTS ON TARGET MOLECULES1) Dysfunction of target molecules 2) Destruction of Target Molecules 3) Neoantigen Formation
EFFECTS OF TOXICANTS ON TARGET MOLECULES (Dysfunction of target molecules) 1 Some toxicants activate __, mimicking endogenous ligands. 2 Chemicals inhibit the function of target molecules, by blocking __, inhibiting enzymes, and interfering with cytoskeleton dynamics. 3 When interaction with the toxicant changes the __ of the protein, protein function is IMPAIRED. 1 protein target molecules 2 neurotransmitter receptors or ion channels 3 shape or structure
EFFECTS OF TOXICANTS ON TARGET MOLECULES (Dysfunction of target molecules) 1 Many proteins contain critical moieties necessary for assembly of macromolecular complexes or catalytic activity. These molecules UNDERGO COVALENT AND/OR OXIDATIVE ALTERATION by xenobiotics, result in __ 2 Toxicants may obstruct DNA's ability to serve as a template. The covalent binding of chemicals to DNA causes __ during replication. 1 aberrant signal transduction and/or poor control of the cell's energy and metabolic homeostasis 2 Nucleotide mispairing
EFFECTS OF TOXICANTS ON TARGET MOLECULES (Destruction of Target Molecules) 1 In addition to adduct formation, TOXICANTS ALTER THE PRIMARY STRUCTURE of endogenous molecules by means of __ 2 imposes both STRUCTURAL & FUNCTIONAL CONSTRAINTS on the linked molecules.. 1 Crosslinking and Fragmentation. 2 Crosslinking
EFFECTS OF TOXICANTS ON TARGET MOLECULES (Neoantigen Formation) 1 Covalent binding of xenobiotics or their metabolites to protein may evoke an __ 2 These chemicals __ bind to proteins SPONTANEOUSLY. 3 Others may obtain reactivity by AUTOOXIDATION TO QUINONES like __ or by enzymatic biotransformation.. 1 immune response. 2 Dinitrochlorobenzene, Penicillin, and Nickel 3 Urushiols, the allergens in poison ivy
TOXICITY NOT INITIATED BY REACTION WITH TARGET MOLECULES 1 Some xenobiotics ALTER THE BIOLOGICAL MICROENVIRONMENT leading to a toxic response. Included here are:1) Chemicals that ALTER H+ CONCENTRATIONS in the aqueous biophase 2 Solvents and detergents that physicochemically ALTER THE LIPID PHASE of cell membranes and destroy transmembrane solute gradients, 3 Xenobiotics that cause harm merely by OCCUPYING A SITE.