76 Questions
What type of mutation occurs when a purine is substituted for another purine?
Transition
What is the main difference between toxicokinetically derived mechanisms and toxicodynamically derived mechanisms?
One alters the way chemicals are absorbed, while the other modifies target sites
At what levels can protection against toxic chemicals occur?
At the molecular, genetic, cellular, tissue, organ, and whole organism levels
What is the result of a point mutation that substitutes a pyrimidine for another pyrimidine?
A transition
Where did the earliest studies on tolerance and resistance mechanisms come from?
Insect/pesticide literature
What is the purpose of the mechanisms of resistance used by organisms?
To avoid the effects of toxic substances
What is the primary mechanism of toxicokinetically derived resistance?
Increased metabolic transformations of xenobiotics
What is the result of sequestration of contaminants within cellular organelles or binding to proteins?
Toxicants are unable to exert their toxic effects
What is an example of a storage site for organic xenobiotics?
Fat
What is the function of the GSH thiol group in cellular detoxification?
Performing a nucleophilic attack on the target electrophile
What is the mechanism of molecular repair of proteins involving thiol group oxidation?
Enzymatic reduction catalyzed by thioredoxin and glutaredoxin
What is the primary mechanism of toxicodynamically derived resistance?
Alterations in xenobiotic-receptor interactions
What is the function of molecular chaperons in protein repair?
To clamp down onto the exposed hydrophobic part and utilize ATP hydrolysis
What is the result of non-silent point mutations within structural genes?
Target site modification
What is the function of solute carrier proteins in elimination?
Mediating the vectorial transport of substrates into the cells
What is the purpose of ubiquination of proteins?
To target proteins for degradation in the proteasome
What is the role of glutathione peroxidase and glutathione reductase in lipid repair?
To repair peroxidized lipids
What is the level at which repair mechanisms can occur?
At the molecular, cell, or tissue levels
What is the result of increased metabolic transformations of xenobiotics?
Formation of less toxic or persistent forms
Why is mitochondrial DNA more prone to damage than nuclear DNA?
Because it lacks efficient repair mechanisms
What is the function of DNA photolyase in DNA repair?
To cleave adjacent pyrimidines dimerized by UV light
What is the role of biotransformation in the elimination of toxicants?
Enhancing the elimination of toxicants
What is the purpose of base excision repair in DNA?
To remove lesions that do not cause major distortion of the helix
What is the result of unrepaired double-strand breaks in DNA?
Apoptosis or check of cell-cycle progression
What is the likely function of the protein mentioned in the first sentence?
To repair broken DNA ends
What is the role of O6-methylguanine-DNA methyltransferase (MGMT) in cells?
To protect cells against the toxic effects of alkylating agents
What is the role of exonucleases or helicase activity in homologous recombination?
To produce a 3'-ended single-stranded tail
What is the major component of the nonhomologous end-joining repair complex?
DNA-dependent protein kinase
What is the purpose of chelating agents in the treatment of metal poisoning?
To form non-toxic complexes with metal ions
What is the characteristic of a good chelating agent?
Ability to reach sites of storage and form non-toxic complexes
What is the benefit of normal fluxes of proxidants in the cell?
They serve useful functions at the cellular and whole organism levels
What is the main factor in oxidative stress injury?
Loss of control of endogenous oxidative events
What is the percentage of O2 consumed by mammalian species that is delivered to mitochondria?
90%
What is the byproduct of the four-electron reduction of O2 to H2O by the respiratory chain?
ATP
What is the result of the incomplete reduction of O2 in mitochondria?
Formation of reactive oxygen species
What is the most reactive and short-lived biological radical?
Hydroxyl radical
What are the two main carotenoids that serve as provitaminA analogues and are effective antioxidants?
a- and P-carotene
What is ascorbate capable of rapidly scavenging?
All of the above
What is the result of ascorbate reacting with other cellular prooxidants?
Prolonging the lifetime of a-TOH in the lipid phase
What is the role of GSH-dependent reductase in ascorbate's antioxidant action?
Reducing dehydroascorbate back to ascorbate
What is the characteristic of certain cancer chemotherapeutic agents such as nitrogen mustards?
They are direct-acting electrophiles
What is the result of the conjugation of a biological reactive intermediate with GSH in bromobenzene metabolism?
Decrease in GSH concentration
What is the primary mechanism of APAP metabolism at normal dose levels?
Sulfation and glucuronidation
What is the role of the immune system in defending the body?
Distinguishing between self and non-self components
What is the result of APAP overdosage?
All of the above
What is the function of GSH in protecting against APAP toxicity?
Conjugating with NAPQI
What is the outcome of lipid peroxidation if termination reactions do not occur?
The process of lipid peroxidation will propagate, resulting in potentially high levels of oxidative stress.
What is the role of detoxification of endogenously produced H2O2?
To maintain redox homeostasis
What is the product of the dismutation reaction catalyzed by superoxide dismutases (SODs)?
H2O2
Where is manganese SOD (Mn-SOD) primarily located?
Mitochondria
What is the function of catalase?
To reduce H2O2 to H2O and O2
What is the role of glutathione peroxidase (GSH Px)?
To catalyze the reduction of organic peroxides
What is the function of glutathione reductase (GR)?
To reduce GSSG to GSH
What is the characteristic of small molecule antioxidants?
They can act by scavenging oxidants or chelating transition metal ions
What is the role of vitamin E in cells?
To scavenge a wide array of ROS
What is the role of ubiquinol Q10?
To act as a potent antioxidant in lipoproteins and other lipid membranes
What is the primary function of macrophages in the innate immune response?
To engulf and destroy infectious agents and foreign particles
What is the main difference between innate and acquired immune responses?
Innate responses are rapid but incomplete, while acquired responses are slower but more definitive
What type of cells are eosinophils particularly effective against?
Helminthic parasites
What is the role of cytokines in the immune system?
To regulate the activation, maturation, differentiation, and mobilization of immune cells
What is the primary function of neutrophils in the innate immune response?
To engulf and destroy infectious agents and foreign particles
What is the term for the process of enhancing phagocytosis by binding antibodies to molecules on the surface of microbes or other targets?
Opsonization
What is the primary function of dendritic cells in the immune system?
To present antigens to T cells
What is the term for the increased flow of blood to a site of inflammation, accompanied by increased permeability of capillaries?
Hyperemia
What is the primary function of the thymus in the immune system?
To differentiate T lymphocytes
What is the term for the localized aggregates of immune cells in the lung, gut, and skin?
BALT, GALT, SALT
What is the main function of natural killer cells in the innate response?
To lyse certain types of tumor cells and virally infected cells
What is the primary function of type I interferons in the innate response?
To inhibit viral replication and increase the lytic potential of NK cells
What is the role of pattern recognition receptors in the innate response?
To recognize features common to many pathogens and initiate an inflammatory response
What is the primary function of the complement system in the innate response?
To facilitate phagocytosis and pathogen membrane lysis
What is the role of macrophages in the acquired immune response?
To process and present antigens to T lymphocytes
What is the function of the T-cell antigen receptor (TCR)?
To recognize and bind to proteolytically processed short peptide fragments
What is the difference between Class I and Class II MHC molecules?
Class I MHC presents peptides derived from proteins produced within the cell, while Class II MHC presents peptides derived from proteins taken up by the cell
What is the role of protein-tyrosine phosphorylation in T-cell activation?
It is important in the initiation of cellular responses that follow TCR recognition of the MHC-antigen complex
What are the second messengers involved in the signaling pathways that lead to T-cell activation?
Inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG)
What is the role of cytokines in the initiation of inflammatory responses?
They are important in the initiation of inflammatory responses and help to mobilize immune cells to the site of injury
Test your understanding of DNA mutations, including transitions and transversions, and how organisms develop resistance to toxic chemicals. This quiz covers the basics of molecular biology and defense mechanisms.
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