Study Set Content:
STEP 2:
REACTION OF THE ULTIMATE TOXICANT WITH THE TARGET MOLECULE
the most prevalent and toxicologically relevant targets are ()()()
Nucleic acid(especially DNA), proteins, and membranes
The first target for reactive metabolites:
enzyme or intracellular structures.
To conclusively identify a target molecule as being responsible for toxicity, it should be demonstrated that the ultimate toxicant can either: o() with target and adversely affects its function
Reacts
Reaches an () at the target site
effective concentration
Alters target in a way that is mechanistically related to observed
toxicity
Types of Reactions
Noncovalent Binding o Covalent Binding o Hydrogen Abstraction- Electron Transfer o Enzymatic Reactions
Effects of Toxicants on Target Molecules
o Dysfunction of Target Molecule o Destruction of Target Molecule o Neoantigen Formation
Some xenobiotics alter the biological microenvironment leading to a toxic response. Included here are: o (1) chemicals that alter () concentrations in the aqueous biophase o (2) ()() that physicochemically alter the lipid phase of cell membranes and destroy transmembrane solute gradients o (3) xenobiotics that cause harm merely by () a site or space.
H+ ions , solvents and detergents, occupying
STEP 3:
CELLULAR DYSFUNCTION AND RESULTANT TOXICITIES
STEP 4
REPAIR OR DYSREPAIR
have the ability to recognize if there is something wrong.
Cells
Molecular Repair
Proteins Lipids DNA
are directly reversed by enzymes
Direct Repair
removes damaged bases
Excision Repair
directly ligates broken strands without the need for a homologous template. It is more error prone than other types of DNA repair.
Nonhomologous End Joining
requires a template from a sister chromatid.
Recombinational Repair or postreplication
is the removal of damaged cell organelles may be viewed as a universal mechanism of cellular repair.
Autophagic
Regeneration of damaged axons – specific for neurons and made assistance with macrophages in
Schwann cells.
An active deletion of damaged cells
Apoptosis
