Module C-Toxiodynamics

Module C-Toxiodynamics - Many molecules that are toxic in...

Info iconThis preview shows pages 1–2. Sign up to view the full content.

View Full Document Right Arrow Icon
Many molecules that are toxic in the cells are by being electrophilic Toxiodynamics Process in cells and tissues by which xenobiotics can exert a significant effect Many drugs that are toxic are by virtue of being electrophilic APAP when metabolized in liver to NAPQI- NAPQI causes hepatic damage b/c its electrophilic Electrophilic molecules : organic chemical compounds that have a deficiency in electrons in one of their functional groups. Overall they may be electrically neutral, or a positive charge. There must be just one functional group that is electron deficient in order to be electrophilic molecule. Will react with electron rich molecules, which are common in cells, many of which are macromolecules these area called neucleophiles All do carry a partial positive charge, making them electrophilic Will seek out moleucles that are electron rich- these are common in the body – many of these are macromolecules “Electrophilic attack” The way electrophiles work – so reactive that it takes less than second for the electrophile to migrate through cell and attack a molecule Two kinds of electrophilic molecules : hard – a lot of polarization of electric charges; preferentially react with nucleophiles that are correspondingly hard –the bases in DNA are hard and soft – have less polarized groups. W henever you have a protein, that protein is going to be a likely target by soft electrophiles. The products are called Adducts Methyl and ethyl are alkyl groups- (they are small, so they don’t cause much structural changes) these alkalization kinds of adducts often react with DNA change the genetic code of the particular gene, they give rise to codene lesions (code is miscoded ) this is known as informational changes Bulky adducts : they are big (BPDE forms a bulky adduct, so do ALFB1 - alter structure and genetic code and therefore are known as structural lesions ) - change structure and function significant distortion Cross-linking adducts: in this case there is 2 electrophlic groups on a single molecule going to react in such a way that one functional group attaches and 2nd attaches to a different molecule. And then the adduct is basically a bridge- connecting 2 molecules that were previously unrelated. Also known as - Interstrand cross-links where the centre strand and anti-strand are linked together – and that’s not supposed to happen Effect of charge polarization gradient in “hard” and “soft” electrophilic molecules Ethelyene (double C molecule): symmetricall, not electrophilic. Symmetrical charge distribution, nothing sticking out that’s going to react Formaldehyde quite reactive once it gets into airways; it’s a hard electrophile and that’s why its reactive, very small molecule; O2 is an
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 2
This is the end of the preview. Sign up to access the rest of the document.

Page1 / 15

Module C-Toxiodynamics - Many molecules that are toxic in...

This preview shows document pages 1 - 2. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online