Study Guides (248,229)
Canada (121,419)
Health (181)
HLTH 340 (27)

Topic 15.docx
Premium

4 Pages
78 Views
Unlock Document

Department
Health
Course
HLTH 340
Professor
Steve Mc Coll
Semester
Fall

Description
Topic 15: Toxicodynamic Mechanisms - Free-Radical Toxicity Part II Sources of free radicals and oxidative stress  Again, what are some endogenous and exogenous sources of free radicals? Expound where necessary. o exogenous radicals  environmental oxidants (O3, NO2)  metabolic activation of xenobiotics  ionizing radiation  phagocytosis and inflammatory immune processes  free radical sensitizers -- i.e. free radical producers o endogenous radicals: many of these are generated within the cell through 1- electron transfer, which is when electrons enter biological reactions which they are not supposed to enter, and a single electron gets transferred  For example this can happen in:  Mitochondria: ET chain for oxidative phosphorylation (ATP production)  microsomes (smooth E.R.): ET chain for oxidative P450 reactions  Lysosomes: oxidative burst in phagocytosis (‘killing action’)  cell membrane: synthesis of inflammatory mediators (e.g. prostaglandin synthetases) Production of superoxide radical by 1-electron rxn at complex II in the mitochondrial ET chain  So let's look into an example of how an accidental one-electron transfer can happen. Give a BRIEF overview of the ET (electron transfer) chain, and explain how an accidental one-electron transfer can occur. o Well recall that the electron chain is just the process of passing electrons to different complexes which want those electrons more and more -- and so as we pass the electron to something that wants it badly, it goes to a lower energy state and we can use the released energy to pump protons across o Sometimes we use shuttles to move the electrons from one complex to another:  Cytochrome C is the shuttle from 3 to 4  Coenzyme-Q is the shuttle between 1 and 3 o The point is that Co-Q is unfortunately accident prone/sloppy  Sometimes (1% or less), it will accidentally create a ONE-electron transfer (YIKES!) -- this gives the opportunity to have a superoxide, which you recall is O 2 o And thus we say that this is the leaky part of electron transfer Oxygen toxicity  What is the big picture here? What are the two types of oxygen toxicity we are discussing? o Oxygen toxicity is the idea that having too much OXYGEN can be toxic -- i.e. damaging to the body o The two types of oxygen toxicity we will explore are:  Pro-oxidants (i.e. nitrite), and what they can cause with oxygen and heme  Oxygen toxicity from hyperbaric/100% oxygen  First explain what the deal is with oxygen and heme. o Well firstly, recall that the heme group on hemoglobin (Hb) molecule is supposed to carry oxygen around -- so it'll bind to oxygen, bring it somewhere, then let it go (normally to myoglobin, but that is a separate discussion) o The deal here though is that the oxygen will steal an electron from the heme and become a superoxide radical! Not good! o Thus the progression we see is reduced hemoglobin aka hemoglobin (Fe++) -> oxygenated hemoglobin aka oxyhemoglobin (Fe++ -- O2) -> oxidized hemoglobin aka methemoglobin (Fe+++) o And the thing is that high levels of the pro-oxidant nitrite will drive this reaction forward, and so it is dangerous  It results in methemoglobin anemia, which is not enough oxygen due to the formation of methemoglobin  Kids will turn blue/purplish =/  Explain what the deal is with 100% oxygen/hyperbaric oxygen. o The mechanism is simplistic:  Higher levels of oxygen result in the greater production of superoxide radicals  These guys in turn can damage the:  Lungs, leading to bronchopulmonary dysplasia  Retina, leading to retrolental fibroplasia o Notably, large doses of vitamin E can rapidly reduce retrolental fibroplasia and bronchopulmonary dysplasia because it neutralizes the superoxides  Explain the contextual issues surrounding this. o Often it is NECESSARY to give such high doses of oxygen: for example when a baby is premature  So we give it to them to save their lives, but it can cause tissue damage as a result P-450 production of ROS and radical metabolites (bioactivation of xeniobiotics)  What was the point of this slide?
More Less

Related notes for HLTH 340

Log In


OR

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


OR

By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.


Submit