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22 Cards in this Set

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What defines a monooxygenase rxn?
One in which one of the O of O2 is incorporated into the substrate and the other is reduced to H2O (often by NAD(P)H).
What do oxidases do (Griffith's def) P381
"A dump for two electrons". More formally, they act as an electron acceptor and are usually reduced to hydrogen peroxide.
What are two most dangerous species of oxygen?
Singlet oxygen and hydroxyl radical
What is the sequence of reductions of O2? (p384)
Oxygen to Superoxide to Hydrogen Peroxide to water and Hydroxyl Radical (-OH). The hydroxyl radical is further reduced to water.
Know the Haber-Weiss rxn on pg 388
Know the Haber-Weiss rxn on pg 388
What is the Fenton Rxn? p388
Creats Hydroxyl Radicals via:
Ferric Fe accepts an electron from O2- to make regular oxygen and Ferrous Fe. The Ferrous Fe then reacts with hydrogen peroxide to make Hydroxyl Radical (very bad), Ferric Fe, and Water.
Draw a dot-diagram of Hydroxide ion vs hydroxyl radical.
Ion has HO with 8e around O and a minus sign on upper right (that simply reacts with H+ to form water)
Radical has 7 electrons surrounding oxygen.
How many isoforms of NOS are there? Where is eNOS located?
3: neuronal nNOS, endothelial eNOS, and inducible iNOS. eNOS is found on vascular endothelial cells; not enough and people have hypertension. The inducible form is found in immune cells and causes enormous overproduction of nitric oxide - so much that it can cause severe hypotension
How does Nitroglycerin and drugs such as Viagra work? (p390)
Nitroglycerin provides source of NO to dilate cardiac arteries. Viagra inhibits Phosphodiesterase 5 - an enzyme that converts cGMP to GMP...cGMP is what causes muscle relaxation and vasodilation.

cGMP levels to increase, allowing blood vessels to dilate.
Re Peroxynitrite (ONOO-). What is the mechanism by which this is formed and how is it bad?
The body constantly has a bit of nitric oxide around to keep vasculature relaxed. However, when too much superoxide is around, it reacts with nitric oxide to form peroxynitrite. This is 1) toxic to cells 2) removes nitric oxide for normal vasodilation 3) removes nitric oxide required to limit platelet adhesion.
Despite a relatively large store of Fe (3.5-4.5 gm of Fe), how much do we lose and gain / day?
Just 1 mg/day both absorbed and released.
What controls the uptake of iron? Failure to do so causes?
The enterocyte. Hemochromatosis - in this case, the enterocyte does not limit the amount of Fe that's absorbed...there's too much in the system.
What is idiopathic hemochromatosis?
Pts absorb inappropriately lg amounts of iron through the gut. Over the years they develop a significant overload condition. Pathology includes liver damage, weakness, ROS damage to pancreas, etc.
How are pts with B-thalassemia major treated?
With blood transfusions and chelators to deal with the excess of Fe.
Describe how Transferrin works
Binds two Fe3+ atoms requiring bicarbonate to hold on to. Normally saturation is only at 30% - this is important first line of defense when there is a bleed - picks up free Fe quickly.
Describe how Ferritin works
"A ball of rust" It is found inside cells - 2nd lgst Ferric (Fe3+) store in the body that is contained by proteins. When converted to Fe2+, it leaves the ball of rust. Inflammation and superoxide formation can cause this conversion to Fe2+
How does Transferrin and Ferritin work together to store Fe? (p393)
Transferrin absorbs up to two Fe3+ atoms and bind to Transferrin receptor. The receptor/ferrotransferrin complex is absorbed into endosome. pH inside endosome drops to dissociate from transferrin and free Fe is stored in Ferritin. The Transferrin and its receptor return to surface.
What are dioxygenases? (p. 380)
Enzymes that split O2 and add both oxygen atoms to a substrate.
We need to know about monooxygenases, dioxygenase, and oxidase - briefly describe each
1. Mono = one oxygen from O2 is incorporated into substrate
2. Dioxy = both oxygens from O2 are incorportated
3. Oxidase = no oxygen to substrate but O2 acts as electron dump
What are the two most dangerous and two 2nd most dangerous oxygen species?
Singlet Oxygen and Hydroxyl radical; Peroxynitrite and hypochlorite
How is hydrogen peroxide typically formed?
By two-electron reduction of O2 or one electron reduction of superoxide.
What are the Reactive Oxygen Species
1. Singlet O2
2. Superoxide O2-
3. Hydrogen Peroxide
4. Hydroxyl Radical OH*
5. Nitric Oxide
6. Peroxynitrite