Flashcards in Week 5 ROS Deck (30)
what are ROS?
free radicals that have a single unpaired electron
what is the structure of super-oxide?
ROS: O2*- (*=lone electron)
what is the structure of hydroxyl radical?
where are superoxides produced?
mitochondria (Complex I+III of ETC), cytosol (XO), Lysosomes
What is the "lifespan" of a superoxide? key enzyme?
relatively short and they dont diffuse through membranes. they are quickly converted to H2O2 by superoxide dismutase
where is SOD located?
cytoplasm and mitochondria
H2O2 distribution within the cell
diffuses readily throughout the cell (also produced by auto oxidation in mito, oxidases in peroxisome, and SOD of mito and cyto)
what is the fenton reaction?
a reaction catalyzed by Cu and Fe that converts H2O2 to hydroxyl radicals
how else (other than fenton) can hydroxyl radicals be produced?
radiation + H2O
what is the roles (4) of peroxisomes?
beta oxidation of branched and VLCFA, AA catabolism, synthesis of bile acids (liver) and synthesis of plasmolegens (found in lipid membranes of brain, heart, neutrophils)
what enzymes do peroxisomes contain? what are their roles?
catalase and peroxidase and other oxidative enzymes: break down AA and FA
what is a by-product of FA oxidation in peroxisomes?
what is the role of catalase located? 2
converts H2O2 to H2O. peroxisome and lysosome
NADPH oxidase: size, role, found?
5 enzyme complex found associated with the membrane of lysosomes within Phagocytes (macrophages, monocytes, neutrophils). catalyze the formation of superoxide and NADP from NADPH and O2
where does the superoxide produced by phagolysosomes reside?
within the phagolysosomes; essential for the degradation/lysis of engulfed material
what are the fates of superoxide within a lysosome? 3
1. converted to H2O2 via SOD
2. H2O2 can be converted to water via catalase
3. H2O2 can be converted to HOCl via myeloperoxidase
what is the role of HOCl within a phagolysosome
HOCl is toxic to bacteria
what is chronic ganulomatous disease (cause? symptoms?)
caused by more than 400 gene mutations in 1 of 5 NADPH oxidase enzymes. Symptoms include frequent life threatening bacterial and fungal infection due to a lack of HOCl production
what is the role of Xanthine oxidase? found?
produces H2O2 and superoxide within the cytoplasm of cells as by-products of uric acid synthesis
What is the treatment for gout?
XO inhibitors to decrease the amount of uric acid crystals in kidney and joints
what is oxidative stress?
imbalance of ROS; could be high ROS or low ROS
what are three macromolecular complications associated with high ROS
lipid peroxidation, protein fragmentation, DNA oxidation
what is the cause of lipid peroxidation
ROS produce chain rxn of lipid peroxide formation.
what is the issue with lipid peroxidation 4
structural changes in PM (increase permeability), crosslinks with DNA, direct toxicity, disrupt signaling
what is the cause of protein fragmentation? what does it result in 3
ROS attack Cys, Met, Pro, His, Arg of membrane and cystolic proteins. causes protein degradation, altered protein fxn and increase membrane permeability (cell swells)
what do ROS do to DNA, what does this result in? 3
cause base modifications, ss DNA breaks and cross-linking. results in DNA repair, cell death or cancer
what are pro-oxidants? what are some examples?
induce oxidative stress. Ex. Mg, Fe, Cu that catalyze the fenton rxn
how do antioxidants fxn?2
prevent the formation of ROS or compete with oxidizable substrates
what are some examples of preventative anti-oxidants
XO inhibitors, NADPH oxidase inhibitors, metal chelaters