Term
| what is the definition of a free radical? |
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Definition
| any chemical species that is capable of independent existence while in possession of one or more unpaired electrons in it's outer shell |
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Term
| is O2 more soluble than water in organic solvents? |
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Definition
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Term
| what are the 2 kinds of free radicals? |
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Definition
ROS, reactive oxygen species
RNS, reactive nitrogen species |
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Term
| how are free radicals formed? |
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Definition
| by gain or loss of one electron from the outer shell |
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Term
| how does an antioxidant affect a free radical? |
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Definition
| antioxidants "quench" free radicals by providing another electron to the outer shell |
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Term
| what is a superoxide anion? |
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Definition
| an O2 molecule which has gained another e-, it is a ROS and free radical |
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Term
| what is hydrogen peroxide? |
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Definition
| a superoxide anion which has gained another e- as well as 2 H+, it is a ROS but not a free radical |
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Term
| what is the hydroxyl radical? what do you get if you reduce it? |
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Definition
| the most reactive of the ROS's and free radicals. reducing OH* will produce water. |
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Term
| where do ROS's come from? |
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Definition
| the ETC, where O2 is reduced, (specifically in complex 4, which includes cytrochrome-C oxidase and flavin enzymes), perioxisomes, (specifically fatty acid oxidases) and other sources such as radiation/toxic chemicals, drugs, and pollution |
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Term
| what are some examples of reactive nitrogen species, RNSs? |
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Definition
| nitric oxide, peroxynitrite |
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Term
| what are some uses of NO, (nitric oxide), in the body? |
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Definition
| it can function in small concentrations as a NT, vasodilator. however in response to inflammatory/mitogenic stimuli it is produced in toxic concentrations as a defense against non-self pathogens. NO* is short lived |
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Term
| what does peroxynitrite, (ONOO-), do in the body? is it considered a free radical? |
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Definition
| peroxynitrite is implicated in many diseases, it can oxidize anything in the cell, damaging proteins, DNA, and lipids. it can form nitrotyrosine, which is a biomarker for peroxynitrite damage. it is particularly damaging to PUFAs and LDLs. it is not considered a free radical |
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Term
| what are the beneficial effects of free radicals in the body? |
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Definition
| in low concentration, free radicals can regulate the metabolism, help turnover biomolecules, and protect against microbial infection, (ex: NADPH oxidase reduces oxygen to create superoxide for protection against invading bacteria) |
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Term
| what are some causes of oxidative and nitrosative stress? |
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Definition
| normal metabolism, high pO2, chemicals/drugs, reperfusion, aging, radiation, and inflammation |
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Term
| what is the progression of ROS formation? |
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Definition
| O2 -> O2* -> H2O2 -> OH* -> H20 |
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Term
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Definition
| singlet oxygen is the common name used for the diamagnetic form of molecular oxygen (O2), which is less stable than the normal triplet oxygen. it can have ROS properties after being produced in the body in a reaction involving ozone and several biological molecules, (albumin, urica acid, vit C) |
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Term
| how does the body get rid of superoxides? is this a fast rxn? |
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Definition
| superoxide dismutase changes superoxide to hydrogen peroxide and O2. this is a fast rxn |
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Term
| how does the body get rid of hydrogen peroxide? |
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Definition
| catalase changes hydrogen peroxide into water and O2. glutathione peroxidase can also do this using selenium giving off just water |
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Term
| what is the spontaneous rxn that occurs with Fe and hydrogen peroxide? |
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Definition
| the fenton-fenton rxn, which will produce the hydroxyl radical |
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Term
| what is hypochlorous acid? how is it made? |
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Definition
| HOCl, an antimicrobial, (was used IV before PCN). myeloperoxidase makes water and Cl into HOCl in phagocytic cells |
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Term
| what are organic radicals? |
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Definition
| organic radicals are produced when OH- attacks RH, giving off R*. (this can happen to Cs in double bonds or RSH groups can become RS*). lipid peroxidation can also result in organic peroxide radicals, (RCOO-) |
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Term
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Definition
| via nitric oxide synthase, of which there are 3 isoenzymes, 2 are neuronal and endothelial are physiological, and 1 is inducible which produces NO as a RNS for cytotoxic effects |
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Term
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Definition
| an anion, (ONOO-) formed by NO* and O2*, (superoxide, which as an affinity for NO*), peroxynitrite is involved in nitration of tyrosine/often lipid peroxidation |
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Term
| what are some uses of free radicals in the body? |
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Definition
| cytochrome P-450, eicosnoid synthesis, ETC, lodothyronine systems, phagocytosis, ribonucleoside reduction, xanthine oxidase |
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Term
| how does free radical-mediated cellular injury occur? |
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Definition
| hydrogen peroxide can penetrate the lipid membrane via lipid peroxidation, creating holes that Ca, Na, and H2O can enter the cell through. similar damage can occur to the membranes of the organelles, leading to damage of the DNA, inactivation of enzymes |
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Term
| what are the 2 end products of lipid oxidation that are biological markers for PUFA oxidation, and thus membrane damage? what about damage caused by peroxynitrite? what are some initiating events? |
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Definition
| MDA, (malondialdehyde), and 4-HDA, (4-hydroxydialkenals). nitrityrosine is a marker for peroxynitration. rxn with another radical and UV radiation can both be initiating events. |
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Term
| what ROS and RNS molecules in particular are damage causing agents to biological molecules? what can happen after the initial rxn? |
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Definition
| OH* and ONOO- a chain rxn can occur where each radical produced creates another after it |
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Term
| how do ROS and RNS affect carbohydrates? |
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Definition
| they modify the structure and function of the CHOs by forming hydroxyl radical products |
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Term
| how do ROS and RNS affect proteins? |
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Definition
| they modify both the structure and function of proteins. the damage is often site specific, occuring at metal bindng sites. metal catalyzed protein oxidation results in addition of carbonyl groups or cross-linking of proteins |
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Term
| how do ROS and RNS affect individual nucleotide bases? |
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Definition
| ROS and RNS cause single-strand breaks and cross linking in nucleic acids |
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Term
| how is comparmentalization utilized in cells in protection against fre radicals? |
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Definition
| vit E is lipid soluble, and thus is found in the membrane, vit C is water soluble and thus found in the cytosol |
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Term
| what is superoxide dismutase? where is it found? what ROS does it convert? |
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Definition
| SOD is found everywhere in the body, it converts superoxide to hydogen peroxide |
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Term
| what metal does catalase contain? what ROS does it convert? |
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Definition
| iron. it converts hydrogen peroxide to water and O2 |
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Term
| what metal does glutathione peroxidase convert? what ROS does it convert? |
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Definition
| selenium. it converts hydrogen peroxide to water |
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Term
| what are metal binding proteins? |
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Definition
| transferrin, lactoferrin, ceruloplasmin, albumin |
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Term
| what happens to glutathione, (GSH), after it converts hydrogen peroxide to water? |
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Definition
| in the process, glutathione is converted to its oxidized form glutathione disulfide (GSSG) which is changed back to GSH via glutathione reductase |
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Term
| what do tocopherols, (vit E) do in terms of antioxidant behavior? was is one caveat concerning vit E and ASA? |
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Definition
| they scavenge free radicals, and disrupt chain propagation. vit E also can augment anticoagulants like ASA, causing uncontrollable bleeding. |
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Term
| what do ascorbates, (vit C) do in terms of antioxidant behavior? |
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Definition
| they are reducing agents, scavenging myeloperoxidase derived oxidants. it helps recycle vitamin E back to its active form, and because of it's water solubility, the vit C radical form can be washed away. vit C also helps with iron absorption |
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Term
| what role does carotene play in terms of antioxidation? |
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Definition
| reacts with singlet O2, (an ROS that plays a significant role in protecting LDL |
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Term
| what is selenium's role in antioxidation activity? |
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Definition
| selenium indirectly spares vit E from oxidative damage, (part of glutathione peroxidase) |
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Term
| how is NADPH important in terms of antioxidant activity? |
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Definition
| NADPH is necessary to defend against ROS esp in terms of RBCs, which are particularly at rish b/c they come in contact with O2 and do not have mitochondria |
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Term
| what are the 2 ways that NADPH helps convert metHb back to Hb? |
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Definition
| either metHb reductase uses NADPH to convert metHb to Hb directly or indirectly via dehydriascorbate reductase |
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Term
| how does a glucose-6-phosphate dehydrogenase deficiency lead to damage of the RBC membrane? |
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Definition
| without G6P dehydrogenase, NADPH will not be formed, and glutathione reductase which needs it to function will not be able to convert GSSG back to GSH, which will cause a build up of ROSs which can then damage the membrane |
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Term
| what are the two main results of lack of NADPH? |
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Definition
| metHb accumulating as Heinz bodies, and ROS accumulation threatening damage of the RBC membrane |
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Term
| what is the most common genetic enzyme deficiency? what does its incidence coincide with? |
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Definition
| G6PDH which is X-linked. its incidence coincides with that of malaria |
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Term
| what are the 2 compounds in fava beans that are toxic to some people with G6PDH deficiency? |
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Definition
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