MCP 7

Question 0

superoxide

Answer 0

primary ROS. O2 with an extra electron. it is a free radical as well as an oxidant (oxidizing agent). it participates in redox reactions where it is further reduced to hydrogen peroxide and hydroxyl radical, or the secondary ROS

Question 1

reactive oxygen species

Answer 1

chemically reactive molecular species formed upon incomplete reduction of oxygen. those containing an unpaired electron are called free radicals

Question 2

oxidative stress

Answer 2

caused by overoxidation of biological components of a cell

Question 3

where does most production of superoxide occur?

Answer 3

the mitochondria, as a byproduct of ATP synth.

Question 4

under what conditions are superoxide production increased?

Answer 4

1. high membrane potential: slower transfer of electrons leads to higher reduction levels of electron carried, increasing electron leak
2. High NADH/NAD+ ratio: causes overreduction of the electron transport chain
3. electron transport chain damage: damage can alter flow accuracy and increase leakage
4. xenobiotics: some xenobiotics interact with the mitochondrial electron transport chain and increase superoxide production rate. some block electron transport. involved in parkinsons disease
5. electron backflow in complex I: under some pathological conditions, over accumulated succinate during ischemia is rapidly oxidized by complex II, leading to over reduction of the Q site and drives back electrons through complex I

Question 5

NADPH oxidases

Answer 5

enzymes dedicated in superoxide production in cells that kill invading pathogensq

Question 6

Xanthine and monoamine oxidase

Answer 6

produce ROS as a metabolic byproduct. XO catalyzes purine catabolism. MAO catalyzes dopamine catabolism in neuronal cells

Question 7

fenton reaction

Answer 7

converts H2O2 to OH. transfers an electron to H2O2 from a free metal like Fe2. over accumulation of free iron causes oxidative stress and human diseases

Question 8

Hydroxyl radical formation through radiation

Answer 8

induces homolytic fission of the O-O bond in H2O2. production of ROS is key in how radiation kills cancer cells

Question 9

reactive nitrogen/oxygen species (RNOS)

Answer 9

nitric oxide, or NO is primary RNOS. generated by nitric oxide synthase, which metabolizes arginine to citrulline. NO can react with superoxide to form peroxynitrite, or ONOO-. this is very reactive, and can give rise to hyroxyl radical

Question 10

DNA damage from ROS

Answer 10

nucleic acid binds iron well, so DNA is a favored target of OH from fenton reactions. OH extracts electrons from sugar or base moieties, resulting in DNA radicals which produce a large spectrum of lesions.

Question 11

formation of 8-hydroxy-2’-deoxyguanosine

Answer 11

results from guanosine oxidation. frequently used as an indicator for an extent of DNA damage in a cell. can mispair with deoxyadenosine, leading to G to T transversion

Question 12

lipid peroxidation in ROS damage

Answer 12

OH is highly active in mediating lipid oxidation. PUFAs are highly susceptible to peroxidation, as the hydrogens close to the double bonds are highly reactive and prone to losing e- to OH. can initiate a free radical chain reaction in the membrane causing membrane damage

Question 13

biomarkers for lipid peroxidation

Answer 13

malondialdehyde and 4-hydroxy-2E-nonenal

Question 14

protein carbonylation in ROS damage

Answer 14

hydroxyl radicals can directly oxidize amino acid side chains, causing protein damage. they mediate protein carbonylation, a process defined by addition of reactive carbonyl functional groups on proteins. most reactive are reactive aldehydes from lipid peroxidation such as 4-hydroxy-2E-nonenal. carbonylation affects activity of target proteins or causes them to become degraded by protein quality control machines

Question 15

destruction of superoxide

Answer 15

Superoxide dismutase (SOD) converts two molecules of superoxide into one molecule of O2 and one molecule of H2O2. SOD is compartmentalized in the cell. cytosolic SOD contains Cu and Zn. mitochondrial DOS contains Mn

Question 16

amyotrophic lateral sclerosis (ALS)

Answer 16

mutations in Sod1, or the one in the cytosol with Cu and Zn.

Question 17

glutathione peroxidase

Answer 17

contains selenium. converts H2O2 to water, consuming 2 molecules of reduced glutathione. glutathione contains an electron rich functional group. reduced glutathione is regenerated by glutathione reductase, which needs NADPH. NADPH is regenerated by glucose 6 phosphate dehydrogenase. deficiency in this can cause oxidative stress

Question 18

peroxiredoxin pathway

Answer 18

uses sulfhydryl containing protein peroxiredoxin. important for detox of H2O2 in mitochon and erythrocytes. peroxiredoxin reacts with H2O2 to form water concomitant with the production of oxidized peroxiredoxin with a disulfide bond. this is then reduced by thioredoxin, to give oxidized thioredoxin. this is reduced through thioredoxin reductase. NADPH is used

Question 19

catalase

Answer 19

heme containing enzyme that catalyzes the decomposition of hydrogen peroxide to water and oxygen. uses one H2O2 to reduce another essentially. usually located in the peroxisome

Question 20

coenzyme Q (ubiquinone)

Answer 20

found in other membranes and lipoproteins. reduced form of CoQ10 has anti-oxidative function. it is now used as a dietary supplement and for antioxidant therapy. believed to scavenge RO2 radicals and inhibit lipid peroxidation

Question 21

glutathione

Answer 21

GSH keeps sulfhydryls of proteins reduced and maintains their biological activity. highly abundant in the cytosol, nuclei, and mitochon and is the major soluble antioxidant in these compartments. cells try to keep a high ratio of GSH to GSSG.

Question 22

dietary antioxidants

Answer 22

Vitamins E and C. plant phenols. flavonoids

Question 23

redox signaling

Answer 23

ROS/RNOS needed for this. regulates cell growth, differentiation and apoptosis. regulates cell processes such as innate immunity, anti-cancer, body weight control, and wound healing

Question 24

what is used as redox state indicators?

Answer 24

GSH/GSGG and TRX(SH)2/TRXS2 ratios

Question 25

second messengers

Answer 25

ROS such as H2O2 can be considered these, as increased H2O2 production can lead to the oxidation of specific reactive cysteine residues within regulatory proteins, modulating their function

Question 26

respiratory burst

Answer 26

phagocytes undergo this upon activation by ingestion of microorganisms. this robust oxygen consumption is related to a superoxide generating enzyme, phagocytic NADPH oxidase. ROS derived from this kill microbial pathogens, and participate as redox signaling molecules

Question 27

problem with antioxidants in cancer patients

Answer 27

antioxidants can protect healthy people from cancer but promote the growth of pre-initiated tumor cells

Question 28

ROS in food intake and weight control

Answer 28

ROS production is increased in the POMC and AgRP in response to nutritional cues. ROS act as a signal for activating POMC neurons to release anorexigenic hormones and decreasing AgRP’s activity in secreting orexigenic hormones, reducing food intake