LC 42 Dr. Basel

Question 1

ROS or reactive oxygen species

Answer 1

describe why oxygen is both necessary and dangerous to organic organisms

Question 2

Reactive oxygen specices

Answer 2

Highly reactive oxygen containing compounds

Question 3

oxygen is a very _____ molecule that can be made to be even more ______.

Answer 3

reactive

Question 4

The most basic reactive oxygen species is superoxide which is the _____ electron ______ of molecular oxygen

Answer 4

single, reduction

Question 5

ROS act as _____ _____ removing electrons from other atoms

Answer 5

strong oxidizers

Question 6

Metal center oxidation

Answer 6

important to enzyme function causes them to not work or work abnormally

Question 7

Sulfide oxidation

Answer 7

Was neutral now its very negative. Certain seniors can make sulfur sulfur bonds

Question 8

Nitrogen oxidatiation

Answer 8

result is a negative acid

Question 9

carbon oxidation

Answer 9

results in negative acid

Question 10

Radicals in the ETC

Answer 10

The ETC creates a highly regulated radical, Q, in its complex. It is normal for a SMALL amount of radical to be leaked. If the system is starved of oxygen and not reperfused carefully the system can run in reverse and leak super oxide radicals

Question 11

Four examples of sources of ROS and intensification

Answer 11

1) Phagocytic Respiratory burst
2) Fe2+ and the fenton reaction
3) NO synthase
4) Ionizing radiation

Question 12

Phagocytic respiratory burst

Answer 12

Ex. neutrophil and macrophages. NADP oxidase expressed by phagocytic cells to make super oxide, Superoxide dismutase turns that to peroxide, Myeloperoxidase turns that into hypochlorous acid (bleach) to kill engulfed bacteria

Question 13

Fe2+ and the fenton reaction

Answer 13

Free Fe2+ causes problems in the cell (finds reactive oxygen species and activates them to be even stronger) so we want as little free Fe2+ as possible

Question 14

NO synthase

Answer 14

uses arginine+3 NADPH –NO synthase–> nitric oxide+ super oxide–> ONOO –> NO2 and HO

Question 15

Immune system can make a lot of different reactive oxygen species. If it is over stimulated what can occur?

Answer 15

Inflammation which can be very oxidative with the abundance of reactive oxygen species

Question 16

Ionizing radition

Answer 16

• creates double stranded DNA breaks
• more likely to hit water before DNA
• when this happens it knocks an electron off and becomes a hydroxyl radical
• starts a radical chain reaction
• potential for a lot of damage

Question 17

ROS + DNA

Answer 17

• oxidized DNA
• cross-linked DNA
• DNA adducts

Question 18

ROS + phospholipid

Answer 18

• lipid peroxides

- lipid adducts

Question 19

ROS + proteins

Answer 19

• oxidized AA
• protein dimers
• protein adducts

Question 20

ROS reactions with DNA, phospholipids or proteins can all result in what?

Answer 20

• cell damage
• disease
• neoplasm
• aging
• cell death

Question 21

Small antioxidants

Answer 21

Vitamin C and Vitamin E

Question 22

Peptide antioxidant

Answer 22

glutathione

Question 23

protein antioxidant

Answer 23

reduced thioredoxin, has two reduced cystines that it uses to donate to peroxide so it turns into water. When we use up thioredoxin we use NADPH to replace electrons and then it is reduced by Thioredoxin (uses selenium) and now it is replenished

Question 24

enzymatic antioxidants

Answer 24

superoxide dismutase and catalase

Question 25

What is found in nearly every cell that prevents the build up of ROS through enzymatic neutralization?

Answer 25

Superoxide dismutase and catalase

Question 26

How are Superoxide dismutase and catalase used by bacteria?

Answer 26

they are overproduced to try to counter phagocyte use of ROS to kill them

Question 27

What does superoxide do?

Answer 27

It reacts two super oxides

Question 28

How does catalase work with superoxide dismutase?

Answer 28

it takes two times its products of H2O2 + O2 and turns them into water and oxygen

Question 29

What happens if catalase and superoxide dismutase were mutated?

Answer 29

the cells die, its really not good

Question 30

Peptide antioxidant

Answer 30

glutathione (GSH) - most important intracellular antioxidant

Question 31

How is GSH used as an antioxidant?

Answer 31

2 GSH electrons/protons donated to hydrogen peroxide and cross links the GS molecules and produces water. This is done through the enzyme, glutathione peroxide.

Question 32

GSH is made of what three AA?

Answer 32

glutamate, cysteine and glycine - has free SH group that reacts well with oxidants

Question 33

How is GSH recycled?

Answer 33

cross linked GS --> add 2 NADPH --glutathione reductase (selenium important) --> produces 2GSH to be used again

Question 34

What is important for recycling antioxidants?

Answer 34

selenium

Question 35

Function of Vitamin C as an antioxidant

Answer 35

Vit C has conjugated double bonds OH. Radical steals proton from Vit C and now the radical is stable stopping a potential radical chain reaction. Can regenerate by handing radical off to another Vit. C fully oxidizing it.

Question 36

Function of Vitamin E as an antioxidant

Answer 36

Vit. E bonds radical so it is now stable. The Vit. E can be regenerated by handing the radical off to a Vit. C

Question 37

Central/ peripheral receptors

Answer 37

central and peripheral receptors are systemic level sensors to regulate O2 in the body. Peripheral sensors are able to detect O2 concentrations through glomus cells

Question 38

HIF

Answer 38

Hypoxia -inducible factors sense low oxygen in individual cells and promote hypoxia response genes

Question 39

ASK1

Answer 39

ASK 1 is a MAPKKK that is activated during oxidative stress conditions and promotes hyperoxia response genes

Question 40

The body has 2 systemic level sensors tied to respiratory control - one for CNS, one for PNS. Where are each of these receptors located?

Answer 40

CNS - ventrolateral surface of the medulla | PNS - carotid and aortic bodies

Question 41

What is the function of CNS receptor?

Answer 41

- regulation through stimulating respiration - does not sense oxygen level - primarily sense CO2/pH level and stimulate respiration in response

Question 42

What is the function of PNS receptors?

Answer 42

- regulation through stimulating respiration | - responsive to pO2, pCO2 and pH --> directly O2 sensitive unlike CNS

Question 43

Glomus cell and O2 sensing

Answer 43

- K+ channel is open with normal O2 - this keeps Ca2+ channel closed - O2 is turned to carbon monoxide (signaling molecule for K+ channels) by heme oxygenase, this keeps K+ channel open - O2 can also stimulate NADPH oxidase to use NADPH to make O2 into superoxide which keep K+ open - normal metabolism also makes superoxide which keeps K+ open - low oxygen leads to AMP build up - this goes to AMP kinase which closes K+ channel and Ca2+ opens

Question 44

What happens when Ca2+ are opened?

Answer 44

cell is depolarizing, Ca2+ runs into cell and allows vesicles to release neurotransmitters to stimulate axon and send message to the brain

Question 45

Hypoxia inducible factors or HIF

Answer 45

When O2 is low - HIF are transcription factors that are induced during hypoxia to make hypoxia response genes that protect against low oxygen Normal O2 - HIP prolyl hydroxylase oxidizes HIF to mark it for degradation so its signal is not received

Question 46

Individual cells can respond to low O2 true or false?

Answer 46

true, using HIF

Question 47

Hyperoxia and ASK1/MAPK pathway

Answer 47

When O2 is high - Thioredoxin is shifted towards being oxidized. It acts as a signaling molecule in this form. It doesn't bind ASK1 allowing it to dimerize to become active (in MAPKKK pathway) and push the cell towards hyperoxia gene expression and pro-apoptotic. Under normal conditions reduced thioredoxin binds ASK1, keeping it in an inactive form