Oxidative Stress And Alcohol Metabolism Part 2

Question 1

How do ROS damage lipids ?

Answer 1

• free radical ( OH*) extracts hydrogen atom from a polyunsaturated fatty acid in membrane lipid.
• lipid radical formed which can react with oxygen to form a lipid peroxyl radical
• this leads to a chain reaction as lipid peroxyl radical extracts hydrogen from nearby fatty acids
• this leads to hydrophobic environment of bilayer of membrane disrupted

Question 2

What are a few endogenous sources of biological oxidants ?

Answer 2

1) electron transport chain
2) nitric oxide synthases
3) NADPH oxidases

Question 3

What are a few exogenous biological oxidants ?

Answer 3

1) drugs for example the anti malarial drug primaquine
2) radiation ( UV light , x rays , cosmic rays)
3) Paraquat ( herbicide ) -
4) pollutants

Question 4

How is the electron transport chain a source of endogenous ROS ?

Answer 4

occasionally electrons can accidental escape chain and react with dissolved o2 to form superoxide

Question 5

How does nitric oxide synthase act as a source of endogenous NOS?

Answer 5

Nitric oxide synthase converts arginine into citrulline and nitric oxide ( NO*)

Question 6

What are the effects of nitric oxide ( NO*)

Answer 6

1) very toxic at high levels

2) can act as a signalling molecule - vasodilation, neurotransmission and S-nitrosylationa

Question 7

What are the three types of nitric oxide synthase ?

Answer 7

1) iNOS : ineucable nitric oxide synthase. Produces high NO concentrations in phagocytes for direct toxic effect
2) eNOS: endothelial nitric oxide synthase used for signalling
3) nNOS: neuronal nitric oxide sytnthase ( signalling )

Question 8

What is respiratory burst

Answer 8

Rapid release of reactive oxygen species

Question 9

Outline the mechanisms in respiratory burst that occur as part of the antimicrobial system

Answer 9

1) iNOS produces large amounts of NO* which combines with superoxide to make ONOO- ( peroxynitrite) which goes off to attack bacteria
2) superoxide gains 2H+ and e- to make H202 which can combine with CL- to make hypochlorite ( this is found in bleach) this is with the help of myeloperoxidase enzyme.

Question 10

CELLULAR DEFENSES FROM OXIDATIVE STRESS : superoxide dismutase and catalase

Answer 10

1) superoxide dismutase converts superoxide to H202 and oxygen .
2) catalase then converts H202 to water and oxygen

Question 11

HOW IS glutathione converted into their oxidised form and how does it protect against oxidative damage ?

Answer 11

• glutathione is a tripeptide synthesised by the body to protect against oxidative damage.
• the thiol group of CYS donates e- to ROS. GSH ( reduced form) then reacts with GSH to form disulphide ( GSSG)
• this is with the aid of the enzyme glutathione peroxidase (H2O2 into H20)
• glutathione peroxidase requires selenium

Question 12

How is the oxidised form of glutathione ( GSSG) converted into their reduced form ?

Answer 12

Reduced back to GSH by glutathione reductase which catalyses the transfer of electrons from NADPH to disulfide bond

• NADPH is from the pentose phosphate pathway.

Question 13

Cellular defences : give examples of free radical scavengers

Answer 13

1) vitamin E - lipid soluble,e antioxidant - important for protection against lipid peroxidation
2) vitamin C - water soluble antioxidant : important role in regenerating reduced form of vitamin E
3) uric acid , melatonin

Free radicals scavengers reduce free radical damage by donating hydrogen atom and its electron to free radicals in a non enzymatic reaction.

Question 14

What occurs when paracetamol is taken in large amounts ?

Answer 14

1) paracetamol enters a new pathway and is converted into NAPQI which leads to direct toxic effects For example liver peroxidation , damage to proteins and damage to DNA through oxidative damage

Question 15

How do you treat paracetamol overdose ?

Answer 15

Acetylcysteine treatment which increases levels of glutathione

Question 16

What are symptoms of G6PDH DEFICIENCY ?

Answer 16

1) anaemia ( dB concentration below normal range for age and gender , increased in breakdown of RBC or reduced production , increased number of recticulocytes in peripheral blood)
2) jaundice
- caused by an increase in bilirubin which is a yellow by - product of RBC breakdown produced from metabolism of the haem group of HB. normally excreted in bile and urine.