Session 1- Alcohol Metabolism and Oxidative stress

Question 1

how is alcohol metabolism

Answer 1

oxidised by alcohol dehydrogenase to acetaldehyde the to acetate to aldehyde dehydrogenase. Acetate converted to acetyl-coA which is used in the TCA cycle it for fatty acid synthesis

Question 2

how much is a unit of alcohol

Answer 2

8g
half pint of beer
small glass of wine

Question 3

what causes hangover

Answer 3

acetaldehyde which uses up NAD+ it is toxic

Question 4

what causes liver damage

Answer 4

acetaldehyde toxicity normally kept to a minimum by aldehyde dehydrogenase (low Km for acetaldehyde)

prolonged and excessive alcohol consumption can cause sufficient acetaldehyde accumulation to cause liver damage

excess NADH and Acetyl-CoA lead to changes in liver metabolism

fatty liver, alcoholic hepatitis, alcohol cirrhosis

Question 5

metabolic response to chronic damage

Answer 5

lactic acidosis
urate crystals accumulate in tissues producing gout
hypoglycaemia
fatty liver

Question 6

How does disulfiram treat alcohol dependence

Answer 6

disulfram can be used as an adjunct in the treatment of chronic alcohol dependence

it is an inhibitor of aldehyde dehydrogenase

if patient drinks alcohol acetaldehyde will accumulate causing symptoms of a hangover

Question 7

what is a free radical

Answer 7

an atom or molecule that contains one or more unpaired electrons and is capable of independent

free radicals are very reactive and tend to acquire electrons from other atoms. molecules or ions

reaction of a radical with a molecule typically generates a second radical thereby propagating damage

Question 8

what are the reactive oxygen species

Answer 8

superoxide- produced by adding electron to molecular oxygen.

hydrogen peroxide- not a free radical but can react to produce free radicals readily diffusible

hydroxyl radical- most reactive and damaging free radical. Reacts with everything

Question 9

reactive nitrogen species

Answer 9

nitric oxide

nitric oxide can react with superoxide to produce peroxynitrite which isnt a free radical but can damage cells

Question 10

what are the two types of damage a ROS can do

Answer 10

reacts with base- modified base can lead to mispairing and mutation (amino acid)

reacts with sugar- can cause strand break and mutation on repair (deoxyribose or ribose)

Question 11

how do free radicals affect disulphide bonds

Answer 11

inappropriate disulphide bonds formation can occur if ROS takes electrons from cysteines causing misfolding, crosslinking and disruption of function

Question 12

ROS damage to lipids

Answer 12

free radical 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

chain reaction formed as lipid peroxyl radical extracts hydrogen from nearby fatty acid

hydrophobic environment of bilayer disrupted and membrane integrity fails

Question 13

endogenous sources of biological oxidants

Answer 13

electron transport chain
nitric oxide synthases
NADPH oxidases

Question 14

exogenous sources of biological oxidants

Answer 14

radiation

• cosmic rays
• UV rays
• X-rays

pollutants
drugs
toxins

Question 15

what is iNOS

Answer 15

inducible nitric oxide synthase. Produces high NO concentrations in phagocytes for direct toxic effect

Question 16

what is eNOS

Answer 16

endothelial nitric oxide synthase (signalling)

Question 17

what is nNOS

Answer 17

neuronal nitric oxide synthase (signalling)

Question 18

what is respiratory burst

Answer 18

rapid release of superoxide and H2O2 from phagocytic cells
ROS and peroxynitrite destroy invading bacteria
part of antimicrobial defence system

Question 19

what is chronic granulomatous disease

Answer 19

genetic defect in NADPH oxidase complex causes enhanced susceptibility to bacterial infections

• atypical infections
• Pneumonia
• abscesses
• impetigo
• cellulitis

Question 20

what is superoxide dismutase

Answer 20

converts superoxide to h2o2 and oxygen

primary defence because superoxide is strong initiator of chain reactions
3 isoenzymes

Question 21

what is catalase

Answer 21

converts h202 to water and oxygen
widespread enzyme. Important in immune cells to protect against oxidative burst
declining levels in hair follicles with age may explain grey hair

Question 22

how is glutathione a defence against oxidative stress

Answer 22

uses NADPH from the pentose phosphate pathway to help convert H2O2 into H2O while becoming oxidised and reduced itself. The oxidised form of glutathione is GSSG.

Question 23

what are free radical scavengers

Answer 23

reduce free radical damage by donating hydrogen atom and its electron to free radicals in a nonenzymatic reaction

• vitamin E
• vitamin C

Question 24

how is vitamin E a free radical scavenger

Answer 24

lipid soluble antioxidant

important for protection against lipid perioxidation

Question 25

how is vitamin C a free radical scavenger

Answer 25

water soluble antioxidant

important role in regenerating reduced form of Vit E

Question 26

G6PDH Deficiency

Answer 26

decreased G6DPH activity limits amount of NADPH
lower GSH means less protection against damage from oxidative stress
NADPH required for reduction of oxidised glutathione GSSG back to reduced glutathione

Question 27

metabolism of paracetamol

Answer 27

at safe dosage paracetamol can be safely metabolised by conjugation with glucuronide or sulphate

with high levels of paracetamol the toxic metabolite NAPQI accumulates

Question 28

how does NAPQI affect the cell

Answer 28

it has direct toxic effects
oxidative damage to liver cells
-lipid peroxidation
-damage to proteins
-damage to DNA 

glutathione prevents this

Question 29

what is used to trat damage by NAPQI

Answer 29

acetylcysteine treatment- antidote works by replenishing glutathione levels