alcohol metabolism and oxidative stress

Question 1

where is alcohol metabolised

Answer 1

in the liver and the rest is excreted via the urine and breath

Question 2

at what rate is alcohol metabolised

Answer 2

always metabolised at the same rate not dependant on how much has been consumed

Question 3

how many units per week can one drink

Answer 3

14 units. They must be spread out over the week

Question 4

describe alcohol metabolism

Answer 4

alcohol is catalysed to acetaldehyde by alcohol dehydrogenase and then this is catalysed to acetate by aldehyde dehydrogenase. acetate then enters TCA by conversion acetyl coA is used in fatty acid synthesis

Question 5

which is the component of alcohol metabolism which causes hungover symptoms and why

Answer 5

acetaldehyde because it is toxic

Question 6

types of liver damage caused by alcohol

Answer 6

alcoholic hepatitis, cirrhosis, fatty liver, gout, hypoglycaemia and lactic acidosis

Question 7

what causes fatty liver

Answer 7

excess of NADH and acetyl coA from the metabolism of alcohol leads to increased fatty acid synthesis. more triglycerols and more fat in liver.

Question 8

what causes gout

Answer 8

due to inadequate NAD+ conversion of lactate to pyruvate is reduced and therefore lactate builds up and the kidneys ability to excrete uric acid also reduces leading to rate crystals accumulating in the tissues causing gout

Question 9

what causes lactic acidosis

Answer 9

lack of NAD+ leads to less conversion of lactate to pyruvate in the liver and therefore it builds up causing lactic acidosis

Question 10

what causes hypoglycaemia in alcoholics

Answer 10

decreased NAD+ leads to less glycerol metabolism and therefore reduced gluconeogenesis which decreases glucose levels and hypoglycaemia

Question 11

what causes liver cirrhosis

Answer 11

due to death of hepatocytes due to abuse of alcohol fibroblasts lay down scar tissue reducing the functioning of the liver

Question 12

how does disulfram work

Answer 12

blocks the enzyme aldehyde dehydrogenase meaning more of acetaldehyde is present leading to a much worse hungover feeling when drinking

Question 13

what is oxidative stress

Answer 13

an imbalance f the cell defences and the cell damage(caused by RNS and ROS free radicals). this is a large cause of disease.

Question 14

what are RNS and how are they formed

Answer 14

reactive nitrogen spices. nitric oxide radical (causes some damage) will turn to a peroxynitrite on the addition of superoxide causing lots damage to cells even though it is not a free radical itself.

Question 15

what are ROS and where are they found

Answer 15

reactive oxygen species. oxygen is a biradical. when is gains an electron it becomes a superoxide radical. then on the addition of 2 H+ ions and an electron hydrogen peroxide is formed (not a radical). when another electron and H+ ion is added to this a hydroxyl radical is formed which is the most damaging free radical.

Question 16

types of ROS damage

Answer 16

DNA damage- reacts with base causing misfiring or sugar phosphate backbone causing strand break
Protein damage- reacts with side chain causing carbonyls, dimers disulphide bonds e.c.t. reacts with backbone causing fragmentation and protein degradation
lipid damage- lipid per oxidation a H is pinched and then a chain reaction of this occurs across bilayer causing it to be disrupted

Question 17

endogenous sources of biological oxidants

Answer 17

ETC- an electron escapes and reacts with o2 in the mitochondria and a superoxide is formed
nitric oxide synthase- synthesis of NO radical for signalling use.
NADPH oxidase- using NADPH for rapid releasing ofsuperoxide and h2o2 for destruction of invading bacteria

Question 18

exogenous sources of biological oxidants

Answer 18

radiation, UV/ dryas, drugs such as primaquine, toxins and pollutants

Question 19

how superoxide dismutase and catalase act as cellular defences

Answer 19

superoxide dismutase catalyses superoxide to hydrogen peroxide and then catalase catalyses hydrogen peroxide to oxygen and water

Question 20

how does glutathione act as a cellular defence

Answer 20

glutathione donates an electron to the ROS to prevent them taking electrons from proteins and DNA e.c.t. it does this by forming disulphide bonds to another GSH to form a GSSG (oxidised) and as this happens it relates an electron to donate to the free radical

Question 21

how is GSSG regenerated back to GSH

Answer 21

it uses NADPH to break the disulphide bond ad operate them.

Question 22

why is the pentose phosphate pathway needed for the regeneration of GSH

Answer 22

because it uses NADPH which is produced by this pathway. the rate limiting enzyme in the is glucose-6-phosphate dehydrogenase.

Question 23

what does the ratio of GSH to GSSG tell you

Answer 23

it can show you the oxidative stress levels. As in more GSSG means more oxidative stress.

Question 24

how vitamins act as cellular defence against ROS

Answer 24

vitimin E (lipid soluble and able to enter the cell) and vitamin C (water soluble) reduce free radicals by donating an H atom

Question 25

what is galactosaemia

Answer 25

deficiency in enzymes so therefore galactose joins other pathways. aldose reductase pathway producing galacitcol is up-regulated and NADPH is used up in this pathway. this results in compromised ROS defence and cateracts

Question 26

what is G6PDH deficiency

Answer 26

less of the enzyme G6PDH in the pentose phosphate pathway meaning reduced amounts of NADPH. This reduced ROS protection and results in lipid per oxidation and protein damage. This can cause Heinz bodies which the spleen removes because it detects the precipitated haemoglobin. = anaemia

Question 27

what happens when you overdose on paracetamol

Answer 27

usually products include glucuronide and sulphate but when you have an overdose produces NAPQI which has toxic effects

Question 28

what is the antidote to NAPQI and how does it work

Answer 28

the antidote is acetylcysteine which replenishes glutathione levels which metabolises NAPQI preventing liver damage.