alcohol metabolism and oxidative stress Flashcards
where is alcohol metabolised
in the liver and the rest is excreted via the urine and breath
at what rate is alcohol metabolised
always metabolised at the same rate not dependant on how much has been consumed
how many units per week can one drink
14 units. They must be spread out over the week
describe alcohol metabolism
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
which is the component of alcohol metabolism which causes hungover symptoms and why
acetaldehyde because it is toxic
types of liver damage caused by alcohol
alcoholic hepatitis, cirrhosis, fatty liver, gout, hypoglycaemia and lactic acidosis
what causes fatty liver
excess of NADH and acetyl coA from the metabolism of alcohol leads to increased fatty acid synthesis. more triglycerols and more fat in liver.
what causes gout
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
what causes lactic acidosis
lack of NAD+ leads to less conversion of lactate to pyruvate in the liver and therefore it builds up causing lactic acidosis
what causes hypoglycaemia in alcoholics
decreased NAD+ leads to less glycerol metabolism and therefore reduced gluconeogenesis which decreases glucose levels and hypoglycaemia
what causes liver cirrhosis
due to death of hepatocytes due to abuse of alcohol fibroblasts lay down scar tissue reducing the functioning of the liver
how does disulfram work
blocks the enzyme aldehyde dehydrogenase meaning more of acetaldehyde is present leading to a much worse hungover feeling when drinking
what is oxidative stress
an imbalance f the cell defences and the cell damage(caused by RNS and ROS free radicals). this is a large cause of disease.
what are RNS and how are they formed
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.
what are ROS and where are they found
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.
types of ROS damage
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
endogenous sources of biological oxidants
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
exogenous sources of biological oxidants
radiation, UV/ dryas, drugs such as primaquine, toxins and pollutants
how superoxide dismutase and catalase act as cellular defences
superoxide dismutase catalyses superoxide to hydrogen peroxide and then catalase catalyses hydrogen peroxide to oxygen and water
how does glutathione act as a cellular defence
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
how is GSSG regenerated back to GSH
it uses NADPH to break the disulphide bond ad operate them.
why is the pentose phosphate pathway needed for the regeneration of GSH
because it uses NADPH which is produced by this pathway. the rate limiting enzyme in the is glucose-6-phosphate dehydrogenase.
what does the ratio of GSH to GSSG tell you
it can show you the oxidative stress levels. As in more GSSG means more oxidative stress.
how vitamins act as cellular defence against ROS
vitimin E (lipid soluble and able to enter the cell) and vitamin C (water soluble) reduce free radicals by donating an H atom
what is galactosaemia
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
what is G6PDH deficiency
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
what happens when you overdose on paracetamol
usually products include glucuronide and sulphate but when you have an overdose produces NAPQI which has toxic effects
what is the antidote to NAPQI and how does it work
the antidote is acetylcysteine which replenishes glutathione levels which metabolises NAPQI preventing liver damage.
