Oxidative Stress And Alcohol Metabolism Flashcards
(23 cards)
What % of alcohol is metabolised by liver and what % is excreted in breath and urine?
90% in liver, 10% in breath and liver
What is recommendations for alcohol consumption?
14 units per week spread over at least 3 days
how many g of alcohol in a unit and how many g eliminated per hour?
8 g in one unit, 7g excreted per hour
How is ethanol converted to acetate for krebs cycle or fatty acid synthesis?
ethanol oxidised by alcohol dehydrogenase and NAD to acetaldehyde
acetaldehyde oxidised to acetate by aldehyde dehydrogenase
What substance causes hangover symptoms ?
build up of acetaldehyde
Name an inhibitor of aldehyde dehydrogenase and its use
disulfiram
treats alcohol dependance by making hangover less severe
How does alcohol cause fatty liver disease?
- increased acetyl coA
- increased synthesis of fatty acid and ketone bodies
- acetaldehyde build up toxic to hepatocytes so some may die/ loose function
- this means lipoproteins cannot be synthesised
- liver is main centre of lipogenesis and less lipoproteins means less removal and so lipid accumulates leading to fatty liver
How does the decrease in NAD+ from alcohol metabolism lead to lactic aciosis and gout?
- Not enough NAD+ for lactate conversion to pyruvate
- Lactate accumulates in blood (leads to lactic acidosis)
- Kidneys ability to excrete uric acid crystals reduced
- urate crystals accumulate in tissues (leads to gout)
How does the decrease in NAD from alcohol metabolism lead to hypoglycaemia?
- Not enough NAD+ for glycerol (from triglycerides) metabolism
- Deficit in gluconeogenesis as glycerol needed as intermediate to get around irreversible steps
- less gluconeogenesis means less glucose production so hypoglycaemia
What reactive nitrogen species (nitrogen free radicals) are there?
nitric oxide (NO+•), peroxynitrate (ONOO-)- not free radical but powerful oxidising agent
How can ROS (reactive oxygen species) damage proteins?
- damage backbone and lead to fragmentation
- change or modifiy side chains to change amino acids
- disulphide bond formation when takes electrons away from cystenines
How can ROS damage DNA?
- react with base and cause mispairing and mutation
- reacts with sugar nucleotides to cause strand break and mutation on repair
What do ROS produce that can be measured in a cell as an indicator of oxidative damage?
8-oxo-dG
State where and how free radicals can form from endogenous sources?
- ETC- electrons escape and react with O2 to form superoxide
- Nitiric oxide synthase- creates nitric oxide which is used normally for vasodilation and neurotransmission but toxic at high levels
- NADHP oxidase/ respiratory burst- H2O2 and superoxides, as well as ONOO- and NO are released to kill bacteria
- Peroxidases
- Monoamine oxidase
State some exogenous sources of free radicals
- radiation
- pollutants
- drugs (primaquine- antimalarial)
- toxins (herbicides)
How does superoxide dismutase work?
converts superoxide in to H202 and O2
How does catalase work?
converts H202 to water and O2 (important in WBCs protection against respiratory burst)
How does glutathione (GSH) work and what is it?
a tripeptide synthesised by body .
Thiol group of cys donates e- to radical, then reacts with another GSH, forming a disulphide bond and becoming GSSG with enzyme glutathione peroxidase and selenium cofactor. GSSG is converted back to GSH by glutathione reductase and NADPH
State free radical scavengers that are non enzymatic
- Vit E, Vit C, flavenoids, uric acid, melatonin, carotenoids
What happens to paracetamol at normal doses?
- converted to glucuronide and sulphate (safely excreted)
What happens to paracetamol at over doses?
converted to NAPQI which causes oxidative damage to liver cells, damage to protein and DNA –> liver failure
How is paraectamol overdose treated?
Acetyl cysteine, this replenished glutathione levels so protects from oxidative damage
Which enzyme is important in producing the respiratory burst to fight infection?
NADPH oxidase
