Alcohol metabolism and oxidative stress Flashcards
Why does alcohol have a high energy content?
Alcohol contains a lot of fat
Where is alcohol metabolised within the body?
Mainly by the liver (90%), remainder excreted in ruin and breath.
How is alcohol generally metabolised in the body?
Alcohol is oxidised to form acetaldehyde by alcohol dehydrogenase and then this is converted to acetate by aldehyde dehydrogenase, acetate is converted to acetyl-CoA and used in TCANfor fatty acid synthesis.
What other ways can the body metabolise alcohol?
Small amounts can be oxidised by cytochrome p450 2E1 enzyme or by catalase in the brain.
What is the recommended limit for alcohol consumption?
14 units/week spread over at least 3 days for both men and women
How does prolonged and excessive alcohol consumption cause liver damage?
Leads to acetaldehyde accumulation which causes liver damage. Excess NADH and acetyl-CoA disrupt liver metabolism and lead to things like fatty liver, alcohol hepatitis and alcoholic cirrhosis.
Draw the metabolic responses to alcohol consumption.
Decrease in NAD+/NADH ratio: inadequate NAD+ leads to less conversion of lactate to pyruvate, therefore get lactic acidois and hypoglycaemia (less gluconeogenesis) and affects kidneys ability to excrete Uric acid (gout). Low NAD+ for glycerol metabolism, and fatty oxidation.
Increased acetyl Co-A:
Increased synthesis of fatty acids and ketone bodies, increased TAGs, therefore get fatty liver.
What is the treatment for alcohol dependence and how does it work?
Disulfiram, blocks aldehyde dehydrogenase, acetaldehyde will accumulate causing the symptoms of a hangover.
What do reactive oxygen species and reactive nitrogen species do to cells?
Damage nucleicnacids, proteins and lipids.
Name some diseases caused by oxidative stress.
CVDs, COPD, cancer, MS and RA, etc.
What is a free radical?
An atom or molecule that contains one or more unpaired electron and is capable of independent existence, usually are very reactive and tend to acquire electrons from other atoms, molecule or ions, usually begins a chain of reactions therefore damage is cumulative.
Name some damaging ROSs and RNS
Superoxide O2- and hydroxyl radical OH.
Nitric oxide NO. and peroxynitrite ONOO-.
How does ROS damage DNA.
Can react with bases to modify leading to mispairomg and mutation, can react with sugar (ribose and deoxyribose) to cause strand break and mutation on repair.
How does ROS damage protein?
Backbone:
Fragmentation and protein degradation.
Sidechain:modifies AAs e.g. carbonyls, disulphide bond, dimers, this changes protein structure which leads to either gain of function or loss and function and thereby protein degradation.
Why are disulphide bonds so important in protein structure and how can ROS affect this function?
Strong bonds that play an important role in folding and stability, formed between thiol groups of cysteine residues, ROS can take electrons from cysteines and cause misfolding, crosslinking and disruption of function.
