Session 1- Alcohol Metabolism And Oxidative Stress Flashcards
What happens to the majority of alcohol (more than 90 percent?).
The majority of alcohol is metabolised by the liver, the alcohol is oxidised by alcohol dehydrogenase to acetaldehyde and then acetate by aldehyde dehydrogenase. The acetate is then converted to acetyl coA and used in either the TCA cycle or for fatty acid synthesis.
What is it which causes a hangover?
When alcohol is oxidised to aldehyde acetaldehyde then aldehyde acetaldehyde is a toxic metabolite, the accumulation causes a hangover.
What drug is involved in treating alcohol dependence and how does it work?
Disulfiram it works by inhibiting aldehyde dehydrogenase, therefore acetaldehyde levels build up and cause hangover symptoms- putting people off.
What are free radicals?
Atoms or molecules which contain one or more unpaired electrons and is capable of independent existence (normally electrons of atoms/molecules/ions associate in pairs). Free radicals are very reactive and tend to acquire electrons from other atoms, molecules or ions.
What are the two main types of damage to DNA caused by reactive oxygen species?
The reactive oxygen species reacts with a base- the modified base can lead to mispairing and hence mutation.
The reactive oxygen species can react with sugar (ribose/deoxyribose) which can cause strand break and then mutation on repair.
How can reactive oxygen species cause damage to proteins?
By either affecting the side chains and hence modifying amino acids leading to protein degradation/loss of function/gain of function and protein degradation. The other way is by reacting with the backbone and therefore causing fragmentation and hence protein degradation.
Can ROS cause disulphide bond formation?
Yes ROS can cause disulphide bonds to form unnecessarily if ROS takes electrons from cysteines causing misfolding, crosslinking and disruption of function.
How do reactive oxygen species cause damage to lipids?
Free radical extracts hydrogen atom from a polyunsaturated fatty acid in the membrane lipid, a lipid radical is formed which can react with oxygen to form a LIPID PEROXYL RADICAL, this is a chain reaction as this lipid peroxyl radical then extracts hydrogen from nearby fatty acids, the hydrophobic environment of the bilayer is disrupted and the membrane integrity fails.
What are the sources of biological oxidants?
The sources of biological oxidants are either endogenous or exogenous.
Endogenous:
- Electron transport chain, Nitric oxide syntheses or NADPH oxidised.
Exogenous:
Radiation (cosmic rays/UV light/ X-rays), pollutants, drugs and toxins.
How are ROS formed in the ETC?
Occasionally electrons accidentally escape the chain and react with dissolves oxygen to form superoxide, they are meant to pass through the ETC and reduce oxygen to form H2O.
How does nitric oxide synthase (NOS) work?
What are the 3 types?
Works by converting ARGININE to CITRULLIINE which then reacts with nitric oxide.
The 3 types are:
INOS: inductively nitric oxide synthase, this produces high NO concentrations in phagocytes for a direct toxic effect,
Enos: endothelial nitric oxide synthase (Signalling)
nNOS: neuronal nitric oxide synthase (signalling).
What is nitric oxide?
Nitric oxide has a toxic effect at high levels, it is a signalling molecule for vasodilation, neurotransmission and S-Nitrosylation.
What is respiratory burst?
It is a rapid release of superoxide and H2O2 from phagocytic cells, the ROS and peroxynitrite (RNS) destroy invading bacteria, this is part of antimicrobial defence system.
There are cellular defences to ROS/RNS, what are they?
Superoxide dismutase (SOD) this converts superoxide to H2O2 and oxygen, it is a primary defence because superoxide is a strong initiator of chain reactions. THEN Catalase converts H202 to water oxygen, it is a widespread enzyme and is important in immune cells to protect against the oxidative burst!
Glutathione is another cell defence how does this work?
Glutathione is a tripeptide synthesised by the body which protects against oxidative damage, what happens in the thick group of Cys donates electrons to the ROS (reactive oxygen species) the GSH then reacts with another GSH to form disulphide forming GSSG (oxidised form), the GSSG is reduced back to GSH by glutathione reductase which catalysts the transfer of electrons from NADPH to disulphide bonds, NADPH from pentode phosphate pathway is therefore essential for protection against free radical damage.