Session 1- Alcohol Metabolism+ Oxidative Stress+ Protein And Amino Acid Metabolism Flashcards
Describe the metabolism of alcohol.
Alcohol is metabolised in the liver.
Alcohol is converted into acetaldehyde via alcohol dehydrogenase
Acetaldehyde is converted into acetate via aldehyde dehydrogenase.
How the metabolism of alcohol can cause damage to the liver.
Over-consumption of alcohol can lead top sufficient accumulation of acetaldehyde in the liver which is toxic to cells.
- Decrease in NAD+/ NADH ratio
- Increased Acetylcholine-CoA
What are the toxic effects of acetaldehyde?
- Damaged liver cells gives leaky plasma membrane which result in loss on enzymes such as transaminases and gamma glutamic transpeptidase.
- Reduction in capacity to take up bilirubin leads to hyperbilirubinaemia
- Reduction in capacity to produce urea leads to hyperammonaemia+ increased levels of glutamine
- Reduced protein synthesis leads to decreased albumin, clotting factors and lipoproteins synthesis
- Low albumin produces oedema.
What are the effects of decreased NAD+/NADH ration on the liver?
- Inadequate NAD+ for fatty acid oxidation
- Increased synthesis of triacylglycerol
What are the effects of increased Acetyl- CoA on the liver?
- Increased synthesis of fatty acids and ketone bodies
- Increased synthesis of triacylglycerol
- Leads to fatty liver
Explain the mechanism of action of Disulfiram in the treatment of alcohol dependance
Disulfiram is an inhibitor of aldehyde dehydrogenase
When a person drinks alcohol, this will cause acetaldehyde to accumulate causing symptoms of a ‘hangover’
Describe the production of superoxide radicals by mitochondria
During oxidative phosphorylation about 0.1%-2% of electrons do not reach the end of the electron transport chain and they prematurely reduce oxygen to form superoxide radicals.
Discuss other Reactive oxygen species and reactive nitrogen species
Hydroxyl radical- most damaging because it can react with anything. Formed from hydrogen peroxide combining with a hydrogen ion and an electron
Nitric oxide- forms peroxynitrite which is highly reactive as it is capable of oxidising a variety of molecules
Outline cellular defences against reactive oxygen species
- Superoxide dismutase which converts superoxide into hydrogen peroxide.
- Catalase breaks down hydrogen peroxide into water and oxygen
- Glutathione- The sulfurhydryl group of the Cys residue donates an electron to ROS + reacts with another gsh to form a disulphides bridge
- Free radical scavengers, vitamin C and E, important antioxidant. Vitami E is lipid soluble and helps against lipid per oxidation and vitamin C is water soluble and helps in regenerating the reduced form of vitamin e
- Scavengers reduce damage by donating a H atom to ROS.
Explain the importance in NADPH and glutathione
There is a recycling system between NADPH and glutathione.
NADPH reduces oxidised glutathione to its reduced form, via the enzyme GSH reductase. The reduced glutathione is then available to be oxidised by reactive oxygen species, thus removing ROS
Explain the role of oxidative stress in disease states
The production of ROS is greater than the antioxidants.
Explain respiratory burst
Where neutrophils+ monocytes are stimulated by the immune system to rapidly release ROS in order to kill surround bacteria/fungal cells and uses the enzyme NADPH oxidase.
Genetic defect in NADPH OXIDASE, so less oxygen radicals formed which inhibits further reactions in the pathway such as the production of peroxynitritite and hypochlorites which therefore more susceptibility to bacteria as they are less likely to be killed because not enough ROS produced.
Galactosaemia and G6PDH
- We have either a defect in the enzymes UDP-epimerase, uridyl transferase or galactokinase
- Increased activity of aldose reductase so more NADPH is converted
- Glucose-6 phosphate deficiency, NADPH production is limited.
- Insufficient levels of NADPH will cause less Oxidised glutathione to go into the protective reduced form, leaving the cell susceptible to oxidative damage.
How does ROS damage DNA?
-ROS reacts with base: modified base can lead to mispairing and mutation
-ROS reacts with sugar: (ribose or deoxyribose)
Can cause strand break and mutation on repair
