Oxidative Stress and Alcohol Metabolism Flashcards
Does alcohol have low or high energy content ?
High energy content , it has a higher energy content than protein and carbohydrates but lower energy content than fats. -29KJ/g
Where is the majority of alcohol metabolised ?
Over 90% metabolised in the liver
What is the recommended units a week of alcohol recommended ?
14 units a week spread over 3 days for BOTH MEN AND WOMEN.
How many units of alcohol is in 8g of alcohol ?
One unit
If someone heavily drinks one night , why are they recommended to not drive the following morning or afternoon ?
- because the elimination rate alcohol is 7g per hour so there is a danger that there still could be alcohol in the body above the recommended limit
Outline the process of alcohol metabolism
ETHANOL IS CONVERTED INTO ACETALDEHYDE by alcohol dehydrogenase. This in turn converts NAD+ into NADH. 2. ACETALDEHYDE is then converted into acetate by aldehyde dehydrogenase. This in turn converts NAD+ into NADH. 3. Acetate is then conjugated to coenzyme A to form acetyl -coA which can then enter TCA cycle or utilised for fatty acid synthesis.
What metabolite is responsible for the ‘hangover’ effect ?
ACETALDEHYDE
Prolonged and excessive alcohol consumption can cause accumulation of ———- and a decrease in the ——- ratio
- accumulation of acetaldehyde - decreases in the NAD:NADH ratio
How can a decrease in the NAD+/NADH ratio be responsible cause a change in liver metabolism ?
1) a decrease in the NAD+/NADH ratio results in less NAD+ for the conversion of lactate to Pyruvate which results in lactate accumulation in blood which results in lactic acidosis. Kidneys ability to excrete Uric acid reduced which results in urate crystals accumulating in tissues producing gout. 2) inadequate NAD+ for glycerol metabolism which results in deficit in gluconeogensis which results in hypoglycaemia 3) inadequate NAD+ for fatty acid oxidation which results in increased synthesis of triacylglycerols which results in fatty liver
How can the increased acetyl-coA lead to fatty liver ?
- increased synthesis of fatty acids and ketone bodies which results in fatty liver
What drug is used to treat chronic alcohol dependence ?
Disulfiram
Explain how disulfiram works ?
It is an inhibitor of aldehyde dehydrogenase - once they drink alcohol , acetaldehyde will accumulate causing severe symptoms of hangover - patient associates drinking with being sick etc - classical conditioning
Define a free radical
An atom or molecules that contains one or more unpaired electrons. - free radicals are very reactive and tend to acquire electrons from other atoms , molecules or ions
What is oxidative stress
An imbalance between free radicals and antioxidants in your body
What is reactive oxygen species an umbrella term for ?
- free radicals - reactive nitrogen species
Is oxygen molecule a radical ?
Yes , it is a biracial it has two unpaired electrons in different orbitals
What are reactive oxygen species ?
Chemically reactive spices that contain oxygen - these include superoxides , singlet oxygen , hydroxyl radical
How is a superoxide formed ?
Produced by adding an electron to molecular oxygen - O2*-
How is hydrogen peroxide formed ?
Adding an electron and 2H+ to a superoxide - hydrogen peroxide is NOT a free radical - but can react with Fe2+ to produce free radicals
What is the most reactive and damaging free radical ?
Hydroxyl radical OH*
How is hydroxyl radical made ?
Additional of electron and H+ to hydrogen peroxide
What are reactive nitrogen species
A family of antimicrobial molecules derived from nitric oxide ( NO*) and superoxide (O2*-)
Superoxide can react with nitric oxide to produce …
Peroxynitrite ( ONOO-) - its not itself a free radical but it is a powerful oxidant that can damage cells
What are the two main types of reactive oxygen species damage of DNA?
1) ROS reacts with bases of D A which can lead to mispairing and mutation 2) ROS reacts with sugar of DNA which can cause strand break and mutation on repair
when deoxyguanosine undergoes reactive oxygen species damage on the base , what molecule is produced ?
8-oxo-dEoxygyanosine
What can 8-oxo-dG be a measurement for ?
As a measure the of oxidative damage
How can ROS damage proteins?
1) reacts with the protein backbone which causes protein fragmentation which leads to degradation of protein 2) ROS reacts with the protein side gain which results in modified amino acids which can lead to disulfide bonds forming , hydroxylated addicts , dimers or carbonyls which leads to change in protein structure leading to a loss of function or gain in function.
