Alcohol Metabolism, alcohol liver disease and alcoholism Flashcards
What is haematemesis?
- vomiting blood
What is melaena?
- black tarry stool
- digested blood from upper GIT
What is 1 unit of alcohol equal to?
- 100mls glass of wine
What are the goverment recommendations for how much alcohol men and women should consume?
- no more that 14 Units on a regular basis
What age category is alcohol consumption the highest, and do men or women consume more?
- 55-64 years old
- men = 38%
- women = 19%
What are the 4 main alcohol releated reasons why patients are admitted to hospital?
1 - alcohol Withdrawal seizures
2 - alcoholic hepatitis
3 - decompensated cirrhosis
4 - alcoholic pancreatitis
When we talk about alcohol, what do we generally refer to?
- ethanol
Can ethanol, which is alcohol be stored in the body?
- no
- it must be metabolised
Is ethanol (alcohol) water soluble?
- yes completely mixable with water
- if water is high in tissue so to is alcohol
Is ethanol (alcohol) able to pass through biological membranes?
- yes
- perfuses into tissue from blood and is dependent on H2O content
Of all the ethanol (alcohol) that we consume, how much is metabolised?
- 90%
- 10% lost in our breathe, urine or sweat
Where is alcohol generally metabolised?
- in the liver
Once ethanol (alcohol) reaches the liver, what enzymes is responsible for converting it to Acetaldehyde, and where in the hepatocytes does this occur (cytosol or mitochondria)?
- alcohol dehydrogenase (ADH)
- occurs in cytosol
Once ethanol (alcohol) reaches the liver, alcohol dehydrogenase reduces ethanol into acetaldehyde in the cytosol of the hepatocytes, which is a reversible reaction (acetaldehyde can be converted back into ethanol). What happens to ethanol to become acetaldehyde?
- 2 electrons and 2 H+ are removed from ethanol
- electrons and H+ are added to the coenzymes NAD+ forming NADH and H+
Once ethanol (alcohol) reaches the liver, alcohol dehydrogenase (reversible reaction) reduces ethanol into acetaldehyde in the cytosol of the hepatocytes, removing 2 H+ and 2 electrons and transfering them to the coenzymes NAD+, which becomes NADH. What is the next step of ethanol (alcohol) metabolism in the liver?
- acetaldehyde is converted into into acetic acid
Once ethanol (alcohol) reaches the liver, alcohol dehydrogenase (reversible reaction) reduces ethanol into acetaldehyde in the cytosol of the hepatocytes, removing 2 H+ and 2 electrons and transfering them to the coenzymes NAD+, which becomes NADH. Acetaldehyde is then converted into into acetic acid. What enzyme is responsible for this and where in the hepatocytes does this occur?
- aldehyde dehydrogenase (ALDH) (this is a reversible reaction)
- occurs in mitochondria
Aldehyde dehydrogenase (ALDH) is an enzyme that convertes acetaldehyde into acetate, which is a reversible reaction. What happens to acetaldehyde during this reaction?
- reduction of NAD+ to NADH
- 2 H+ and 2 electrons are removed from acetaldehyde
- electrons and H+ are added to NAD+ forming NADH + H+
Once acetate has been formed by the conversion of ethanol to acetaldehyde, what happes to the acetate?
- majority leaves liver and travels to peripheries
- combined with coenzyme-A
- coenzyme-A + acetate = Acetyl CoA
Once acetate has been formed by the conversion of ethanol to acetaldehyde, the majority leaves liver and travels to peripheries. Here it is combined with coenzyme-A forming Acetyl CoA. What can then happen to Acetyl CoA?
- produce cholesterol
- fatty acids
- ketone bodies
- enter citric acid cycle and form CO2
Most enzymes have a lock and key approach, meaning they are very specific to certain reactions. However, alcohol dehydrogenase has a broad specificity. Where is it found and what 3 compounds is it able to act on?
- ethanol, methanol, propanol
- located in the cytosol
What are isoforms?
- proteins that are similiar in structure and function and likley come from the same gene
- BUT some isoforms may have specific roles in the body
Why are alcohol dehydrogenase (ADH) isoforms important in the liver?
- some ADH have higher affinity for ethanol
- some may metabolise alcohol quickly and others may not
- explains why some people are drunk more easily
Methanol (CH3OH), a smaller molecule than ethanol is another substrate for alcohol dehydrogenase. What is methanol converted to in the liver?
- formaldehyde which is very toxic
- methanol is oxidised from CH3OH to CH2O
Methanol (CH3OH), a smaller molecule than ethanol is another substrate for alcohol dehydrogenase. Methanol is converted to formaldehyde, which is very toxic via oxidation using alcohol dehydrogenase from CH3OH to CH2O. The liver can then convert formaldehyde into another compound, what enzyme is responsible for this second conversion?
- aldehyde dehydrogenase
- formaldehyde converted into formic acid, which is also toxic
Methanol (CH3OH), a smaller molecule than ethanol is converted into formaldehyde, and then formic acid. Both formic acid and formaldehyde are toxic to the body. Once formic has been formed in the liver it can enter the blood stream and is especially toxic towards what cells and tissue?
- consumption of methanol can lead to blindness
- neuronal tissue causing blindness
- able to inhibt complex 4 of electron transport chain, so no water formation and reduced ATP
Due to how dangerous formic acid is, how is the body able to remove this?
- folate can be used to oxidise it
- CO2 and H2O are then formed
If a patient is suspected of consuming methanol, which can be dangerous, what could you do to reduce the risks associated with methanol?
- consume ethanol
- ethanol outcompetes methanol for alcohol dehydrogenase
- methanol can therefore not be metabolised
What is Ethylene glycol (Antifreeze) Poisoning?
- poisioning caused by drinking anti-free