L1: Alchohol Metabolism & Oxidative Stress Flashcards
(62 cards)
Put the following in order of highest energy content:
- Fat
- Protein
- Carbohydrate
- Alcohol
- ) Fat
- ) Alcohol
- ) Protein
- ) Carbohydrate
(Carbs & proteins same)
Where is most of alcohol metabolised? How is the remainder excreted?
90% metabolised by the liver.
Remainder excreted passively in urine and on breath
Describe the process of alcohol metabolism in the liver, include:
- enzymes
- products used/generated by reaction
- ) Alcohol oxidised by alcohol dehydrogenase to acetaldehyde (NAD+ to NADH)
- ) Acetaldehyde oxidised to acetate by aldehyde dehydrogenase (NAD+ to NADH)
- ) Acetate converted to acetyl~CoA and used in:
- TCA cycle
- fatty acid synthesis
How are smaller amounts of alcohol metabolised?
- Oxidised by cytochrome P450 2E1 enzyme (CYP2E1) in liver
- Catalase in brain
What’s recommended unit intake of alcohol?
14 units/week spread over 3 days for BOTH MEN AND WOMEN.
One unit= 8g of alcohol or 2ml of pure ethanol
What’s the elimination rate of alcohol?
7g per hour (CONSTANT)
What causes a hangover?
Accumulation of acetaldehyde (a toxic metabolite)
How does acetate form acetyl~CoA?
Acetate conjugated with coenzyme A to form Acetyl~CoA
How is acetaldehyde toxicity normally kept to a minimum?
- Aldehyde dehydrogenase metabolises it into acetate as soon as it is formed
- Enzyme also has a low Km for acetaldehyde therefore
Prolonged and excessive alcohol consumption can cause liver damage due to a build up of what metabolite?
Acetaldehyde
Excess NADH and Acetyl~CoA can lead to…?
Changes in liver metabolism
A decrease in NAD+/NADH ratio results in [NAD+] being inadequate for what three things?
- Fatty acid oxidation
- Conversion lactate to pyruvate
- Metabolism of glycerol
A decrease in NAD+/NADH ration results in insufficient NAD+ for conversion of lactate to pyruvate; state two problems associated with a build up of lactate.
- ) Lactic acidosis- decreased utilisation of lactate in liver leads to accumulation of lactate in blood
- ) Decreases kidneys ability to excrete uric acid- can exacerbate gout
What is gout?
Inflammatory condition resulting from defective purine metabolism leading to increased production of uric acid. Also exacerbated by accumulation of lactate in blood as this decreases kidneys ability to excrete uric acid.
Uric acid is by-product of purine metabolism and as it’s levels in blood increase it forms monosodium crystals which accumulate in joint tissues causing pain and swelling.
What causes fatty liver?
There’s an increased availability in acetyl~CoA but it cannot be oxidised as there’s low NAD+/NADH ratio resulting in increased synthesis of fatty acids and ketones. Fatty acids are converted into triacylglycerols; these cannot be transported out of liver cells because of lack of lipoprotein synthesis- causing fatty liver.
Changes in liver metabolism can cause three diseases of liver; state these.
- Fatty liver
- Alcoholic hepatitis
- Alcoholic cirrhosis (scar tissue in liver)
Describe how chronic alcohol consumption can lead to hypoglycaemia?
Decrease in NAD+/NADH ratio; therefore, inadequate NAD+ for glycerol metabolism leading to deficit in gluconeogenesis which can cause hypoglycaemia.
How does disulfiram work as a treatment for chronic alcohol dependence?
Inhibits aldehyde dehydrogenase. When a patient drinks, acetaldehyde will accumulate causing symptoms of a hangover and therefore ‘putting the patient off’ having an alcoholic drink
Define oxidative stress.
Imbalance of free radicals/oxidants (e.g. ROS, RNS) and body’s defence mechanisms against free radicals.
What’s a free radical?
Atom or molecule that contains one or more unpaired electrons and is capable of independent existence
Are radicals reactive?
Free radicals usually very reactive- acquire electrons from other atoms, molecules or ions. Reaction of a radical with a molecule typically generates a second radical thereby propagating the damage
State three reactive oxygen species (ROS’s) and two reactive nitrogen species (RNS’s).
ROS= superoxide radical (O2 -) & hydroxyl radical & hydrogen peroxide RNS= nitric oxide radical (NO) & peroxynitrite (ONOO-)
How is superoxide formed?
Adding electron to molecular oxygen
How is hydroxyl radical formed?
Addition of H+ and e- to hydrogen peroxide (forms hydroxyl radical and water)