10 - Alcohol Flashcards
Why was alcohol first used as a beverage?
Because it provided energy, some nutrients and was safer than untreated drinking water (antibiotic properties)
Define an ‘alcohol’
An organic molecule containing an OH hydroxyl group
What is the chemical formula of the common drinkable alcohol? What is it called?
CH3CH2OH - Ethanol
What is the name for CH3OH?
What is the name for 2CH2OH?
What is CH3OH - methanol - wood alcohol
What is 2CH2OH - ethane-1,2 diol/ethylene glycol - antifreeze
What is the product of methanol breakdown that makes it toxic?
Formaldehyde
How does alcohol reach the liver?
delivered by hepatic portal system
How much alcohol does a healthy adult metabolise per hour?
1 unit - 8g / 10ml
What’s the legal blood alcohol limit?
80mg per 100ml (0.08%)
Why do women have a higher peak alcohol concentration than men?
Women have lower body fluid % than men
Women have lower gastric ADH levels
difference in first-pass metabolism
Why does the concentration of ethanol rise quickly in the central nervous system?
The brain receives a large proportion of total blood flow
ethanol readily crosses biological membranes - polar molecule but small
What are the 3 oxidation products of alcohol (ethanol)
Ethanol -> Acetaldehyde -> Acetate -> Acetyl CoA
What are the 3 enzymes of alcohol oxidation?
Alcohol dehydrogenase (ADH) Microsomal ethanol oxidising system (MEOS) Aldehyde dehydrogenase (ALDH)
What is the primary enzyme for alcohol oxidation at low blood alcohol levels? Why?
Alcohol dehydrogenase (ADH) As it has a high affinity, but low capacity due to depletion of NAD+
What is the primary enzyme of the MEOS system? What is the coenzyme?
Cytochrome P450 subtypes
NADPH coenzyme
What are the complications of MEOS activity associated with chronic alcohol consumption?
Increase in ethanol metabolism (tolerance)
Increase in drug metabolism (if they usually eliminated by cytochrome P450)
Toxic by-products -> liver diease
What is the role of Acetaldehyde dehydrogenase (ALDH) in the liver?
What is it inhibited by?
Converts acetaldehyde to acetate
Inhibited by disulfiram
ADH is ___ affinity, ___ capacity enzyme
Provides a slow but relatively safe way to _____ alcohol
Can process about _ units per hour
ADH is high affinity, low capacity enzyme
Provides a slow but relatively safe way to oxidise alcohol
Can process about 1 unit per hour
MEOS is a ___ affinity, ___ capacity pathway
Induced by ___ alcohol levels
Provides a ___ but relatively dangerous way to oxidise alcohol
____ are also produced that damage liver cells
MEOS is a low affinity, high capacity pathway
Induced by high alcohol levels
Provides a faster but relatively dangerous way to oxidise alcohol
Reactive oxygen species (ROS) are also produced that damage liver cells
What is first-pass metabolism?
A small amount of alcohol is oxidized in the stomach before being absorbed into the bloodstream.
What are the routes for Acetyl CoA metabolism?
1) Transprted to TCA cycle and then oxidised in the electron transport chain to provide energy
2) Converted to fatty acids and stored
What is the irreversible step that means that acetyl CoA cannot be used to synthesise glucose?
Acetyl coA cannot be converted to pyruvate due to pyruvate dehydrogenase enzyme.
What is functional tolerance?
the individual shows few signs of intoxication even at high blood alcohol levels
What is the active compound found in red wine and grapes that may have beneficial effects?
Resveratrol - phytochemical.
Lowers risk for diabetes, heart disease and liver disease. Some antioxidant properties.
Why does moderate-high alcohol intake cause problems with drug metabolism?
MEOS cytochrome P450 levels increase, which is also involved in metabolism of theraputic drugs.
Especially SYP2E1
Drugs metabolised by the enzyme are metabolised more quickly, reducing benefits+ toxic compounds can build.
What is the toxic metabolite produced in the breakdown of paracetamol?
NAPQ1
What is the effect of increased ADH on NAD+, what are the metabolic consequences of this?
ADH consumes NAD+ and produces NADH
High conc of NADH inhibit TCA cycle
Depletion of NAD+ means liver cannot synthesise glucose during normal starved periods.
Consequence = release of acetate and ketone bodies
What is the consequence of the MEOS pathway consuming NADPH? (3)
Generates free radicals
Depletes cellular glutathione pool (maintains redox states)
Increased drug toxicity
What is the blood alcohol concentration that can result in loss of conciousness, coma, suppression of respiratory response and death?
0.40% and above
What are the main causes of the alcoholic hangover? (3)
1) Alcohol is a diuretic, elevates fluid and electrolyte excretion leading to dehydration
2) Irritates the stomach lining causing excessive acid secretion leading to nausia
3) Disrupts energy metabolism, causes excess NADH production, increases lactic acid (aches)
What is Wernicke-Korsakoff syndrome?
Associated with thiamin deficiency
Characterized by paralysis of external eye muscles and confusion -> coma -> death
