Alcohol Metabolism Flashcards
Where is most of alcohol metabolised?
The liver
What happens to the alcohol that is not metabolised?
Excreted in urine and breath
What oxidises alcohol?
Into what?
Alcohol dehydrogenase
Acetaldehyde
What oxidises acetaldehyde?
Into what?
Aldehyde dehydrogenase
Acetate
What is acetate converted into?
Acetyl CoA
What is acetyl CoA used in? (2)
TCA cycle
Fatty acid synthesis
If alcohol isn’t oxidised by alcohol dehydrogenase what can it be oxidised by?
Catalase in the brain
Cytochrome P450 2E1
What is the recommended alcohol consumption?
14 units
Spread over at least three days
What is the rate of alcohol elimination?
7g per hour
How many grams is one unit of alcohol?
8g
What causes a hangover as well as dehydration?
Accumulation of acetaldehyde - which is toxic
What enzyme controls the levels of acetaldehyde?
How?
Aldehyde dehydrogenase
Has a low Km for acetaldehyde - high affinity
What is the primary cause of liver damage?
Prolonged and excessive alcohol consumption
Acetaldehyde accumulation
What causes changes in liver metabolism?
Excess NADH
Excess Acetyl CoA
Three key conditions that effect the liver, caused by excessive alcohol consumption
Fatty liver
Alcohol hepatitis - inflammation of the liver
Alcohol cirrhosis - the liver has become significantly scarred
What drug is used in the treatment of alcohol dependence?
Disulfiram
How does disulfiram work?
Inhibits aldehyde dehydrogenase
Acetaldehyde accumulates if alcohol drunk - causing nausea
Explain how increased NADH effects liver metabolism (3)
- NAD+ levels inadequate for fatty acid oxidation
- Less lactate converted to pyruvate
- Lactate accumulate in the blood
How is the electron transport chain a source of ROS?
E- can escape the chain and react with dissolved O2
To form superoxide
What are the three types of NOS?
What do they all do?
INOS - inducible - produces high NO conc in phagocytes for direct toxic effect
ENOS - endothelial - signalling
NNOS - neuronal - signalling
What is NOS?
Nitric oxide synthase
Toxicity of NO* (nitric oxide)
Toxic at high levels
Role of NO* (2)
Vasodilation
Neurotransmission
What occurs in respiratory burst? (2)
- Rapid production of superoxide and H2O2 - from phagocytic cells
- The bacteria around the cell are destroyed (sometimes the phagocytic cells are too)
What enzyme is required in respiratory burst?
Where is it found?
What does it do?
NADPH oxidase
Present in membrane of phagosomes
Transfers e- from NADPH to O2 - to make superoxide radicals
Link defect in respiratory burst process to a disease
Genetic defect in NADPH oxidase
Enhanced susceptibility to bacterial infects
(Pneumonia, abscesses…)
What are two enzymes in cellular defence against ROS and RNS
Superoxide dismutase
Catalase
How does superoxide dismutase work?
Converts superoxide (O2*-) to H2O2 and O2
How does catalase work (in defences against oxidative stress)?
What type of cells are they prominent in?
Converts H2O2 to H2O and O2
Immune cells
What is another cellular defence of a cellular defence?
Glutathione (GSH)
How does glutathione act as a cellular defence?
The structure is GLY-CYS-GLU
The thiol group of Cys donates e- to ROS + reacts with another GSH to form a disulphide bond - now GSSG
What enzyme is required in the bonding of two Cys molecules during glutathione cellular defence?
What does it require?
Glutathione peroxidase
Selenium
What is required to reduce GSSG back to GSH?
How does it work?
Glutathione reductase
Catalyses the transfer of e- from NADPH to disulphide bond of GSSG
Resulting in GSH
What is the main source of NADPH?
Pentose phosphate pathway
Name two free radical scavengers
Name their solubilities
Where they are important
Vitamin E - lipid soluble, protection against lipid peroxidation
Vitamin C - water soluble, regenerate reduced form of vitamin E!
How do free radical scavengers work?
Reduce free radical damage
Donate H atom and its electron to free radicals in non enzymatic reactions
Name the ROS and RNS
O2*- superoxide
H2O2 hydrogen peroxide
*OH hydroxyl radical
NO* nitric oxide
ONOO- peroxynitrite
How do Heinz bodies form?
G6PDH deficiency
Less NADPH produced in Pentose phosphate pathway
Less GSH reformed
Haemolysis - cross linked haemoglobin form Heinz bodies
What is a clinical sign of G6PDH deficiency?
Heinz bodies
What do Heinz bodies do?
Bind to membrane
Altering structure of RBC
RBC can’t fit through small capillaries
How do anti-malarials effect ROS?
Deplete NADPH
GSH not reformed
Why are RBC more susceptible to oxidative stress?
In RBC the only way of getting NADPH is through pentose phosphate pathway
What can small amounts of alcohol be metabolised by?
P450 enzymes
Catalase in the brain
What is the rate of alcohol metabolism?
7g/hr
What processes would increase in chronic excessive alcohol consumption?
Synthesis of fatty acids and ketone bodies
