S1 L1 - Alcohol metabolism and Oxidative stress Flashcards
- *Alcohol metabolism**
- How is the majority of alcohol metabolised? (equation)
- What happens to the product?
- How is the remainder of alcohol excreted?
- Recommended limits of alcohol
- Rate of alcohol metabolism (per hour)
- Liver damage: What does the body do to try and stop liver damage (liked to the equation in bullet point 1)
- How is the majority of alcohol metabolised? (equation)
Metabolised in the liver (see attached picture with equation)
—– alcohol oxided by alcohol dehydrogenase to acetaldehyde and then to acetate by aldehyde dehydrogenase
- What happens to the product?
Acetate is converted to acetyl-Co A and used in TCA cycle or for fatty acid synthesis
- How is the remainder of alcohol excreted?
Urine and breath
- Recommended limits of alcohol:
14 units/week spread over at least 3 days for BOTH men & women
- Rate of alcohol metabolism (per hour):
One unit of alcohol = 8 g • Eliminated at rate of ~7g per hour
- Liver damage: What does the body do to try and stop liver damage (linked to the equation in bullet point 1):
Acetaldehyde toxicity normally kept to a minimum by aldehyde dehydrogenase (low Km for acetaldehyde) -> Prolonged and excessive alcohol consumption can cause sufficient acetaldehyde accumulation to cause liver damage -> Excess NADH and Acetyl-CoA lead to changes in liver metabolism
Metabolic response to chronic alcohol consumption
- 4 effects
Types of liver damage
Metabolic response to chronic alcohol consumption
Types of liver damage:
Fatty liver, Alcoholic hepatitis, Alcoholic cirrhosis
(pic below)
What is the treatment of alcohol dependence?
How does this medication work?
What is the treatment of alcohol dependence?
Disulfiram
How does this medication work?
Picture below
- *Oxidative stress**
- Define
- Diseases associated with oxidative stress
- Free radicals
Define oxidative stress: An imbalance in cell damage and cell defences (anti-oxidants)
Diseases: Cardiovascular disease, crohn’s disease, cancer, rheumatoid arthritis, pancreatitis, multiple sclerosis
Free radicals:
• Electrons of atoms, molecules & ions usually associate in pairs. Each pair moves within a defined region of space (an orbital)
• A free radical is an atom or molecule that contains one or more unpaired electrons and is capable of independent (“free”) existence
• Free radicals (usually) very reactive and tend to acquire electrons from other atoms, molecules or ions
Reactive oxygen species and Reactive nitrogen species
- Starting with oxygen
What groups of ‘molecules’ can ROS damage
- DNA - How can ROS damage DNA
- DNA
- Protein
- Lipids
- DNA - How can ROS damage DNA
(pic attached)
- Proteins - How can ROS damage protein?
- Lipids - How can ROS damage lipids?
- Proteins - How can ROS damage protein?
-
Lipids - How can ROS damage lipids?
• Free radical (e.g. •OH) extracts hydrogen atom from a polyunsaturated fatty acid in membrane lipid
• Lipid radical formed which can react with oxygen to form a lipid peroxyl radical
• Chain reaction formed as lipid peroxyl radical extracts hydrogen form nearby fatty acid
• Hydrophobic environment of bilayer disrupted and membrane integrity fails
(picture attached)
Disulphide bonds - How can these form do to ROS?
- Where do they form between?
- What happens if inappropriate disulphide bonds form
- Play important role in folding and stability of some proteins (usually secreted proteins or in extracellular domains of membrane proteins)
- Formed between thiol groups of cysteine residues
- Inappropriate disulphide bond formation can occur if ROS takes electrons from cysteines causing misfolding, crosslinking and disruption of function (e.g. enzyme)
Causes cellular damage:
Sources of biological oxidants
- 2 main groups… 3 examples of each
Cellular defences:
3
Cellular damage:
2 main groups:
- Endogenous: NADHP oxidase, nitric oxidase synthase, electron transport chain
- Exogenous: Pollutants, Drugs (e.g. Primaquine - anti-malarials), Radiation (x-ray, UV light), Toxins (herbicide)
Cellular defences:
- Superoxide dismutase and catalase
- Glutathione
- Free radical scavengers
Cellular damage:
1. Electron transport chain is a source of ROS
Cellular damage:
2. Nitric oxide synthase
Cellular damage:
- Respiratory burst
- Reactions
- Disease associated
Cellular Defences
- Superoxide dismutase and catalase
- Reaction
Cellular defences:
2. Glutathione
- *Pentose phosphate pathway**
- Why is this pathway essential for glutathione defence
- start and end product
- source of _______
- End product used in…..
- Main enzyme
Cellular defences:
3. Free radical scavengers
Galactosaemia
- Pathway
- Three enzymes
- Other pathway
- Symptoms
G6PDH Deficiency
- what does this mean for glutathione cellular defence
- set of reactions to show this
- *Metabolism of paracetomol**
- Where does this occur (which organ)?
- What is the equations
- Drug used in a paracetomol overdose
