Alcohol Metabolism & Oxidative Stress Flashcards
(44 cards)
Aldehyde dehydrogenase has a low km for acetylaldehyde, why is this good?
Km = 1/2 vmax (speed). Low Km means the toxic acetyladldehyde is converted to less damaging acetate more quickly.
what do excess NADH and acetyl coA lead to?
Changes in liver metabolism:
Fatty liver (increased Acetyl coA = fatty liver)
Alcoholic hepatitis
Alcoholic cirrhosis
What is the classic treatment for alcoholics?How does it work?
Disulfiram- It inhibits the enzyme aldehyde dehydrogenase leading to a build up of acetylaldehyde which produces hangover symptoms. Now there is a negative association with alcohol.
Why do reactive oxygen species (ROS) and reactive nitrogen species (RNS) do to cells?
Damages nuclei acids, proteins and lipids.
What is the link between oxidative stress and disease?
When cell defences such as antioxidants do not counterbalance oxidative stress can increase the risk of many disease states (Rheumatoid arthritis, Parkinson’s, Alzheimer’s.
What is a free radical?
An atom/ molecule with at least one unpaired electron
How do free radicals cause damage?
They are reactive. They ‘steal’ the electrons of other atoms/ molocules in order to provide an electron for their unpaired electron(s). This action usually generates another radical - generating more damage.
Molecular oxygen is what kind of radical?
Biradical (2 unpaired electrons)
How is superoxide formed?
Adding one electron to molecular oxygen
How can hydrogen peroxide be damaging?
Not a free radical but can react with iron (Fe) to produce free radicals. It is readily diffusable.
What is the most damaging radical?
Hydroxyl - reacts with almost anything!
What can a hydroxyl radical be reduced to form?
Water
Super oxide reacts with what to produce peroxynitrite?
Nitric oxide
Why is peroxynitrite worrying?
Not a free radical but it is a powerful oxidant that can damage cells.
How can ROS damage to DNA lead to cancer?
Can react with DNA 1. A base —> can lead to mispairing and potential mutation —>potential for cancer or
2. A deoxy/ribose sugar —>causes strand break and potential mutation on repair —> potential for cancer
How can ROS damage to proteins lead to issues?
Damages
- Backbone - fragmentation –> protein degraded
- Sidechain –> failure in repair can lead to mutation and to cancer OR to a change in protein structure (modified amino acid) such as a disulphide bond and either a loss/ gain of function or protein degradation.
When a carbon is bonded to a SH the group is called a ______ group
Thiol
Why can a ROS cause damage if takes electrons from cysteine?
Can cause inappropriate disulphide bond formation from cysteines causing misfiling, cross linking or disruption of function.
Why can lipid peroxidation be harmful to cell membranes?
Composed of phospholipids. The bilayer can be disrupted by lipid peroxidation and it’s integrity fails.
Explain the process of lipid peroxidation
- Free radical extracts hydrogen from a polyunsaturated fatty acid
- lipid radical formed which can react with oxygen to form a lipid peroxyl radical
- chain reaction formed as lipid peroxyl radical extracts H from nearby fatty acid
- hydrophobic environment of bilayer disrupted and membrane integrity fails.
Name 3 sources of biological oxidants in the human body
- Electron transport chain
- Nitric oxide synthases
- NADPH oxidases
How are free radicals created from the ETC?
Occasionally electrons escape ETC and react with dissolved o2 to form superoxide
3 different types of nitric oxide synthases?
- iNOS Inducible nitric oxide synthase (phagocytes use for direct toxic effect)
- eNOS Endothelial nitric oxide synthase (signalling- used in vasodilation of blood vessels)
- nNOs Neuronal nitric oxide synthase (signalling- neurotransmission)
What is a respiratory burst?
- Rapid release of superoxide and hydrogen peroxide from phagocytotic cells (neutrophils and monocytes).
- ROS and peroxynitrite destroy invading bacteria
