Integration 1: Alcohol Metabolism Flashcards
Where does fermentation occur?
- fruits
- bacteria
- yeasts
- fungi
- mammalian muscle
fermentation vs. glycolysis vs. cellular respiration
Describe ethanol
C2H5OH is a small, volatile, water and lipid soluble molecule that easily diffuses across membranes
* dietary component that is consumed but not a nutrient
* 7 kcal/g ‘empty calories’
* up to 10% of kcals in normal diet, 50% in chronic alcoholics
* not stored and no “natural” level in the body
* structurally similar to CHO but metabolized more like lipids to acetyl CoA with RQ of 0.66 and metabolized to acetyl CoA
How is ethanol absorbed and digested?
Absorbed by rapid diffusion through the GI tract and requires no digestion
* mostly SI, about 20% in stomach
What is the rate of ethanol absorption?
about 20 min but rate can depend on food intake which acts as a barrier, alcohol concentration, how much you take in.
Where does ethanol metabolism happen?
primarily liver which has 1st pass, some in the stomach, very little in other tissues
How have humans evolved to metabolize alcohol?
evolved to express genes & isoforms to detoxify alcohol
* ethanol consumption for 1000s of years as beverage but also naturally occuring fruits
* different isoforms of the gene are required to metabolize conusmed alcohols & produced by intestinal microflora
What is the rate of alcohol metabolism?
metabolism (clearance) is slower than absorption being ~0.5oz/h of pure alcohol (~1beer)
What are the 3 pathways used to detoxify/metabolize alcohol?
- ADH (constitutive)
- MEOS (inducible)
- Catalase (minor)
What is the ADH pathway
Alcohol dehydrogenase which is the major pathway and can metabolize 80%.
* Mostly occurs in the cytosol of hepatocytes, some in gastric cells
* Used in small amounts (reccomended) of alcohol
* rate of ~0.5 oz/hr
What are the steps of the ADH pathway?
- ADH metabolizes ethanol → acetaldehyde using NAD+ & generating NADH + H+
- Acetaldehyde build up → acetic acid requires ALDH (aldehyde dehydrogenase) which needs NAD+ and generates more NADH and H+
- Final step is acetic acid + coenzyme A to form acetyl-CoA (enters mitochondria and TCA cycle) – uses ATP but also produces net ATP
What is toxic about alcohol metabolism?
The ethanol itself is toxic but acetaldehyde is even more toxic hence it needs to be converted to acetate quickly which is inert
* hangover usually combined with dehydration because hormones that retain water get suppressed and water gets excreted
* liver damage
What determines the toxic effects?
Rate of metabolism and thus detoxification of alcohol determines the toxic effects which ADH and ALDH have polymorphisms that affect the rate that acetaldehyde is generated and metabolized which differ between people.
What are ADH and ALH also important for?
There are multiple isoforms of ADH and ALDH so they are not only used to metabolize ethanol.
* some isoforms oxidze retinol (vit A) which is also an alcohol and convert it to its active form of retinal & retinoic acid important for vision, growth and differentiation.
* With acute alcohol intake there is a competitive effect creating relative deficiency of active vit A form which can be seen in fetus development
What is the MEOS pathway?
microsomal ethanol oxidizing system pathway which occurs in the ER microsomes for excessive amounts of alcohol consumption to prevent blood alcohol concentration from becoming dangerously high
* either acute or chronic
What is the reaction of the MEOS pathway?
Uses NADPH and H+ to break down alcohol in the microsome to acetaldehyde using energy from the ADH pathway and goes back into the cytosol to complete the ADH pathway.
What are the legal implications of BAC?
administrative sanctions for drivers with BAC of 0.05% to 0.079% (50 to 79 mg of alcohol per 100 ml of blood); legal limit is 0.08%
What are some responses to aocohol consumption?
What is reccomended alcohol intake for men and women?
- <1 drink/day women
- <2 drinks/day men
Alcohol associatred organ damage
