ethanol metabolism Flashcards
calories from ethanol
- 4th major nutrient that provides energy
- empty calories because they have no nutritional value
- 98 grams per drink for ethanol only!
lifestyle choice death
- smoking
- obesity
- alcoholism
alcoholism is the IMMEDIATE cause of what?
-liver cancer
What is the first organ effected by alcoholism?
liver
why is ethanol easily absorbed by intestine and readily entered into the blood stream?
- water and fat soluble
- requires no digestion or enzymes to break it down
why do we have an enzyme that specifically works on alcohol?
-intestinal flora use fermentation so we developed the enzyme to handle ethanol
Majority of ethanol is matabolized…
in the liver by two different pathways
- ADH
- MEOS using cyt-P450 enzymes
ADH system
- does not use energy
- ADH makes toxic acetaldehyde, ALDH turns that into acetate
- acetate goes into blood then goes to acetyl CoA in muscles for TCA cycle
what is the rate-limiting step in ADH system?
-ADH (alcohol dehydrogenase)
What is the limiting factor for alcohol metabolism?
-NAD+ availability
Zero order kinetics
-a constant amount of drug is eliminated per unit of time
Km of ADH
- 1mmol/L
- saturated after one drink
- if you continue to drink, it stays in the blood stream until the enzyme is done breaking down the first drink
generally, people metabolize…
10g of alcohol per hour
-blood alcohol level decreases 0.15g/L every hour
atypical ALDH
- eat asians
- single amino acid substitution (Glu to Lys)
- dominant negative
- oriental flush
What accumulates with atypical ALDH?
- toxic acetaldehyde
- cant turn it into acetate
Disulfiram
- inhibits aldehyde dehydrogenase(ALDH)
- accumulation of acetaldehyde
- used in treatment for alcoholics
What happens if a person keeps drinking past the pain on disulfiram?
-damage caused by acetabldehyde that is seen in long time alcoholics will be ACCELERATED
processing of alcohol produces a large amount of…
NADH in the liver
Why is a build up of NADH so bad?
- can alter many metabolic processes
- significant effects are found in heavy drinkers of binge drinkers
build up of NADH in well fed state
- liver is taking up glucose and performing glycolysis, producing NADH and pyruvate
- adding more NADH to this amount will inhibit PDH complex and force it into pyruvate
- lactic acidosis and hyperuricemia
build up of NADH in fasting state
- liver will try to perform GNG, but NADH inhibits it so it is diverted to lactate
- hypoglycemia
is alcohol a substrate for GNG?
****
- nope
- it is ketogenic, not glucogenic
hyperlipidemia
- NADH inhibits oxidation of fatty acids
- accumulation of TAG as liquid droplets
- fatty liver disease which can lead to hyperlipidemia
Acetyl CoA and build up of NADH
- NADH inhibits TCA cycle
- OAA is converted back into malate to generate NAD+
- Acetyl CoA is forced into ketone synthesis and can result in ketoacidosis
