Alcohol Metabolism

Question 1

Oxidation of Ethanol

Answer 1

when present, alcohol becomes preferred fuel displacing all others

Question 2

Ethanol oxidaion

Answer 2

does not need transport protein just gets into water spaces easily
absorbed FAST, metabolized SLOW
80-90% oxidized in liver

Question 3

two main pathways for ethanol metabolism

Answer 3

alcohol dehydrogenase (stomach and liver)
microsomal ethanol oxidizing system (liver)

Question 4

Both pathways of ethanol metabolism produce

Answer 4

acetaldehyde highly toxic

Question 5

ADH pathway

Answer 5

first pass metabolism of alcohol occurs in stomach
3 different forms of ADH in stomach (high Km or low Km for ethanol)
even high Km ADH is activated after alcohol ingestion due to high gastric etahnol conc. and sig. metabolism results

Question 6

first pass metabolism decreases bioavailability of ethanol

Answer 6

protective barrier against systemic effects
break down alcohol in somtach reduces blood alcohol conc so not as much needs to be metabolized
this is lost in alcoholics

Question 7

effects of carb and lipid metabolism

Answer 7

NADH overwhelms livers capacity to maintain redox homeostasis
NADH is product from breakdown of alcohol
normally NAD+/NADH is high in liver
alcohol shifts this balance in the liver

Question 8

ethanol –> acetaldehyde –> acetate
forming NADH each time

Answer 8

NADH feeds ETC and makes ATP
if excess NADH, increase Acetyl coA leads to fatty acid synthesis

Question 9

excess NADH converts pyruvate to

Answer 9

-lactate causes blood to be acidic
kidney acidosis and cannot excrete uric acid and can have gout
- increase fatty acid
fatty liver

Question 10

lactate is gluconeogenesis substrate
lactate cannot be converted to pyruvate bc

Answer 10

lack of NAD+

Question 11

liver microsomes are sites for ___ system of ethanol oxidation named MEOS

Answer 11

adaptive

Question 12

these enzymes belong to the class of cytochome P450 oxidases and oxidation of alcohol involves a specific form of cytochrome P450 oxidase called

Answer 12

2E1

Question 13

2E1 is highly induced with chronic consumption

Answer 13

contributes to metabolic tolerance that develops in individuals with alcohol dependence disorder

Question 14

under what conditions is P4502E1 effective?

Answer 14

when large amounts of alcohol consumed

Question 15

in what individuals is P4502E1 most effective?

Answer 15

in individuals with alcohol dependence

Question 16

ethanol-drug interactions
in social drinker

Answer 16

drug inhibits alcohol oxidation in stomach and blood alc conc increases
liver has ADH and microsome enzymes: alc gets first dibs and oxidized first and drugs go thru cytocrome P450 drug levels will be high

Question 17

Ethanol-drug interactions
chronic drinker

Answer 17

drugs broken down really fast
ends up with toxicity bc drug efficicacy is reduced
gastric ADH decreases resulting in decreased ethanol metabolism in stomach
liver MEOS highly induced

Question 18

Drug metabolism
phase 1 and 2

Answer 18

phase 1 CYPs 5% NAPQ1 (extremely toxic)
phase 2 conjugation/hydrolysis - sulfatoin, acetalyation 95%

Question 19

alcohol reduces glutathion levels, resutling in

Answer 19

increased free radical mediated damage

Question 20

NAPQ1 is produced in larger quantities when

Answer 20

2E1 is highly induced

Question 21

increase in P4502E1 may partially account for

Answer 21

increased incidence of cancer in persons with alcoholism
testicular atrophy
gynecomastia

Question 22

aldehyde dehydrogenase converts

Answer 22

acetaldehyde to acetate

Question 23

ALDL activity is reduced on chronic alcoholism

Answer 23

acetaldehyde becomes major end product accumlating in tissues and blood and it is highly reactive

Question 24

the intrinsic toxicity of alcohol responsible for

Answer 24

deficiencies seen with alcoholism
as well as with impaired utilization and malabsorption/maldigestion bc organs damaged

Question 25

Thiamin deficiency

Answer 25

primarily due to impaired absorpiton
wernicke korsakoff syndrome seen in alcoholics due to severe thamin def
characterized by ataxia, confusion, opthalmoplegia

Question 26

deficiencies with alcoholism

Answer 26

folic acid
pyridozine
vitamin A

Question 27

alcoholic cirrhosis result of both

Answer 27

malnutrition and direct toxic effect of alcohol

Question 28

treatment for alcoholism

Answer 28

disulfiram causes accumulation of acetaldehyde resulting in flushing, tachycardia, hyperventilation and nausea
it inhibits second rxn from acetaldehye to acetate
you associate side effects with drinking so they stop