Metabolic And Nutritional Aspects Of Alcohol

Question 1

Oxidation of ethanol

Answer 1

. 2-10% lost in breath and/or urine
. Absorbed fast and metabolized slowly as it does not need transport proteins to move across membranes
. 80-90% oxidized in liver, some in stomach

Question 2

Pathways of alcohol metabolism

Answer 2

. Alcohol dehydrogenase (ADH) of the cytosol (stomach and liver)
. Microsomal ethanol oxidizing system in ER (liver)
. End w/ production of toxic metabolite acetaldehyde

Question 3

Alcohol dehydrogenase pathway

Answer 3

. First pass metabolism in stomach
. Converts ethanol to acetaldehyde
. All ADH (high and low Km) are activated after alcohol ingestion due to high gastric concentration
. This pathway dec. bioavailability and acts as protective barrier against systemic effects when alcohol is consumed in small amounts

Question 4

What conditions have a dec. in stomach ADH activity?

Answer 4

. Alcoholic individual that develop gastritis

Question 5

Why women have smaller alcohol tolerance than men

Answer 5

. Smaller body size and distribution of alcohol in smaller water space bc women higher proportion of fat
. Women have less gastric ADH activity than men, w/ less alcohol broke. Down in stomach, more enters blood stream

Question 6

Effect of alcohol on carb and lipid metabolism

Answer 6

. ADH mediated generation of NADH in liver
. Overwhelms liver’s capacity to maintain redox homeostasis and can result in metabolic issues
. Lactic acidosis reduces capacity of kidney to excrete uric acid leading to secondary hyperuricemia
. Hyperuricemia explains why gout acts up w/ alcohol
. Rxns catalyzes by TCA cycle are slowed due to. Rxns that require NAD
. Mitochondria uses H equivalents from alcohol instead of FAs in liver causing hypoglycemia
. Can result in fatty liver as FAs aren’t used

Question 7

Metabolism of alcohol via microsomal ethanol oxidizing system (MEOS)

Answer 7

. Liver microsome site for adaptive ethanol oxidation (MEOS)
. Enzyme CYP2E1 highly induced in chronic alcohol consumption
. Contributes to metabolic tolerance that develops in alcohol dependence
.

Question 8

Ethanol-drug interactions

Answer 8

. Inc. alcohol conc. Inhibits drug metabolism in liver and ADH in stomach
. In chronic users the liver MEOS are highly induced and enhances metabolism of certain drugs

Question 9

MEO induction toxicities

Answer 9

. Cytochrome P450 oxidase can convert exogenous compounds to toxic compounds, inc. vulnerability to these compounds in alcoholism
. Enhanced metabolism pertains to variety of prescribed drugs and over the counter medication (analgesics that are inducers of E21)
. Effects of Tylenol and ethanol are synergistic bc they deplete levels of reduced glutathione

Question 10

Inc. in P4505E21 may partially account for ___

Answer 10

. Inc. incidence of cancer in persons w/ alcohol use disorder
. Testicular atrophy
. Gynecomastia

Question 11

Effect of acetaldehyde and acetate

Answer 11

. Ethanol converted into these
. Aldehyde dehydrogenase (ALDL) is mitochondrial enzyme w/ low Km for acetaldehyde, activity reduced by chronic alcohol consumption
. Imbalance in production and disposition of acetaldehyde resulting in high tissue and blood levels of acetaldehyde
. It is highly reactive and cellular proteins are damaged from ROS damage

Question 12

Disulfiram

Answer 12

. Found some use in patients wanting to stop alcohol ingestion
. Conditioned avoidance res[onse induced so patient abstains from alcohol to prevent unpleasant effects from drug mixed w/ acetaldehyde accumulation
. Symptoms: flushing, tachycardia, hyperventilation, nausea