alcohol metabolism

what deficiency is alcohol metabolism commonly associated with

vitamin

dietary alcohol guidelines for women

less than 1 drink per day

dietary alcohol guidelines for men

less than 2 drinks per day

what is the dietary guidelines that equals 1 drink

½ oz of ethanol

12 oz beer

12 oz seltzer

5 oz wine

1.5 oz 80 proof liquor

1 oz 100 proof liquor

calories for alcohol

7 kcal/g

density of ethanol

0.8 g/mL

steps for calculating calories from ethanol in a drink

convert oz or drink to mL (1oz=30mL)

multiply by ABV

multiply by density of ethanol (0.8g/mL)

multiply by kcal (7kcal/g for ethanol)

3 systems of alcohol metabolism

alcohol dehydrogenase

microsomal ethanol oxidizing system (MEOS pathway)

Catalase

catalase utilizes what for alcohol metabolism

hydrogen peroxide

catalase accounts for what % of alcohol metabolism in the body

less than 2%

main enzyme for ethanol breakdown

alcohol dehydrogenase (ADH)

where is ADH located

gastric mucosal cells

hepatocytes

ADH function

converts alcohol into an aldehyde

requires NAD→NADH pathway

used in reactions:

ethanol → acetaldehyde

retinol → retinal (vitamin A)

sex difference for ADH production

women make more than men

ethnic difference for ADH production

asian descent makes less than Northern European descent

why do heavy drinkers sometimes suffer from night blindness?

because they use so many enzymes for ethanol → acetaldehyde conversion that they dont have enough left for retinol → retinal conversion

is alcohol or acetaldehyde lethal

alcohol

what does acetaldehyde do in the body

toxic (but not lethal)

can bind to proteins inhibiting function (including enzymes)

promotes fibrosis of liver leading to cirrhosis (fatty liver)

systemic inflammation (hangover)

acetaldehyde dehydrogenase location

liver

acetaldehyde dehydrogenase function

covert acetaldehyde to acetate requiring NAD

problems with the ADH-acetaldehyde dehydrogenase pathway

1. saturation of the enzymes: consuming more than enzymes can handle causes ETOH floats in blood stream which leads to intoxication and damage of cell membrane

2. depletion of NAD

secondary pathway of alcohol metabolism

MEOS (Microsomal Ethanol Oxidizing System)

MEOS location

smooth endoplasmic reticulum

what pathway is MEOS most similar to

ETC

important protein for MEOS

cytochrome P450

important cofactors for MEOS

riboflavin (FAD and FMN) and niacin (NADPH)

end products of MEOS

water, NADP (doesnt provide energy), acetaldehyde

inducible

pathway can increase its activity with repeated exposure

MEOS inducibility

normally a minor pathway for alcohol metabolism but with chronic alcohol consumption, the body makes more of the cytochrome P450 enzyme and increases the smooth ER which increases the pathway’s activity

So the system is upregulated by alcohol exposure

what else does MEOS pathway breakdown

xenobiotics (drugs prescribed or not prescribed)

why do labels say not to consume alcohol while taking xenobiotics

alcohol and xenobiotics are metabolized by the same pathway (MEOS) so they fight for enzyme use → more alcohol in bloodstream causes more intoxication

where is the acetate that is produced from alcohol metabolism turned into acetyl CoA

liver (mostly)

muscle

brain (sometimes)

heart

consequences of induced (unregulated) MEOS pathway

• increases alcohol tolerance

• alters drug metabolism

• increases risk of toxicity (of drugs and alcohol) through toxic metabolite products

acetate fates after its production in liver

1. stays in liver

2. enters blood stream

what happens when acetate stays in liver

converted to acetyl CoA (CoA added)

de novo fatty acid synthesis

fatty acids stay in liver or enter blood through VLDL

what happens when acetate enters blood stream

signals decrease of FA and TG release from adipose (the few that are released travel to liver for cleanup)

enters muscle tissue where it is the priority conversion to acetyl CoA and oxidized to energy

what happens to other metabolic processes in order to metabolize alcohol

1. other processes are slowed down: gluconeogenesis, protein synthesis, Krebs cycle, glycolysis

2. some processes are sped up: FA synthesis, ketone formation

3. high NADH:NAD ratio so pyruvate is converted to lactate in order for lactate dehydrogenase can turn NADH into NAD to balance out the ratio

why does the body prioritize acetate oxidation over FA or TG breakdown for energy

it is able to be broken down even faster for energy

gastrointestinal tract role in alcohol metabolism

stomach = increased HCl secretions

acetaldehyde is toxic especially to mucosal cells so it decreases intestinal absorption of almost all vitamins, especially B vitamins

increase absorption of iron

increases risk of GI cancers

kidney role in alcohol metabolism

increased excretion of Mg, K, Ca, Zn

decrease in antidiuretic hormone production = diuresis

brain role in alcohol metabolism

decreased oxygen

shuts down → loss of consciousness

short and long term changes: memory loss, dementia, depression and or anxiety

consequences of alcohol consumption in the liver

fatty liver

hepatic disease (cirrhosis)

lactic acidosis

main storage site for vitamins and conversion site of vitamins to active form

liver

symptoms of hangover

dehydration

low blood sugar

treatment/ prevention of hangovers

CHO containing food

B vitamins before drinkning

OTC analgesics (Tylenol, NSAIDs, ibuprofen)

antioxidants

what does more ADH lead to

more acetaldehyde produced, less ETOH in liver

what does less ADH lead to

less acetaldehyde produced, more ETOH in liver → more intoxication

how does food play a role in alcohol metabolism in the stomach

empty stomach leads to less ETOH breakdown in the stomach, more ethanol diffusion into blood and then into liver, causing intoxication

more food in the stomach allows for ETOH to stay in stomach for breakdown to acetaldehyde and causes less intoxication