Alcohol Flashcards
What are the properties of alcohol?
ethyl alcohol = ethanol
- lipophilic property (solubility)
- NOT a nutrient
- 7.1 kcal/gram
- metabolic energy depends on the amount of intake
- 5- 10% of energy in an average diet
How does alcohol pass through the GI tract?
After uptake, no digestion
- Ethanol occurs in free form => no separation from larger molecules or ‘food matrix’ is required
- Ethanol can be directly absorbed
Direct absorption by diffusion -> in gastric mucosa, small intestine
Consumption on an empty stomach:
- faster absorption
- affects gastric mucosa -> can cause acute gastritis
What is ethanol metabolism?
Ethanol travels to the liver = the site of ethanol
90% of absorbed ethanol metabolized in hepatocytes
- through diffusion
Other sites for ethanol excretion:
- lungs and kidney
- sweat
What is the main pathway of ethanol oxidization?
Alcohol dehydrogenase (ADH) pathways => in the cytoplasm
1 mole of ethanol
-> 2 mole NADH + H+ -> transported into mitochondria via malate-aspartate-shuttle -> enter electron transport chain -> formation of 5 ATP
Acetaldehyde dehydrogenase (ALDH) => mitochondria
-> acetate -> acetyl-CoA -> TCA cycle or fatty acid synthesis
What is the alternative pathway of ethanol oxidation?
Microsomal ethanol oxidizing system MEOS:
- inefficient formation of energy
- smooth endoplasmic reticulum
Ethanol is simultaneously oxidized with NADPH in the electron transport system
Substrates oxidized by MEOS: ethanol, fatty acids, steroids, barbiturate
- ethanol -> synthesis of cytochrome-450
- chronically high ethanol consumption -> system more active
- hepatocytes -> metabolize ethanol more effectively
- metabolic tolerance for ethanol
- intoxication is only observed after consumption of higher amounts
Chronic, high consumption affects
- fatty liver
- liver cirrhosis
- cancer of the GI tract
- lactic acidosis
- metabolic tolerance
- overweight
- weight loss
- fetal alcohol syndrome
Potential underlying mechanism for alcohol-disease relationship:
- Excess foramtion of NADH + H+
- Acetaldehyde toxicity
- Metabolic tolerance
Excess foramtion of NADH + H+
NADH: NAD+ ratio
- NADH => important regulator in dehydrogenase reactions -> will favour NAD+ production
- lactic acidosis => competition for exertion from the kidney with uric acid
- TCA cycle activity decreased => acetaldehyde -> acetate -> acetyl-CoA enter TCA cycle; acetyl cannot enter TCA cycle so excess acetyl-CoA enters the fatty synthesis
- reduction of dihydroxyacetone (DHAP) to glycerol-3-phosphate is favoured -> increases fatty acid synthesis and glycerol formation -> inc. formation of triacylglycerol
- glucogenic amino acids -> favour formation of glutamate over alpha-ketoglutarate -> depletion of alpha-ketoglutarate -> impaired gluconeogenesis from amino acids
Acetaldehyde toxicity
Excess Acetaldehyde -> inhibits protein synthesis and protein secretion
- attached to enzymes
- impedes formation of microtubules in liver cells that are required for secretion of VLDL
- reduced liver function
- formation of cirrhotic tissue
- reduced lipid removal = calculation of fat in the liver
Moderate consumption:
- reduced risk of cardiovascular disease
- increase in HDL
- Mixed results
How does it reduce the risk of cardiovascular disease?
Moderate consumption of alcohol shown to increase HDL
- different alcohol sources come with different constituents
“French paradox” - high consumption of saturated fats but a low rate of coronary artery disease -> red wine -> polyphonic compounds suggested to inhibit LDL oxidation and thereby atherosclerotic progress
J-shaped Curve
association between alcohol intake and risk of mortality
- moderate alcohol consumption is beneficial regarding mortality and chronic disease risk compared to alcohol abstinence or alcoholism
- y-axis => mortality
- x-axis => alcohol intake
