Molecular Fundamentals - Ethanol Metabolism

where is alcohol first absorbed?

in our stomach (20%)

where does the majority of alcohol go and get aborbed?

go to the intestine and get absorbed into the bloodstream via the portal vein reaching the liver and entering the hepatocyte (liver cells)

alcohol is water soluble which means what?

it is transported very rapidly to every organ of the body

where is alcohol metabolized?

hepatocytes and branch of the portal vein

alcohol leads to an excess production of what?

NADH and ROS

excess NADH and ROS can lead to what?

liver damage

NADH accumulation disrupts what?

metabolism → fatty liver, lactic acidosis, hypoglycemia

what disrupts the gut microbiome and leads to overgrowth of harmful bacteria?

ethanol consumption

lipopolysaccharide (LPS) crosses the intestinal barrier, enters the portal circulation, and activates what?

Kupffer cells (resident macrophages)

activated Kupffer cells release what?

inflammatory mediators, which can contribute to liver tissue damage

ROS buildup exceeds what?

the liver’s antioxidant defenses

ROS buildup leads to what?

cell death, fat accumulation, inflammation, and fibrosis (that results in cirrhosis - scar tissue replacing healthy hepatocytes)

how does alcohol affect glycolysis?

lowers its activity

how does alcohol affect TCA cycle?

lowers its activity

how does alcohol affect FA oxidation?

lowers its activity

how does alcohol affect lacitic acidosis?

increases its activity

alcohol metabolism produces too much NADH, which blocks energy pathways and diverts metabolism toward fat and lactate production, which can cause what?

low blood sugar, lactic acidosis, fatty liver, and eventually cirrhosis