Although consumption of alcohol leads initial sense of euphoria and well-being, but on long term use it leads to many complications. One of the initial complications associated with chronic alcohol intake is FATTY LIVER.
One of the causes for alcohol induced fatty liver is the metabolic changes that alcohol does to hepatocytes!! Generally 85%-95% of alcohol is metabolized in the liver by alcohol dehydrogenase (ADH) enzyme to acetaldehyde (a toxic by product of alcohol. Acetaldehyde is metabolized in the mitochondria of hepatocytes by aldehyde dehydrogenase (ALDH) enzyme into acetate. Acetate is released into circulation and is taken up by extra-hepatic tissues particularly skeletal muscle.
Both ADH and ALDH catalyzed reactions each will generate NADH+H. This increases the levels of NADH+H levels both in mitochondria and cytosol. Now what’s the big deal about it!! This is the main reason for the development of fatty liver!!
Elevated levels of NADH+H will decrease citric acid cycle in mitochondria which leads to accumulation of acetyl CoA. Acetyl CoA gets out of mitochondria as citrate and in cytoplasm citrate is converted back to acetyl CoA. Acetyl CoA now in cytoplasm gets into fatty acid synthesis pathway leading to increased fatty acid formation.
Fatty acids will combine with glycerol to make triacylglycerol. This fatty acid containing triacylglycerol will accumulate in the hepatocyte over a period of time leading to FATTY LIVER!! A case stem based question on the above concept. You can leave your answer as a comment below.
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