Prolonged ethanol consumption and subsequent metabolism ultimately leads to a condition referred to as steatohepatitis or more commonly, "fatty liver syndrome." Ethanol metabolism results in alteration in the activity of which of the following enzymes, one of the consequences of which is excess lipid deposition in the liver?

Question

Quizplus · Accepted Answer

Ethanol metabolism increases the NADH/NAD+ ratio, which enhances the activity of glycerol-3-phosphate dehydrogenase, leading to increased glycerol-3-phosphate and triglyceride synthesis, contributing to fatty liver.  The metabolism of ethanol by the liver leads to a large increase in NADH. This increase in NADH disrupts the normal processes of metabolic regulation such as hepatic gluconeogenesis, TCA cycle function, and fatty acid oxidation. Concomitant with reduced fatty acid oxidation is enhanced fatty acid synthesis and increased triglyceride production by the liver. In the mitochondria, the production of acetate from acetaldehyde leads to increased levels of acetylCoA. Since the increased generation of NADH also reduces the activity of the TCA cycle, the acetyl-CoA is diverted to fatty acid synthesis. The reduction in cytosolic NAD+ leads to reduced activity of glycerol-3-phosphate dehydrogenase (in the glycerol 3-phosphate to DHAP direction) resulting in increased levels of glycerol 3-phosphate, which is the backbone for the synthesis of the triglycerides. Both of these 2 events lead to fatty acid deposition in the liver leading to fatty liver syndrome and excessive levels of lipids in the blood, referred to as hyperlipidemia.

Prolonged Ethanol Consumption and Subsequent Metabolism Ultimately Leads to a Condition