Biochemistry and Fatty Liver Disease

Question

People who eat a large amount of fattening foods often develop fatty liver disease. People with fatty liver disease often have large numbers of small droplets of triglycerides throughout their livers. Having this disorder increases the likelihood of developing a large variety of liver diseases such as hepatitis, liver cancer, or cirrhosis of the liver. Why might fatty liver disease increase the risk for these conditions?

Alcoholics, regardless of their fat intake, often develop fatty liver disease. Here it is called alcoholic fatty liver disease. When alcohol is consumed, it is oxidized to acetaldehyde and then to acetic acid by NAD+. The acetic acid is mostly excreted through the urine or converted to acetyl CoA. The side products of this reaction stimulate fatty acid synthesis.

What side products are produced by alcohol oxidation?

Why do these side products cause the synthesis of fatty acids?

Finally, another cause of fatty liver disease is, somewhat non-intuitively, rapid weight loss. Given the livers many functions related to maintenance of homeostasis, why do you think this occurs?

Answer 1

1. What side products are produced by alcohol oxidation?
2. The first step involved in alcohol oxidation is the production of ethanal, NADH, and hydrogen ions: CH₃CH₂OH + NAD⁺ –> CH₃CHO + NAHD + H⁺
3. The second step involved in alcohol oxidation is the breakdown of ethanal into acetic acid: CH₃CHO + NAHD + H₂O –> CH₃COOH + NADH + H⁺
4. The more ethanol (toxic) that is ingested, the greater amount of ethanal that must be broken down into acetic acid (harmless). One of the reasons ethanol is so toxic is because of it prevents peroxisome proliferator-activated receptor α from activating DNA sequences/starting chain reactions that help break down fatty acids.