Enoyl CoA Isomerase - Medical Relevance

Medical Relevance

In humans, defects in the beta-oxidation mechanism result in hypoketotic hyperglycemia, a symptom of starvation, due to the inefficient utilization of fatty acids as a primary source of energy. The metabolic disease was found to be on a genetic level: rats without the genes for enoyl-CoA isomerase also displayed high blood glucose level. Moreover, a biological marker for this condition may have been identified as the urine of these rats included high concentrations of medium chain unsaturated dicarboxylic acids, a condition called dicarboxylic aciduria.

More recent studies link hepatitis C virus (HCV) infection to defects in fatty acid degradation, specifically, to that in enoyl-CoA isomerase. HCV is the leading cause of chronic hepatitis, cirrhosis, and liver cancer, and more than 180 million people are affected globally. Due to the prolonged latency of the virus and no existing cures to rid the virus specifically, HCV is a serious problem that is causing more deaths than HIV/AIDS in the United States, but its threat still do not receive adequate attention. The need for a HCV-specific treatment is essential, and according to John Ward, the director of the CDC Hepatitis Division, it can save up to 120,000 lives.

According to protein profiling in the human liver biopsies of HCV patients, a correlation was initially discovered between dysfunctional mitochondrial processes, which include beta-oxidation, and HCV. As a matter of fact, lipids play an important role in the replication cycle of HCV, and in the "in vivo" samples from HCV patients, many lipids were found in abundance to aid HCV in virus uptake, RNA replication, and secretion from host cells. Enzymes that regulate fatty acid metabolism, including enoyl-CoA isomerase, were also similarly upregulated. Gene silencing techniques revealed that enoyl-CoA isomerase is essential in HCV RNA replication, and opened ways to stop HCV infection on an intracellular level.