Etfa, an electron transfer flavoprotein, is involved in fatty acid, amino acid, and choline metabolism. It functions as part of the multiple acyl-CoA dehydrogenase pathway, a key metabolic route. Genetic studies on Etfa can provide insights into related metabolic disorders [1,2].

A novel homozygous promoter variant in Etfa (c.-85G > A) was identified in a patient with multiple acyl-CoA dehydrogenase deficiency (MADD) through whole genome sequencing. This variant led to decreased Etfa protein expression in lymphoblasts and reduced promoter activity, suggesting a potential late-onset form of MADD (Type III) [1]. In mice, Acox2 knockout led to downregulated non-histone lysine crotonylation levels in the liver, and Etfa was among the enzymes with downregulated non-histone Kcr sites, indicating its role in hepatic metabolic homeostasis [2].

In conclusion, Etfa is crucial for normal metabolism, especially in fatty acid, amino acid, and choline metabolic pathways. Studies on Etfa, such as the identification of its promoter variants in MADD patients and its involvement in hepatic metabolic regulation in mice, contribute to understanding metabolic disorders and hepatic function.

References:

1. Prasun, Pankaj, Evans, Anthony, Cork, Emalyn, Houten, Sander M, Webb, Bryn D. 2022. A novel deleterious ETFA promoter variant causative of multiple acyl-CoA dehydrogenase deficiency. In American journal of medical genetics. Part A, 191, 1089-1093. doi:10.1002/ajmg.a.63104. https://pubmed.ncbi.nlm.nih.gov/36579410/

2. Zhang, Yuan, Chen, Yuling, Zhang, Zhao, Zhao, Jianyuan, Zhou, Xiangyu. 2022. Acox2 is a regulator of lysine crotonylation that mediates hepatic metabolic homeostasis in mice. In Cell death & disease, 13, 279. doi:10.1038/s41419-022-04725-9. https://pubmed.ncbi.nlm.nih.gov/35351852/