Flavin adenine dinucleotide

Flavin adenine dinucleotide (FAD) is an important redox cofactor that is widely involved in cellular energy metabolism and electron transfer processes^{[1, 2]}. Flavin adenine dinucleotide is composed of riboflavin (vitamin B2) and adenosine monophosphate (AMP) connected by a phosphate group. It can be reversibly converted between FAD (oxidized state) and FADH₂ (reduced state) and participates in the double electron transfer reaction^[3]. Flavin adenine dinucleotide can cause vasodilation in the rat mesenteric and hindlimb vascular beds^[4].

In vitro, treatment of HeLa cells with Flavin adenine dinucleotide (12.5μM) under blue light irradiation for 2h significantly increased the generation of intracellular reactive oxygen species (ROS)^[5].

In vivo, Flavin adenine dinucleotide (0.1mg/kg) was intraperitoneally injected into spontaneously hypertensive (SHR) rats for 8 weeks, which improved vascular remodeling in the rats. The arrangement of aortic vascular fibers in the hypertensive state was improved, the medial layer was thinned, and the elastic fiber structure of the intima returned to normal^[6]. Flavin adenine dinucleotide (2mg/kg) was administered intravenously to treat dogs with chlorpromazine (CPZ)-induced ventricular arrhythmias and significantly offset the CPZ-induced decrease in ventricular fibrillation threshold (VFT)^[7].

References:
[1] Barile M, Giancaspero T A, Leone P, et al. Riboflavin transport and metabolism in humans[J]. Journal of inherited metabolic disease, 2016, 39(4): 545-557.
[2] Palmieri F, Monné M, Fiermonte G, et al. Mitochondrial transport and metabolism of the vitamin B‐derived cofactors thiamine pyrophosphate, coenzyme A, FAD and NAD+, and related diseases: A review[J]. IUBMB life, 2022, 74(7): 592-617.
[3] Foroutannejad S. Single-molecule Analysis of the Role of Flavin Adenine Dinulcleotide in the Conformational Landscapes of Drosophila Cryptochrome[M]. Georgetown University, 2020.
[4] Hashmi-Hill M P, Sandock K, Bates J N, et al. Flavin adenine dinucleotide may release preformed stores of nitrosyl factors from the vascular endothelium of conscious rats[J]. Journal of cardiovascular pharmacology, 2007, 50(2): 142-154.
[5] Yang M Y, Chang C J, Chen L Y. Blue light induced reactive oxygen species from flavin mononucleotide and flavin adenine dinucleotide on lethality of HeLa cells[J]. Journal of Photochemistry and Photobiology B: Biology, 2017, 173: 325-332.
[6] Zhong X, Ma Z, Su Y, et al. Flavin adenine dinucleotide ameliorates hypertensive vascular remodeling via activating short chain acyl-CoA dehydrogenase[J]. Life sciences, 2020, 258: 118156.
[7] SUGWYAMA S, Ozawa T. Protection of chlorpromazine-induced arrhythmia by flavin-adenine-dinucleotide in canine heart[J]. Japanese Heart Journal, 1979, 20(5): 657-665.

Flavin adenine dinucleotide（黄素腺嘌呤二核苷酸，FAD）是一种重要的氧化还原辅因子，广泛参与细胞的能量代谢和电子传递过程^{[1, 2]}。Flavin adenine dinucleotide由核黄素（维生素B2）、腺苷一磷酸（AMP）通过磷酸基团连接而成，能够在FAD（氧化态）和FADH₂（还原态）之间可逆转化，参与双电子转移反应^[3]。Flavin adenine dinucleotide能够引起大鼠肠系膜和后肢血管床中的血管舒张^[4]。

在体外，Flavin adenine dinucleotide（12.5μM）处理蓝光照射条件下的HeLa细胞2h，显著增加了细胞内活性氧（ROS）的生成^[5]。

在体内，Flavin adenine dinucleotide（0.1mg/kg）通过腹腔注射治疗自发性高血压（SHR）大鼠8周，改善了大鼠的血管重塑，高血压状态下的主动脉血管纤维排列改善，中膜变薄，内膜弹性纤维结构恢复正常^[6]。Flavin adenine dinucleotide（2mg/kg）通过静脉注射治疗氯丙嗪（CPZ）诱发室性心律失常的犬，显著抵消了氯丙嗪引起的室颤阈值（VFT）降低^[7]。