Honsho Masanori, Fujiki Yukio
Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
FEBS Lett. 2017 Sep;591(18):2720-2729. doi: 10.1002/1873-3468.12743. Epub 2017 Jul 28.
Plasmalogens, mostly ethanolamine-containing alkenyl ether phospholipids, are a major subclass of glycerophospholipids. Plasmalogen synthesis is initiated in peroxisomes and completed in the endoplasmic reticulum. The absence of plasmalogens in several organs of peroxisome biogenesis-defective patients suggests that the de novo synthesis of plasmalogens plays a pivotal role in its homeostasis in tissues. Plasmalogen synthesis is regulated by modulating the stability of fatty acyl-CoA reductase 1 on peroxisomal membranes, a rate-limiting enzyme in plasmalogen synthesis, by sensing plasmalogens in the inner leaflet of plasma membranes. Dysregulation of plasmalogen homeostasis impairs cholesterol biosynthesis by altering the stability of squalene monooxygenase, a key enzyme in cholesterol biosynthesis, implying physiological consequences of plasmalogen homeostasis with respect to cholesterol metabolism in cells, as well as in organs such as the liver.
缩醛磷脂主要是含乙醇胺的烯基醚磷脂，是甘油磷脂的一个主要亚类。缩醛磷脂的合成始于过氧化物酶体，在内质网中完成。过氧化物酶体生物发生缺陷患者的多个器官中缺乏缩醛磷脂，这表明缩醛磷脂的从头合成在其组织稳态中起关键作用。通过感知质膜内小叶中的缩醛磷脂，调节过氧化物酶体膜上脂肪酸酰基辅酶A还原酶1（缩醛磷脂合成中的限速酶）的稳定性，从而调节缩醛磷脂的合成。缩醛磷脂稳态失调会通过改变角鲨烯单加氧酶（胆固醇生物合成中的关键酶）的稳定性来损害胆固醇生物合成，这意味着缩醛磷脂稳态在细胞以及肝脏等器官的胆固醇代谢方面具有生理影响。
