GtoPdb v.2023.1中的神经酰胺周转

Anthony H. Futerman
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摘要

神经酰胺是在内质网合成的鞘磷脂家族,介导细胞凋亡、自噬和衰老等应激反应,丝氨酸棕榈酰基转移酶生成3-酮鞘氨酸,其还原为二氢鞘氨酸。n -酰化允许形成二氢神经酰胺,其随后被还原成神经酰胺。一旦合成,神经酰胺从内质网转运到高尔基体,并与神经酰胺转移蛋白CERT (COL4A3BP, Q9Y5P4)结合。神经酰胺可以通过多种途径代谢,确保其细胞水平的严格调节。添加磷脂胆碱生成鞘磷脂,而添加碳水化合物形成葡萄糖或半乳糖神经酰胺。神经酰胺酶从神经酰胺或二氢神经酰胺重新生成鞘氨醇或鞘氨酸。神经酰胺的磷酸化产生磷酸神经酰胺。鞘脂代谢途径中许多酶的准确动力学参数的测定由于底物的亲脂性而变得复杂。
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Ceramide turnover in GtoPdb v.2023.1
Ceramides are a family of sphingophospholipids synthesized in the endoplasmic reticulum, which mediate cell stress responses, including apoptosis, autophagy and senescence, Serine palmitoyltransferase generates 3-ketosphinganine, which is reduced to dihydrosphingosine. N-Acylation allows the formation of dihydroceramides, which are subsequently reduced to form ceramides. Once synthesized, ceramides are trafficked from the ER to the Golgi bound to the ceramide transfer protein, CERT (COL4A3BP, Q9Y5P4). Ceramide can be metabolized via multiple routes, ensuring tight regulation of its cellular levels. Addition of phosphocholine generates sphingomyelin while carbohydrate is added to form glucosyl- or galactosylceramides. Ceramidase re-forms sphingosine or sphinganine from ceramide or dihydroceramide. Phosphorylation of ceramide generates ceramide phosphate. The determination of accurate kinetic parameters for many of the enzymes in the sphingolipid metabolic pathway is complicated by the lipophilic nature of the substrates.
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