Phosphoinositides (PIPn) in mammalian tissues are enriched in the stearoyl/arachidonoyl acyl chain species (“C38:4”), but its functional significance is unclear. We have used metabolic tracers (isotopologues of inositol, glucose and water) to study PIPn synthesis in cell lines in which this enrichment is preserved to differing relative extents. We show that PIs synthesised from glucose are initially enriched in shorter/more saturated acyl chains, but then rapidly remodelled towards the C38:4 species. PIs are also synthesised by a distinct ‘re-cycling pathway’, which utilises existing precursors and exhibits substantial selectivity for the synthesis of C38:4-PA and -PI. This re-cycling pathway is rapidly stimulated during receptor activation of phospholipase-C, both allowing the retention of the C38:4 backbone and the close coupling of PIPn consumption to its resynthesis, thus maintaining pool sizes. These results suggest that one property of the specific acyl chain composition of PIPn is that of a molecular code, to facilitate ‘metabolic channelling’ from PIP2 to PI via pools of intermediates (DG, PA and CDP-DG) common to other lipid metabolic pathways.

中文翻译：

---

酰基链选择耦合磷酸肌醇的消耗和合成

哺乳动物组织中的磷酸肌醇 (PIPn) 富含硬脂酰/花生四烯酰基酰基链种类（“C38:4”），但其功能意义尚不清楚。我们使用代谢示踪剂（肌醇、葡萄糖和水的同位素异数体）来研究细胞系中的 PIPn 合成，在这些细胞系中，这种富集被保存到不同的相对程度。我们表明，由葡萄糖合成的 PI 最初富含较短/更饱和的酰基链，但随后迅速重塑为 C38:4 物种。PI 也通过独特的“再循环途径”合成，该途径利用现有的前体并表现出对 C38:4-PA 和 -PI 合成的显着选择性。在磷脂酶-C 的受体激活过程中，这种再循环途径被迅速刺激，两者都允许 C38 的保留：4 骨干和 PIPn 消耗与其再合成的紧密耦合，从而保持池大小。这些结果表明，PIPn 的特定酰基链组成的一个特性是分子密码，以促进从 PIP2 到 PI 的“代谢通道”，通过其他脂质代谢途径共有的中间体池（DG、PA 和 CDP-DG） .