Department of Obstetrics and Gynecology, Semmelweis University, 1082 Budapest, Hungary.
Institute of Biochemistry and Molecular Biology, Semmelweis University, 1082 Budapest, Hungary.
Int J Mol Sci. 2024 Mar 19;25(6):3436. doi: 10.3390/ijms25063436.
Human placenta is an intensively growing tissue. Phosphatidylinositol (PI) and its derivatives are part of the signaling pathway in the regulation of trophoblast cell differentiation. There are two different enzymes that take part in the direct PI synthesis: phosphatidylinositol synthase (PIS) and inositol exchange enzyme (IE). The presence of PIS is known in the human placenta, but IE activity has not been documented before. In our study, we describe the physiological properties of the two enzymes in vitro. PIS and IE were studied in different Mn and Mg concentrations that enabled us to separate the individual enzyme activities. Enzyme activity was measured by incorporation of 3[H]inositol in human primordial placenta tissue or microsomes. Optimal PIS activity was achieved between 0.5 and 2.0 mM Mn concentration, but higher concentrations inhibit enzyme activity. In the presence of Mg, the enzyme activity increases continuously up to a concentration of 100 mM. PIS was inhibited by nucleoside di- and tri-phosphates. PI production increases between 0.1 and 10 mM Mn concentration. The incorporation of [3H]inositol into PI increased by 57% when adding stabile GTP analog. The described novel pathway of inositol synthesis may provide an additional therapeutic approach of inositol supplementation before and during pregnancy.
人类胎盘是一种快速生长的组织。磷脂酰肌醇（PI）及其衍生物是调节滋养细胞分化的信号通路的一部分。有两种不同的酶参与直接的 PI 合成：磷脂酰肌醇合酶（PIS）和肌醇交换酶（IE）。人胎盘中有 PIS 的存在，但 IE 活性以前没有记录。在我们的研究中，我们描述了两种酶在体外的生理特性。在不同的 Mn 和 Mg 浓度下研究了 PIS 和 IE，这使我们能够分离出单个酶的活性。通过将 3[H]肌醇掺入人原始胎盘组织或微粒体中来测量酶活性。最佳的 PIS 活性在 0.5 至 2.0 mM Mn 浓度之间，但较高浓度会抑制酶活性。在存在 Mg 的情况下，酶活性持续增加至 100 mM。PIS 被核苷二磷酸和三磷酸抑制。PI 的产生在 0.1 至 10 mM Mn 浓度之间增加。当添加稳定的 GTP 类似物时，[3H]肌醇掺入 PI 的量增加了 57%。描述的这种新的肌醇合成途径可能为妊娠前和妊娠期间补充肌醇提供了一种额外的治疗方法。
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