# Inositol-Exchange Activity in Human Primordial Placenta

## TL;DR

This study identifies and characterizes the inositol exchange enzyme activity in human primordial placenta, revealing a new pathway for inositol synthesis that could have therapeutic implications for pregnancy.

## Contribution

The study is the first to document inositol exchange enzyme activity in human placenta and describe its physiological properties.

## Key findings

- Inositol exchange enzyme activity was detected and characterized in human primordial placenta for the first time.
- Phosphatidylinositol synthase activity was optimal at 0.5–2.0 mM Mn2+ and increased with Mg2+ up to 100 mM.
- Stable GTP analog increased [3H]inositol incorporation into PI by 57%, suggesting a novel regulatory mechanism.

## Abstract

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 Mn2+ and Mg2+ 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 Mn2+ concentration, but higher concentrations inhibit enzyme activity. In the presence of Mg2+, 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 Mn2+ 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.