Phosphatidate phosphatase

Phosphatidate can then be converted into an activated form, CDP-diacylglycerol by liberation of a pyrophosphate from a CTP molecule, or into cardiolipin.

Furthermore, because both phosphatidate and diacylglycerol function as secondary messengers, phosphatidate phosphatase is able to exert extensive and intricate control of lipid metabolism far beyond its local effect on phopshatidate and diacylglycerol concentrations and the resulting effect on the direction of lipid flux as outlined above.

Each of the 3 Lipin proteins found in mammals—Lipin1, Lipin2, and Lipin3—has unique tissue expression motifs and distinct physiological functions.

For example, Lipin1 is induced by glucocorticoids during adipocyte differentiation as well as in cells that are experiencing proliferation of the endoplasmic reticulum (ER).

[11] Type II phosphatidate phosphatases are transmembrane enzymes found mainly in the plasma membrane.

While all three catalyze the reaction from PGP to PG, their amino acid sequences are dissimilar and it is predicted that their active sites open to different sides of the cytoplasmic membrane.

The enzyme active site contains a catalytic triad Asp-211, His-207, and His-163 that establishes a charge relay system.

[14]Human genes that encode phosphatidate phosphatases include: Lipin-1 deficiency in mice results in lipodystrophy, insulin resistance, and neuropathy.

In humans, variations in Lipin-1 expression levels can result in insulin sensitivity, hypertension, and risk for metabolic syndrome.

Reactants and products of the reaction catalyzed by the enzyme phosphatidate phosphatase, and thus also those of the reverse reaction, which is catalyzed by the enzyme diacylglycerol kinase .
Dephosphorylation of phosphatidylglycerol phosphate (PGP) to form PG (phosphatidylglycerol). This reaction is catalyzed by PgpB, a bacterial integral membrane lipid phosphate phosphatase.
PgpB (PDBe: 5jwy) cartoon with ribbons. Made in MacPyMOL.