Phosphatidic acid

Phosphatidic acids (PAs) are the acid forms of phosphatidates, a part of common phospholipids, major constituents of cell membranes. Phosphatidic acids are the simplest diacyl-glycerophospholipids.

Phosphatidic acid consists of a glycerol backbone, with, in general, a saturated fatty acid bonded to carbon-1, an unsaturated fatty acid bonded to carbon-2, and a phosphate group bonded to carbon-3.

Besides de novo synthesis, PA can be formed in three ways:

PA is degraded by conversion into DAG by lipid phosphate phosphohydrolases (LPPs) or into lyso-PA by phospholipase A (PLA).

The role of PA in the cell can be divided into three categories:

The first three roles are not mutually exclusive. For example, PA may be involved in vesicle formation by promoting membrane curvature and by recruiting the proteins to carry out the much more energetically unfavourable task of neck formation and pinching.

PA is a vital cell lipid that acts as a biosynthetic precursor for the formation (directly or indirectly) of all acylglycerol lipids in the cell.

In mammalian and yeast cells, two different pathways are known for the de novo synthesis of PA, the glycerol 3-phosphate pathway or the dihydroxyacetone phosphate pathway. In bacteria, only the former pathway is present, and mutations that block this pathway are lethal, demonstrating the importance of PA. In mammalian and yeast cells, where the enzymes in these pathways are redundant, mutation of any one enzyme is not lethal. However, it is worth noting that in vitro, the various acyltransferases exhibit different substrate specificities with respect to the acyl-CoAs that are incorporated into PA. Different acyltransferases also have different intracellular distributions, such as the endoplasmic reticulum (ER), the or peroxisomes, and local concentrations of activated fatty acids. This suggests that the various acyltransferases present in mammalian and yeast cells may be responsible for producing different pools of PA.

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