PS is fundamentally important for life. It is an essential building block for the cell membrane system that manages most life processes.⁶ Cell membranes are thin, continuous structures composed mainly of phospholipids (a lipid bilayer), into which are inserted myriad catalytic proteins. PS is an essential phospholipid for the membrane system, helping to create the physical–chemical milieu appropriate for optimal protein activity.^2,⁷

The PS molecule has a characteristic layout (Figure 113-1)—a head piece, a middle piece, and two tail pieces (“tails”).^2,⁷ The head piece contains serine attached to a phosphoryl group, has a net negative charge, and is positioned on the membrane’s inner (cytoplasmic) surface.⁷ The middle piece is a 3-carbon glyceryl sequence. The two tail pieces are constructed from fatty acids, extend deep into the membrane, and help maintain the semi-fluid membrane interior that the proteins require for their catalytic activity.²

FIGURE 113-1 Phosphatidylserine.

Biochemically, PS is not a single molecule but a family of molecules.^2,⁸ The head and middle pieces are standard, but each of the two tail groups can be constructed from many different fatty acids. Thus, there are as many PS molecules as there are fatty acid permutations. Further, all cells carry enzymes (“acylases”) that can detach one fatty acid tail and substitute it with another, depending on the need for membrane fluidity.⁸ In the brain’s highly active gray matter, the PS molecules on average carry more of the highly fluidizing ω-3 fatty acids; in contrast, PS in the white matter has less ω-3 and more saturated and mono-unsaturated (ω-9) fatty acid tails.⁸

Physiologic Roles

The presence of PS in cell membranes enables the brain’s electrical activity, the blood’s clotting properties, bone matrix formation, and the selective removal of dying cells from the tissues.^2,⁷ All these processes are based in cell membrane structure and function. At the cell membrane level, activities specifically linked to PS include⁸^–¹²:

• Energetics: Adenosine triphosphate (ATP) production by the mitochondria relies on phosphatidylethanolamine in their membranes, generated exclusively from PS.⁸

• Membrane/cell stabilization: PS binds with structural proteins to stabilize the cell’s outer membrane and overall cell shape.⁹

• Signal transduction: The conversion of external signals to internal cell transformations, which often requires protein kinase C, a PS-dependent protein.¹⁰

• Secretion: The presence of PS enables membrane vesicles within the cell to fuse with the outer cell membrane and release their contents.¹¹

• Apoptosis: A cell that is dying allows its PS to “flip” to the outer (external) face of the cell membrane. This serves as a “suicide” signal for immune cells to recycle that cell.¹²

Pharmacology

The pharmacology of PS is consonant with its diverse actions in cell membranes.^2,^13,¹⁴ In animal studies, PS enhanced the activities of at least nine major transmitter systems (reviewed in Kidd²). In animal and human studies, PS enhanced stress management via the hypothalamic-pituitary-adrenal (HPA) axis,¹⁴ as well as the diurnal hormone secretory rhythms of the pituitary gland.¹⁵

Other animal findings indicated PS has an overall trophic (restorative) effect in the brain. Feeding PS to aging rats significantly slowed the usual age-related decline of forebrain cholinergic synapses ¹⁶ and of nerve cells and their dendritic densities in the hippocampus.^17,¹⁸ Also in aging rats, PS by mouth significantly slowed the age-associated decline of receptors for nerve growth factor, a protein factor that stimulates brain circuit maintenance and renewal.¹⁸

Consistent with its importance for mitochondrial function, PS supports brain energetics. A single-photon emission computed tomographic imaging study of dementia patients found that orally administered PS improved energy production and utilization throughout the brain.¹⁹