One disadvantage of phosphatidic acid is that it is a negative
ion (anion), and needs nearby positive ions (cations) to neutralize
its negative charge. This problem can be avoided, while preserving
the charged polar character of the head of the molecule, if the
phosphate group is esterified again with an alcohol that carries
its own positive charge. Such a molecule is ethanolamine, HO-CH2CH2-NH2,
which at neutral pH exists in the ionized form: HO-CH2CH2-NH3+.
This second esterification produces phosphatidyl ethanolamine, or
cephalin (shown here). The cephalin molecule is half hydrophobic
and half charged polar, yet electrostatically neutral because it
carries its counter ion with it.
Cephalin has one flaw. As a primary amine, it can lose a proton
and its positive charge under basic conditions and revert to a negatively
charged molecule, such as phosphatidic acid. The ingenious solution
that actually is used in membranes is to substitute for ethanolamine
a quaternary ammonium ion that cannot deprotonate and lose its positive
charge. The main lipid component in biological membranes is phosphatidyl
choline, or lecithin (right). In lecithin the phosphate group is
esterified with the quaternary ammonium compound choline, HO-CH2CH2-N+(CH3)3,
which is identical to ethanolamine except for the three methyl groups
on the nitrogen. Lecithin cannot lose its positive charge and therefore
must remain a neutral molecule overall. The actual shape of a lecithin
molecule is indicated by the space-filling model shown by the right
button.