Preferential decarboxylation of hydrophilic phosphatidylserine species in cultured cells - Implications of the mechanism of transport to mitochondria and cellular aminophospholipid species compositions

In baby hamster kidney and other cultured cells the majority of phosphatidylethanolamine (PE) is synthesized from phosphatidylserine (PS) in a process which involves transport of PS from the endoplasmic reticulum to mitochondria and decarboxylation therein by PS decarboxylase. To study the mechanism of this transport process, we first determined the molecular species composition of PE and PS from baby hamster kidney and Chinese hamster ovary cells. Interestingly, the hydrophilic diacyl molecular species were found to be much more abundant in PE than in PS, suggesting that hydrophilic PS species may be more readily transported to mitochondria than the hydrophobic ones. To study this, me compared the rates of decarboxylation of different PS molecular species in these cells. The cells were pulse labeled with [H-3]serine whereafter the distribution of the labels among PS and PE molecular species was determined by reverse phase high performance liquid chromatography and liquid scintillation counting. The hydrophilic PE species contained relatively much more H-3 label than those of PS, which indicates that they are more readily decarboxylated than the hydrophobic ones. Control experiments showed that differences in [H-3]PS and -PE molecular species profiles are not due to (i) incorporation of H-3 label to some PE species via alternative pathways, (ii) differences in degradation or remodeling among species, or (iii) selective decarboxylation of PS molecular species by the enzyme. Therefore, hydrophilic PS species are indeed decarboxylated faster than the hydrophobic ones. The rate of decarboxylation decreased systematically with hydrophobicity, strongly suggesting that formation of so called activated monomers, i.e. lipid molecules perpendicularly displaced from the membrane (Jones, J. D., and Thompson, T. E. (1990) Biochemistry 29, 1593-1600), is the rate-limiting step in the transport of PS from the endoplasmic reticulum to mitochondria. The formation of activated monomers and thus the rate of transfer is probably greatly enhanced by frequent collisions between the two membranes which tend to be closely associated. The present data also provides a feasible explanation why hydrophilic molecular species in these cells are much more abundant in PE as compared with PS, its immediate precursor.