PREFERENTIAL DECARBOXYLATION OF HYDROPHILIC PHOSPHATIDYLSERINE SPECIES IN CULTURED-CELLS - IMPLICATIONS OF THE MECHANISM OF TRANSPORT TO MITOCHONDRIA AND CELLULAR AMINOPHOSPHOLIPID SPECIES COMPOSITIONS
L. Heikinheimo et P. Somerharju, PREFERENTIAL DECARBOXYLATION OF HYDROPHILIC PHOSPHATIDYLSERINE SPECIES IN CULTURED-CELLS - IMPLICATIONS OF THE MECHANISM OF TRANSPORT TO MITOCHONDRIA AND CELLULAR AMINOPHOSPHOLIPID SPECIES COMPOSITIONS, The Journal of biological chemistry, 273(6), 1998, pp. 3327-3335
In baby hamster kidney and other cultured cells the majority of phosph
atidylethanolamine (PE) is synthesized from phosphatidylserine (PS) in
a process which involves transport of PS from the endoplasmic reticul
um to mitochondria and decarboxylation therein by PS decarboxylase. To
study the mechanism of this transport process, we first determined th
e 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 P
S, suggesting that hydrophilic PS species may be more readily transpor
ted to mitochondria than the hydrophobic ones. To study this, me compa
red 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 d
etermined by reverse phase high performance liquid chromatography and
liquid scintillation counting. The hydrophilic PE species contained re
latively much more H-3 label than those of PS, which indicates that th
ey are more readily decarboxylated than the hydrophobic ones. Control
experiments showed that differences in [H-3]PS and -PE molecular speci
es profiles are not due to (i) incorporation of H-3 label to some PE s
pecies via alternative pathways, (ii) differences in degradation or re
modeling among species, or (iii) selective decarboxylation of PS molec
ular species by the enzyme. Therefore, hydrophilic PS species are inde
ed decarboxylated faster than the hydrophobic ones. The rate of decarb
oxylation decreased systematically with hydrophobicity, strongly sugge
sting that formation of so called activated monomers, i.e. lipid molec
ules perpendicularly displaced from the membrane (Jones, J. D., and Th
ompson, T. E. (1990) Biochemistry 29, 1593-1600), is the rate-limiting
step in the transport of PS from the endoplasmic reticulum to mitocho
ndria. The formation of activated monomers and thus the rate of transf
er 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 t
hese cells are much more abundant in PE as compared with PS, its immed
iate precursor.