Determinants of the selection of phosphatidylcholine molecular species for secretion into bile in the rat

Abstract

Certain phosphatidylcholine (PC) molecular species appear to be secreted into bile preferentially, but the mechanism for this selection remains obscure. We used multivariate analysis to examine the relationship between PC structure and the odds of secretion for individual PC species secreted into bile. PC was isolated from Folch extracts of bile and liver from rats, and individual molecular species of PC were quantified with reverse-phase highperformance liquid chromatography (HPLC). The odds of secretion for a given PC species were quantified as the ratio of its mole % in bile/mole % in liver. Regression analysis indicated that the odds of secretion were significantly related to length of both the sn-1 and sn-2 acyl chains (P F .0001 for both) and to relative hydrophobicity as determined by reverse-phase HPLC (P F .0001). In addition, the relationship between odds of secretion and sn-1 chain length was best described by a parabolic function. Considered together, these characteristics accounted for 88% of the observed differences in odds of secretion. This relationship between PC structure and odds of secretion was strikingly similar to the relationship between PC structure and affinity for bovine PC transfer protein. When multivariate models were used to predict both the odds of secretion and the affinity for PC transfer protein for a set of biologically plausible PC species, there was a linear relationship between the two. The likelihood of a given PC species being secreted into bile can be related to the structural characteristics of the acyl chains without having to postulate the existence of a special pool of PC destined for biliary secretion. Second, the structural characteristics that dictate selection of PC species for secretion into bile are similar to those that determine binding affinity for PC transfer protein, suggesting that the likelihood of a PC being secreted into bile is, in fact, closely related to its binding affinity for PC transfer protein (PC-TP). (HEPATOLOGY 1998;28:631-637.)There is abundant evidence that the biliary secretion of bile salts, phospholipids, and cholesterol are intimately linked, [1][2][3]

The Phosphoprotein StarD10 Is Overexpressed in Breast Cancer and Cooperates with ErbB Receptors in Cellular Transformation

“…Both StarD10 and Pctp are particularly abundant in the liver, where they may be involved in export of lipids into bile (47,48). The presence of high levels of StarD10 in the lactating mammary gland suggests a potential physiological role in the functional differentiation of this organ.…”

Structure and function of phosphatidylcholine transfer protein (PC-TP)/StarD2

“…Based upon its accentuated expression in the liver and its high relative affinities for phosphatidylcholine molecular species that are secreted by the liver into bile [51,52], it was proposed that PC-TP might transport phosphatidylcholines from their site of synthesis in the smooth endoplasmic reticulum to the canalicular membrane of hepatocyte for secretion into bile [53,54]. In support of this possibility, in vitro studies revealed that bile salts at submicellar concentrations that might be present in hepatocytes markedly increased that activity of PC-TP [53].…”

Clofibrate-Induced Relocation of Phosphatidylcholine Transfer Protein to Mitochondria in Endothelial Cells

“…Although extensive research has been done on the biophysical properties of this protein, little is known about the function of this protein in vivo. Possible physiological functions, among which is a role in bile secretion [4,5], have recently been refuted by van Helvoort et al [3]. In that study, PC-TP null mice failed to give a phenotype.…”