Phosphatidylserine transport

REGULATION OF PHOSPHATIDYLSERINE BIOSYNTHESIS AND TRANSPORT IN MAMMALIAN CELLS... 

Emoto, K., Kuge, O., Nishijima, M., and Umeda, M., 1999, Isolation ofa Chinese hamster ovary ceh mutant defective in intramitochondrial transport of phosphatidylserine. Proc. Natl. Acad. Sci. USA, 96 12400-12405. 

Many of the proteins of membranes are enzymes. For example, the entire electron transport system of mitochondria (Chapter 18) is embedded in membranes and a number of highly lipid-soluble enzymes have been isolated. Examples are phosphatidylseiine decarboxylase, which converts phosphatidylserine to phosphatidylethanolamine in biosynthesis of the latter, and isoprenoid alcohol phosphokinase, which participates in bacterial cell wall synthesis (Chapter 20). A number of ectoenzymes are present predominantly on the outsides of cell membranes.329 Enzymes such as phospholipases (Chapter 12), which are present on membrane surfaces, often are relatively inactive when removed from the lipid environment but are active in the presence of phospholipid bilay-ers.330 33 The distribution of lipid chain lengths as well as the cholesterol content of the membrane can affect enzymatic activities.332... 

Fig. 5.17 Permeability coefficients, P°, for doxorubicin transport across model membranes composed of different phospholipids. PC, phosphatidylcholine PE, phos-phatidylethanolamine PS, phosphatidylserine SM, sphingomyelin. (Reprinted from Fig. 3 of ref. 115 with permission from the American Chemical Society.)...

Nucleation of calcium phosphate precipitation within the matrix vesicles is mediated by phosphatidylserine, which comprises about 8% of the phospholipids of the inner cytosolic membrane surface (Fig. 9.5a). Calbindin in the vesicle (Fig. 9.5b) may also contribute. Rapid mineral growth within the vesicle keeps the concentration of dissolved calcium and inorganic phosphate ions so low that additional Ca2+ and Pi ions spontaneously enter from the extracellular fluid via their respective transporters. Attached type II and type X collagens from cartilage in the growth plate enhance calcium ion transport and calcification during endochondral ossification (Fig. 9.5b). 

Osteoblasts secrete osteoid, a matrix rich in type I collagen fibers and vesicles. Precipitation of calcium phosphate is inhibited by a high concentration of pyrophosphate in stromal interstitial fluids, and a high concentration also of albumin and citrate in blood plasma. Pyrophosphate is derived from (1) transport out of the cytosol, and (2) synthesis from nucleoside triphosphates in the stromal interstitial fluid that permeates the osteoid matrix. Precipitation occurs only when calcium and phosphate ions are taken up into vesicles whose inner membrane is composed of phosphatidylserine. The high concentration of calcium and phosphate ions in the vesicle is mediated by annexin and type HI Pi Na-dependent transporters. This overwhelms the pyrophosphate and nucleation occurs. As the precipitate grows and ruptures the membrane, tissue-nonspecific alkaline phosphatase is activated to remove pyrophosphate from the osteoid matrix fluid so that calcium phosphate precipitates around phosphorylated serine residues within the collagen fibers. 

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