コリンおよびコリントランスポーターの生理機能(<特集>ビタミン・バイオファクターのトランスポーター[I])
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概要
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Choline is an organic cation that is crucial for the normal function of all cells. It is used as a precursor of acetylcholine, a methyl donor, and osmolyte betaine, and plays an important role in the biosynthesis of phosphatidylcholine and sphingomyelin. Choline is consumed in the diet and insufficient intake may cause choline deficiency, especially under conditions that require large amounts of choline, such as pregnancy, breast-feeding and parenteral nutrition. Choline deficiency affects the expression of genes involved in cell proliferation, differentiation, and apoptosis, and it is associated with liver dysfunction and cancer. Therefore, the study of choline transport and the characteristics of choline transporters are of central importance to understand the mechanisms that underlie membrane integrity and cell signaling. The choline transport system has been categorized into three transporter families. They include (I) polyspecific organic cation transporters (OCTs) with low affinity for choline, (II) high-affinity choline transporter 1 (CHT1), and (III) intermediate-affinity choline transporter-like proteins (CTLs). CHT1 and CTL1 but not OCT transporters are selectively inhibited with hemicholinium-3 (HC-3) and essentially display characteristics of specialized transporters for targeted choline metabolism. CHT1 is thought to play an important role in cholinergic neurons and is also expressed by subpopulations of non-neuronal cholinergic cells. CHT1 is a Na^+-dependent co-transporter that is highly sensitive to the choline analogue, HC-3, and is thought to be part of the rate-limiting step in acetylcholine synthesis. As an organic cation, choline is known to be a substrate for carriers of OCTs. To date, three different OCTs (OCT1-3) have been cloned and they function through Na^+-independent uptake mechanism. OCT1 and OCT2 accept choline as a substrate with comparatively low affinity. However, OCT3 does not recognize choline as a substrate. CTL family are comprised of the five genes, CTL1-5, with CTL1 being the main member of the family. CTL1 is a Na^+-independent, intermediate-affinity transporter of choline that can be completely inhibited by a high concentration of HC-3. They are expressed in different organisms and cell types, and this implies its importance for choline transport for a broader purpose, such as phospholipid synthesis. The function of CTL2-5 is still not precisely known at the molecular level. In this review, the functional expression and physiological role of choline transporters is further discussed.
- 2010-08-25
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