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肠道左旋肉碱转运的功能特性

Functional characterization of intestinal L-carnitine transport.

作者信息

Durán J M, Peral M J, Calonge M L, Ilundáin A A

机构信息

Depto. Fisiología y Biología Animal, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain.

出版信息

J Membr Biol. 2002 Jan 1;185(1):65-74. doi: 10.1007/s00232-001-0110-5. Epub 2002 Feb 5.

DOI:10.1007/s00232-001-0110-5
PMID:11891565
Abstract

The carnitine transporter OCTN2 is responsible for the renal reabsorption of filtered L-carnitine. However, there is controversy regarding the intestinal L-carnitine transport mechanism(s). In this study, the characteristics of L-carnitine transport in both, isolated chicken enterocytes and brush-border membrane vesicles (BBMV) were studied. In situ hybridization was also performed in chicken small intestine. Chicken enterocytes maintain a steady-state L-carnitine gradient of 5 to 1 and 90% of the transported L-carnitine remains in a readily diffusive form. After 5 min, L-Carnitine uptake into BBMV overshot the equilibrium value by a factor of 2.5. Concentrative L-carnitine transport is Na+-, membrane voltage-and pH-dependent, has a high affinity for L-carnitine (Km 26 - 31 microM ) and a 1:1 Na+: L-carnitine stoichiometry. L-Carnitine uptake into either enterocytes or BBMV was inhibited by excess amount of cold L-carnitine > D-carnitine = acetyl-L-carnitine = gamma-butyrobetaine > palmitoyl-L-carnitine > betaine > TEA, whereas alanine, histidine, GABA or choline were without significant effect. In situ hybridization studies revealed that only the cells lining the intestinal villus expressed OCTN2 mRNA. This is the first demonstration of the operation of a Na+/L-carnitine cotransport system in the apical membrane of enterocytes. This transporter has properties similar to those of OCTN2.

摘要

肉碱转运体OCTN2负责肾脏对滤过的左旋肉碱的重吸收。然而,关于肠道左旋肉碱转运机制存在争议。在本研究中,对分离的鸡肠上皮细胞和刷状缘膜囊泡(BBMV)中左旋肉碱的转运特性进行了研究。还在鸡小肠中进行了原位杂交。鸡肠上皮细胞维持5比1的稳态左旋肉碱梯度,且90%的转运左旋肉碱保持易于扩散的形式。5分钟后,BBMV对左旋肉碱的摄取超过平衡值2.5倍。浓缩性左旋肉碱转运是依赖钠离子、膜电位和pH的,对左旋肉碱具有高亲和力(Km为26 - 31微摩尔),且钠离子与左旋肉碱的化学计量比为1:1。过量的冷左旋肉碱>D - 肉碱 = 乙酰左旋肉碱 = γ - 丁酸甜菜碱>棕榈酰左旋肉碱>甜菜碱>四乙铵抑制了左旋肉碱进入肠上皮细胞或BBMV,而丙氨酸、组氨酸、γ - 氨基丁酸或胆碱则无显著影响。原位杂交研究表明,只有肠绒毛内衬细胞表达OCTN2 mRNA。这是首次证明肠上皮细胞顶端膜中存在钠离子/左旋肉碱共转运系统。该转运体具有与OCTN2相似的特性。

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