Fedosov Sergey N
Protein Chemistry Laboratory, Department of Molecular Biology, University of Aarhus, Aarhus, Denmark,
Subcell Biochem. 2012;56:347-67. doi: 10.1007/978-94-007-2199-9_18.
Minute doses of a complex cofactor cobalamin (Cbl, vitamin B12) are essential for metabolism. The nutritional chain for humans includes: (1) production of Cbl by bacteria in the intestinal tract of herbivores; (2) accumulation of the absorbed Cbl in animal tissues; (3) consumption of food of animal origin. Most biological sources contain both Cbl and its analogues, i.e. Cbl-resembling compounds physiologically inactive in animal cells. Selective assimilation of the true vitamin requires an interplay between three transporting proteins - haptocorrin (HC), intrinsic factor (IF), transcobalamin (TC) - and several receptors. HC is present in many biological fluids, including gastric juice, where it assists in disposal of analogues. Gastric IF selectively binds dietary Cbl and enters the intestinal cells via receptor-mediated endocytosis. Absorbed Cbl is transmitted to TC and delivered to the tissues with blood flow. The complex transport system guarantees a very efficient uptake of the vitamin, but failure at any link causes Cbl-deficiency. Early detection of a negative B12 balance is highly desirable to prevent irreversible neurological damages, anaemia and death in aggravated cases. The review focuses on the molecular mechanisms of cobalamin transport with emphasis on interaction of corrinoids with the specific proteins and protein-receptor recognition. The last section briefly describes practical aspects of recent basic research concerning early detection of B12-related disorders, medical application of Cbl-conjugates, and purification of corrinoids from biological samples.
微量的复合辅因子钴胺素（Cbl，维生素B12）对新陈代谢至关重要。人类的营养链包括：（1）食草动物肠道中的细菌产生Cbl；（2）吸收的Cbl在动物组织中积累；（3）食用动物源性食物。大多数生物来源都同时含有Cbl及其类似物，即在动物细胞中生理上无活性的类Cbl化合物。真正的维生素的选择性同化需要三种转运蛋白——运钴胺素蛋白（HC）、内因子（IF）、转钴胺素（TC）以及几种受体之间的相互作用。HC存在于许多生物体液中，包括胃液，它在其中协助处理类似物。胃内因子选择性结合膳食中的Cbl，并通过受体介导的内吞作用进入肠道细胞。吸收的Cbl被传递给TC，并随着血流输送到组织中。这种复杂的转运系统保证了维生素的高效摄取，但任何一个环节出现故障都会导致Cbl缺乏。尽早发现B12负平衡非常有必要，以防止在病情加重时出现不可逆转的神经损伤、贫血和死亡。这篇综述重点关注钴胺素转运的分子机制，尤其强调类咕啉与特定蛋白质的相互作用以及蛋白质-受体识别。最后一部分简要描述了近期基础研究在B12相关疾病早期检测、Cbl偶联物的医学应用以及从生物样品中纯化类咕啉方面的实际情况。
