Herrmann Wolfgang, Obeid Rima
Department of Clinical Chemistry and Laboratory Medicine, University of Saarland, 66421, Homburg, Germany,
Subcell Biochem. 2012;56:301-22. doi: 10.1007/978-94-007-2199-9_16.
Cobalamin (Cbl, vitamin B12) consists of a corrinoid structure with cobalt in the centre of the molecule. Neither humans nor animals are able to synthesize this vitamin. Foods of animal source are the only natural source of cobalamin in human diet. There are only two enzymatic reactions in mammalian cells that require cobalamin as cofactor. Methylcobolamin is a cofactor for methionine synthase. The enzyme methylmalonyl-CoA-mutase requires adenosylcobalamin as a cofactor. Therefore, serum concentrations of homocysteine (tHcy) and methylmalonic acid (MMA) will increase in cobalamin deficiency. The cobalamin absorption from diet is a complex process that involves different proteins: haptocorrin, intrinsic factor and transcobalamin (TC). Cobalamin that is bound to TC is called holotranscobalamin (holoTC) which is the metabolically active vitamin B12 fraction. HoloTC consists 6 and 20% of total cobalamin whereas 80% of total serum cobalamin is bound to another binding protein, haptocorrin. Cobalamin deficiency is common worldwide. Cobalamin malabsorption is common in elderly subjects which might explain low vitamin status. Subjects who ingest low amount of cobalamin like vegetarians develop vitamin deficiency. No single parameter can be used to diagnose cobalamin deficiency. Total serum cobalamin is neither sensitive nor it is specific for cobalamin deficiency. This might explain why many deficient subjects would be overlooked by utilizing total cobalamin as status marker. Concentration of holotranscobalamin (holoTC) in serum is an earlier marker that becomes decreased before total serum cobalamin. Concentrations of MMA and tHcy increase in blood of cobalamin deficient subjects. Despite limitations of these markers in patients with renal dysfunction, concentrations of MMA and tHcy are useful functional markers of cobalamin status. The combined use of holoTC and MMA assays may better indicate cobalamin status than either of them. Because Cbl deficiency is a risk factor for neurodegenerative diseases an early diagnosis of a low B12 status is required which should be followed by an effective treatment in order to prevent irreversible damages.
钴胺素（Cbl，维生素B12）由一个类咕啉结构组成，其分子中心含有钴。人类和动物都无法合成这种维生素。动物源性食物是人类饮食中钴胺素的唯一天然来源。在哺乳动物细胞中，只有两种酶促反应需要钴胺素作为辅因子。甲钴胺素是甲硫氨酸合酶的辅因子。甲基丙二酰辅酶A变位酶需要腺苷钴胺素作为辅因子。因此，钴胺素缺乏时，血清同型半胱氨酸（tHcy）和甲基丙二酸（MMA）的浓度会升高。饮食中钴胺素的吸收是一个复杂的过程，涉及不同的蛋白质：运钴胺素蛋白、内因子和转钴胺素（TC）。与TC结合的钴胺素称为全转钴胺素（holoTC），它是具有代谢活性的维生素B12部分。HoloTC占总钴胺素的6%和20%，而血清总钴胺素的80%与另一种结合蛋白——运钴胺素蛋白结合。钴胺素缺乏在全球范围内都很常见。钴胺素吸收不良在老年受试者中很常见，这可能解释了维生素水平较低的原因。摄入钴胺素量低的受试者，如素食者，会出现维生素缺乏。没有单一参数可用于诊断钴胺素缺乏。血清总钴胺素对钴胺素缺乏既不敏感也不特异。这可能解释了为什么利用总钴胺素作为状态标志物会忽略许多缺乏的受试者。血清中全转钴胺素（holoTC）的浓度是一个较早的标志物，在血清总钴胺素降低之前就会下降。钴胺素缺乏受试者血液中MMA和tHcy的浓度会升高。尽管这些标志物在肾功能不全患者中有局限性，但MMA和tHcy的浓度是钴胺素状态有用的功能标志物。联合使用holoTC和MMA检测可能比单独使用它们更好地指示钴胺素状态。由于钴胺素缺乏是神经退行性疾病的一个危险因素，需要早期诊断低B12状态，随后应进行有效治疗以防止不可逆转的损害。
