McCormick Donald B
Department of Biochemistry and Program in Nutrition and Health Sciences, Emory University, Atlanta, GA 30322-3050, USA.
Nutr Res Rev. 2002 Dec;15(2):245-62. doi: 10.1079/NRR200241.
Following identification of essential micronutrients, there has been a continuum of research aimed at revealing their absorption, transport, utilization as cofactors, and excretion and secretion. Among those cases that have received our attention are vitamin B6, riboflavin, biotin, lipoate, ascorbate, and certain metal ions. Circulatory transport and cellular uptake of the water-soluble vitamins exhibit relative specificity and facilitated mechanisms at physiological concentrations. Isolation of enzymes and metabolites from micro-organisms and mammals has provided information on pathways involved in cofactor formation and metabolism. Kinases catalysing phosphorylation of B6 and riboflavin have a preference for Zn2+ in stereospecific chelates with adenosine triphosphate. The synthetase for flavin adenine dinucleotide prefers Mg2+. The flavin mononucleotide-dependent oxidase that converts the 5'-phosphates of pyridoxine and of pyridoxamine to pyridoxal phosphate is a connection between B6 and riboflavin and is a primary control point for conversion of B6 to its coenzyme. Sequencing and cloning of a side-chain oxidase for riboflavin was achieved. Details on binding and function have been delineated for some cofactor systems, especially in several flavoproteins. There is both photochemical oxidation and oxidative catabolism of B6 and riboflavin. Both biotin and lipoate undergo oxidation of their acid side chains with redox cleavage of the rings. Applications from our findings include the development of affinity absorbents, enhanced drug delivery, delineation of residues in biopolymer modification, pathogen photoinactivation in blood components, and input into human dietary recommendations. Ongoing and future research in the cofactor arena can be expected to add to this panoply. At the molecular level, the way in which the same cofactor can participate in diverse catalytic reactions resides in interactions with surrounding enzyme structures that must be determined case by case. At the level of human intake, more knowledge is desirable for making micronutrient recommendations based on biochemical indicators, especially for the span between infancy and adulthood.
在确定必需的微量营养素之后，一系列研究持续开展，旨在揭示它们的吸收、转运、作为辅助因子的利用以及排泄和分泌情况。我们关注的此类物质包括维生素B6、核黄素、生物素、硫辛酸、抗坏血酸以及某些金属离子。水溶性维生素的循环运输和细胞摄取在生理浓度下表现出相对特异性和促进机制。从微生物和哺乳动物中分离酶和代谢物，为了解辅助因子形成和代谢所涉及的途径提供了信息。催化B6和核黄素磷酸化的激酶在与三磷酸腺苷形成立体特异性螯合物时对Zn2+有偏好。黄素腺嘌呤二核苷酸合成酶偏好Mg2+。将吡哆醇和吡哆胺的5'-磷酸转化为磷酸吡哆醛的黄素单核苷酸依赖性氧化酶是B6和核黄素之间的联系，也是B6转化为辅酶的主要控制点。实现了核黄素侧链氧化酶的测序和克隆。对于一些辅助因子系统，特别是几种黄素蛋白，已经阐明了其结合和功能的细节。B6和核黄素都存在光化学氧化和氧化分解代谢。生物素和硫辛酸的酸性侧链都会发生氧化，并伴随环的氧化还原裂解。我们研究结果的应用包括开发亲和吸附剂、增强药物递送、确定生物聚合物修饰中的残基、血液成分中病原体的光灭活以及为人类饮食建议提供参考。预计在辅助因子领域正在进行的和未来的研究将进一步丰富这一内容。在分子水平上，同一辅助因子能够参与多种催化反应的方式，取决于与周围酶结构的相互作用，这必须逐例确定。在人类摄入水平上，基于生化指标制定微量营养素建议需要更多知识，特别是在婴儿期到成年期这一阶段。
