EVALUATION OF HOLO-TRANSCOBALAMIN AS AN INDICATOR OF VITAMIN B12 ABSORPTION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。维生素B12（B12）是一种必需的膳食营养素，作为两种主要代谢反应所需的辅酶。缺乏B12可能是由于饮食不足，但更常见的是由于B12吸收不良，这可能导致贫血，不可逆的神经损伤和出生缺陷影响怀孕。需要改进的临床诊断测试来检测B12吸收不良，以便可以实施有效的B12治疗。本研究旨在提供与口服B12剂量后B12转运蛋白转钴胺素（TC）变化相关的初步数据，这些数据可用于设计B12吸收不良的新诊断试验。B12在被粘膜上皮细胞摄取后迅速与TC结合（holo-TC），半衰期短，对B12摄入量和短期状态的变化比血清B12浓度更敏感。假设holo-TC浓度可用作B12吸收的指标。本研究的主要目的是评价口服B12后holo-TC浓度的变化。具有高正常（血清B12 =444 pmol/L）维生素B12状态的健康个体将在三次单独口服剂量（9？g/剂），随后在第2天和第3天抽取一份空腹血样。将测量Holo-TC和其他B12反应指数，以评估Holo-TC对补充B12的反应变化。这项初步研究的数据将有助于设计未来的研究，其长期目标是开发新的和改进的B12诊断吸收试验。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Vitamin B12 (B12) is an essential dietary nutrient required as a coenzyme for two major metabolic reactions. A deficiency of B12 may result from dietary inadequacies but more commonly results from B12 malabsorption, which may lead to anemia, irreversible neurological damage, and birth defect-affected pregnancies. Improved clinical diagnostic tests are needed to detect B12 malabsorption so that effective B12 therapy can be implemented. This study is designed to provide pilot data related to changes in a B12 transport protein, transcobalamin (TC) in response to oral B12 doses that may be used to design a new diagnostic test for B12 malabsorption. B12 binds to TC (holo-TC) rapidly after uptake by the mucosal epithelial cell, has a short half-life, and is more sensitive to changes in B12 intake and short-term status than serum B12 concentration. It is hypothesized that holo-TC concentration may be used as an indicator of B12 absorption. The primary objective of this study is to evaluate changes in holo-TC concentration in response to oral doses of B12. Healthy individuals with high-normal (serum B12 =444 pmol/L) vitamin B12 status will have blood drawn at timed intervals prior to and following three separate oral doses (9 ?g/dose) on Day 1 followed by one fasting blood sample drawn on Days 2 and 3. Holo-TC and other B12 response indices will be measured to evaluate changes in holo-TC in response to supplemental B12. The data from this pilot study will be useful in designing future studies with the long-term goal of developing new and improved diagnostic absorption tests for B12.