B12 Nutrition in the Aged

描述（由申请人提供）：高同型半胱氨酸血症（高血清总同型半胱氨酸）仍然是老年人的一个问题，即使在这个时代的高度叶酸强化食品在美国。这种矛盾的解释是因为许多老年人继续有未确诊和未经治疗的维生素B 12缺乏症，如血清甲基丙二酸浓度升高所示。由于维生素缺乏或肾功能衰竭引起的高同型半胱氨酸血症可能导致S-腺苷高半胱氨酸升高，S-腺苷甲硫氨酸/S-腺苷高半胱氨酸比值较低，这可能损害脑神经递质、磷脂和髓鞘的关键甲基化。本研究采用稳定同位素稀释液相色谱/质谱联用技术研究了老年人和维生素缺乏性肾功能衰竭大鼠血浆同型半胱氨酸与S-腺苷蛋氨酸、S-腺苷同型半胱氨酸及其比值的关系。将在患有维生素B 12缺乏和/或血清S-腺苷高半胱氨酸浓度升高的老年人中研究高剂量口服维生素B 12和叶酸治疗后血清和尿液代谢物的模式。基线和治疗后S-腺苷甲硫氨酸和S-腺苷同型半胱氨酸及其比值与抑郁和神经系统症状相关。将在来自B 12缺陷大鼠的组织和细胞培养模型中研究甲硫氨酸代谢的酶，例如胱硫醚β-合酶、γ-胱硫醚酶、甲硫氨酸腺苷转移酶和S-腺苷高半胱氨酸水解酶。这些研究的长期目标是确定维生素B 12缺乏是否会损害S-腺苷甲硫氨酸和S-腺苷高半胱氨酸的平衡。由于治疗和并发症可能不同，因此将确定肾功能不全的尿液和血清代谢物模式是否可与维生素B 12缺乏症区分。在维生素B 12缺乏和肾功能不全的情况下，将获得对甲硫氨酸代谢调节的控制的新理解，这些情况在临床上仍然是重要的，并且对于这些情况，用维生素或S-腺苷甲硫氨酸补充剂治疗将是安全的和广泛可用的。

DESCRIPTION (provided by applicant): Hyperhomocysteinemia (high serum total homocysteine) remains a problem for seniors even in this era of highly folate-fortified food in the United States. This paradox is explained because many seniors continue to have undiagnosed and untreated vitamin B 12 deficiency as shown by elevated serum methylmalonic acid concentrations. Hyperhomocysteinemia due to vitamin deficiency or renal failure may cause elevations of S-adenosylhomocysteine with a low S-adenosylmethionine/S-adenosylhomocysteine ratio, which may impair crucial methylations of brain neurotransmitters, phospholipids and myelin. A new stable isotope dilution liquid chromatography/mass spectrometry method will be used to explore the relationships between homocysteine and S-adenosylmethionine, S-adenosylhomocysteine and ratio in human seniors and rats with vitamin deficiency and renal failure. The pattern of the serum and urine metabolites will be studied after high dose oral vitamin B 12 and folic acid treatment in seniors who have vitamin B 12 deficiency and/or elevated serum S-adenosylhomocysteine concentrations. The baseline and post treatment S-adenosylmethionine and S-adenosylhomocysteine and ratio will be correlated with depression and neurologic symptoms. Enzymes of methionine metabolism such as cystathionine beta-synthase, gamma-cystathionase, methionine adenosyltransferase and S-adenosylhomocysteine hydrolase will be studied in tissues from B 12 deficient rats and in cell culture models. The long term goals of these studies are to determine whether vitamin B 12 deficiency impairs the balance of S-adenosylmethionine and S-adenosylhomocysteine. It will be determined whether the pattern of urine and serum metabolites in renal insufficiency could be differentiated from vitamin B 12 deficiency since treatment and complications might be different. New understanding of the control of regulation of methionine metabolism will be obtained in the setting of vitamin B 12 deficiency and renal insufficiency, conditions which continue to be important clinically and for which treatment with vitamins or S-adenosylmethionine supplements will be safe and widely available.