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，即使在这个高度叶酸强化食品的时代在美国。这一悖论可以解释为，许多老年人仍未确诊和未经治疗的维生素b12缺乏症，如血清甲基丙二酸浓度升高所示。维生素缺乏或肾功能衰竭引起的高同型半胱氨酸血症可导致s -腺苷基蛋氨酸/ s -腺苷基同型半胱氨酸比例低的s -腺苷基半胱氨酸升高，这可能损害脑神经递质、磷脂和髓磷脂的关键甲基化。采用稳定同位素稀释液相色谱/质谱联用方法，探讨老年人和维生素缺乏症、肾功能衰竭大鼠体内同型半胱氨酸与s -腺苷甲硫氨酸、s -腺苷同型半胱氨酸及其比值的关系。对维生素b12缺乏和/或血清s -腺苷型同型半胱氨酸浓度升高的老年人进行大剂量口服维生素b12和叶酸治疗后，将研究其血清和尿液代谢物的模式。基线和治疗后s -腺苷蛋氨酸和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b12缺乏大鼠组织和细胞培养模型中研究蛋氨酸代谢酶，如半胱甘氨酸β -合成酶、γ -半胱甘氨酸酶、蛋氨酸腺苷转移酶和s -腺苷同型半胱氨酸水解酶。这些研究的长期目标是确定维生素b12缺乏是否会损害s -腺苷蛋氨酸和s -腺苷同型半胱氨酸的平衡。肾功能不全的尿液和血清代谢物的模式是否可以与维生素b12缺乏症区分开来，因为治疗和并发症可能不同。在维生素b12缺乏和肾功能不全的情况下，将获得对蛋氨酸代谢调控控制的新认识，这些情况在临床上仍然很重要，并且用维生素或s -腺苷蛋氨酸补充剂治疗将是安全且广泛可用的。

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.