Liu Yi-qun, Liu Ying, Morita Tatsuya, Mori Makoto, Sugiyama Kimio
The United Graduate School of Agricultural Science, Gifu University, 1-1, Yanagido, Gifu 501-1193, Japan.
J Nutr Sci Vitaminol (Tokyo). 2012;58(2):78-87. doi: 10.3177/jnsv.58.78.
The mechanism by which feeding a higher casein diet results in resistance to choline deprivation-induced hyperhomocysteinemia was investigated in rats. Plasma homocysteine concentration was significantly lower in rats fed a 30% casein diet (30C) than in rats fed a 10% casein diet (10C). Choline deprivation did not enhance plasma homocysteine concentration in rats fed 30C, while it significantly enhanced plasma homocysteine concentration in rats fed 10C. The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 10C was significantly suppressed by methionine supplementation in a dose-dependent manner in the range of 0.1 to 0.3%, but the suppressive effect of methionine became smaller with an increase in supplementation level in the range of 0.3 to 0.5%. At a 0.5% supplementation level, methionine did not exhibit any suppressive effect on choline deprivation-induced hyperhomocysteinemia. The higher plasma homocysteine concentration in rats fed choline-deprived 10C+0.5% methionine was significantly decreased by concurrent supplementation with 0.32% glycine+0.94% serine to the level of rats fed 10C. Raising dietary total amino acid level by adding 3.61% branched-chain amino acids (BCAA)+4.5% acidic amino acids (AAA) to choline-deprived 10C+0.5% methionine+0.32% glycine+0.94% serine resulted in a further decrease in plasma homocysteine concentration to a level lower than the level in rats fed 10C. Choline deprivation-induced increases in hepatic S-adenosylhomocysteine and homocysteine concentrations were significantly suppressed by supplementation with glycine+serine and further suppressed by BCAA+AAA. Hepatic cystathionine β-synthase activity and its gene expression were significantly increased by BCAA+AAA. Hepatic triglyceride concentration changed in a manner similar to that of plasma homocysteine concentration. The results indicate that there are at least three factors contributing to the resistivity of rats fed a higher casein diet (30C) to choline deprivation-induced hyperhomocysteinemia, i.e., higher intake of methionine, higher intake of glycine and serine, and higher intake of other amino acids such as BCAA and AAA.
在大鼠中研究了喂食较高酪蛋白饮食导致对胆碱缺乏诱导的高同型半胱氨酸血症产生抗性的机制。喂食30%酪蛋白饮食（30C）的大鼠血浆同型半胱氨酸浓度显著低于喂食10%酪蛋白饮食（10C）的大鼠。胆碱缺乏并未提高喂食30C大鼠的血浆同型半胱氨酸浓度，而在喂食10C的大鼠中显著提高了血浆同型半胱氨酸浓度。在0.1%至0.3%范围内，蛋氨酸补充剂以剂量依赖的方式显著抑制了喂食10C大鼠中胆碱缺乏诱导的血浆同型半胱氨酸浓度升高，但在0.3%至0.5%范围内，随着补充水平的增加，蛋氨酸的抑制作用变小。在0.5%的补充水平下，蛋氨酸对胆碱缺乏诱导的高同型半胱氨酸血症未表现出任何抑制作用。同时补充0.32%甘氨酸+0.94%丝氨酸可使喂食胆碱缺乏的10C+0.5%蛋氨酸大鼠中较高的血浆同型半胱氨酸浓度显著降低至喂食10C大鼠的水平。通过向胆碱缺乏的10C+0.5%蛋氨酸+0.32%甘氨酸+0.94%丝氨酸中添加3.61%支链氨基酸（BCAA）+4.5%酸性氨基酸（AAA）来提高饮食总氨基酸水平，导致血浆同型半胱氨酸浓度进一步降低至低于喂食10C大鼠的水平。补充甘氨酸+丝氨酸可显著抑制胆碱缺乏诱导的肝脏S-腺苷同型半胱氨酸和同型半胱氨酸浓度升高，而BCAA+AAA可进一步抑制。BCAA+AAA显著提高了肝脏胱硫醚β-合酶活性及其基因表达。肝脏甘油三酯浓度的变化方式与血浆同型半胱氨酸浓度相似。结果表明，至少有三个因素导致喂食较高酪蛋白饮食（30C）的大鼠对胆碱缺乏诱导的高同型半胱氨酸血症具有抗性，即蛋氨酸摄入量较高、甘氨酸和丝氨酸摄入量较高以及其他氨基酸（如BCAA和AAA）摄入量较高。
