Matsueda S, Niiyama Y
J Nutr Sci Vitaminol (Tokyo). 1982 Oct;28(5):557-73. doi: 10.3177/jnsv.28.557.
The effects of diets, each with an excess of one essential amino acid, on the maintenance of pregnancy and fetal growth were investigated in rats. Rats were fed on 6% casein diet containing 5% threonine, methionine, valine, isoleucine, leucine, tyrosine, phenylalanine, tryptophan, or lysine from day 1 to day 14 or 21 of pregnancy. Excess methionine and leucine diets resulted in complete and 80% loss of fetuses, respectively. This fetal wastage was prevented by daily injection of 0.5 microgram of estrone and 4 mg of progesterone. Judging from the total food consumptions and body weight gains during pregnancy, methionine had the most severe effects, followed in order by leucine, tryptophan, valine, lysine, isoleucine, threonine, phenylalanine, and tyrosine. The weights of fetuses in the excess amino acid groups were significantly lower than those in the respective pair-fed controls. Excess aromatic amino acids caused growth retardation of fetal brain, although the levels of free tyrosine and phenylalanine in fetal brain were not high. The concentrations of free methionine and threonine were markedly elevated in the maternal plasma when these amino acids were fed in excess, but those of other amino acids were not increased appreciably by excess amounts in the diet. Changes in the maternal plasma levels of individual amino acids other than those in excess in the diet were small. On the contrary, the levels of not only the excess amino acids but also of other amino acids in fetal brains were appreciably elevated by these diets. These findings suggest that the blood-brain barrier is immature and that the synthesis of proteins in fetal brain is impaired by excess amino acids in the mothers. The importance of experiments on diets with excess of single amino acids in pregnant animals is discussed in connection with studies on inborn errors of amino acid metabolism.
研究了每种都含有一种必需氨基酸过量的日粮对大鼠维持妊娠和胎儿生长的影响。从妊娠第1天至第14天或第21天,给大鼠喂食含5%苏氨酸、蛋氨酸、缬氨酸、异亮氨酸、亮氨酸、酪氨酸、苯丙氨酸、色氨酸或赖氨酸的6%酪蛋白日粮。过量蛋氨酸和亮氨酸日粮分别导致胎儿完全损失和80%损失。每天注射0.5微克雌酮和4毫克孕酮可防止这种胎儿损耗。从妊娠期间的总食物消耗量和体重增加来看,蛋氨酸的影响最严重,其次依次为亮氨酸、色氨酸、缬氨酸、赖氨酸、异亮氨酸、苏氨酸、苯丙氨酸和酪氨酸。过量氨基酸组胎儿的体重显著低于各自成对喂食对照组的胎儿体重。过量芳香族氨基酸导致胎儿脑生长迟缓,尽管胎儿脑中游离酪氨酸和苯丙氨酸的水平不高。当这些氨基酸过量喂食时,母体血浆中游离蛋氨酸和苏氨酸的浓度显著升高,但日粮中过量的其他氨基酸并未使它们的浓度明显增加。日粮中未过量的单个氨基酸的母体血浆水平变化很小。相反,这些日粮不仅使过量氨基酸,而且使胎儿脑中其他氨基酸的水平明显升高。这些发现表明血脑屏障不成熟,母亲体内过量氨基酸会损害胎儿脑内蛋白质的合成。结合氨基酸代谢先天性缺陷的研究,讨论了对怀孕动物进行单一氨基酸过量日粮实验的重要性。