Synthesis of essential amino acids from their alpha-keto analogues by perfused rat liver and muscle.
Synthesis of essential amino acids from their alpha-keto analogues by perfused rat liver and muscle.
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通过灌注大鼠肝脏和肌肉从其α-酮类似物合成必需氨基酸。
DOI：
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发表时间：
1973
影响因子：
15.9
通讯作者：
A. Coulter
中科院分区：
文献类型：
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作者：
M. Walser;P. Lund;N. Ruderman;A. Coulter
大多数必需氨基酸可以在饮食中被其α-酮类似物替代。因此，这些酮酸被提议作为膳食蛋白质的替代品。为了确定它们在正常动物组织中的命运，用缬氨酸、亮氨酸、异亮氨酸、甲硫氨酸或苯丙氨酸的酮类似物灌注离体大鼠肝脏和后躯（肌肉）制剂。当以1.5-2.0 mM灌注时，所有五种化合物均被48 h饥饿大鼠的肝脏迅速利用，速率为每200 g大鼠49至155 mumol/h。相应的氨基酸以显著增加的浓度出现在培养基中。灌注苯丙酮酸也导致酪氨酸的外观。尿素释放无变化。在冷冻夹闭的肝脏代谢物浓度的测量显示两个异常，特别是在5 mM或以上的酮酸浓度：α-酮戊二酸大幅增加，和组织谷氨酰胺中度至显著减少。这种减少在数量上足以解释新合成的氨基酸中出现的氮。用浓度为1.3-8.0 mM的相同酮酸灌注喂食大鼠的隔离后躯。所有动物均以1.4 - 7.0 mumol/h/g肌肉灌注的速率使用。相应的氨基酸以大大增加的速率释放。丙氨酸和谷氨酸水平下降，在一些灌注，但在肌肉中的主要氮供体没有确定;谷氨酰胺在组织中的含量，其释放到灌注液的速率保持不变。
Most essential amino acids can be replaced by their alpha-keto-analogues in the diet. These ketoacids have therefore been proposed as substitutes for dietary protein. In order to determine their fate in tissues of normal animals, isolated rat liver and hindquarter (muscle) preparations were perfused with keto-analogues of valine, leucine, isoleucine, methionine, or phenylalanine. When perfused at 1.5-2.0 mM, all five compounds were utilized rapidly by the liver of 48-h starved rats, at rates varying from 49 to 155 mumol/h per 200g rat. The corresponding amino acids appeared in the medium in significantly increased concentrations. Perfusion with phenylpyruvate also led to the appearance of tyrosine. Urea release was unaltered. Measurement of metabolite concentrations in freeze-clamped liver revealed two abnormalities, particularly at ketoacid concentrations of 5 mM or above: a large increase in alpha-ketoglutarate, and a moderate to marked decrease in tissue glutamine. This decrease was quantitatively sufficient to account for nitrogen appearing in newly synthesized amino acids. Isolated hindquarters of fed rats were perfused with the same ketoacids at concentrations of 1.3-8.0 mM. All were utilized at rates varying from 1.4 to 7.0 mumol/h per g muscle perfused. The corresponding amino acids were released at greatly increased rates. Alanine and glutamate levels fell in some perfusions, but the principal nitrogen donor in muscle was not identified; the content of glutamine in tissue, and its rate of release into the perfusate remained constant.