Burgert S L, Andersen D W, Stegink L D, Takeuchi H, Schedl H P
Department of Medicine, University of Iowa, Iowa City.
Metabolism. 1991 Jun;40(6):612-8. doi: 10.1016/0026-0495(91)90052-x.
The intestinal metabolism of aspartame (N-L-alpha-aspartyl-L-phenylalanine methyl ester; APM) and its L-phenylalanine methyl ester (PME) decomposition product was evaluated in six young pigs. Equimolar doses (2.5 mmol/kg body weight) of APM, PME, and L-phenylalanine (PHE) administered to the proximal jejunum produced similar increases in portal blood PHE concentrations. Methanol, nondetectable in portal blood after PHE ingestion, increased markedly after administration of either APM or PME. Portal blood aspartate concentrations were unchanged after PME and PHE administration, but increased significantly after APM administration. Increases in portal blood PHE concentrations were significantly greater than were increases in aspartate concentrations following APM administration. Neither APM, PME, nor aspartyl-phenylalanine (AspPhe) were detected in portal or vena caval blood following administration of any test compound. Steady-state perfusion of the small intestine with APM showed a net intraluminal appearance rate of AspPhe at 36% of the disappearance rate of APM. During steady-state PME perfusion, PHE had a significantly greater net appearance rate than during APM perfusion. Methanol appearance rates were slightly, but not significantly, higher during PME than during APM perfusions. The data suggest that (1) APM is hydrolyzed to AspPhe and both APM and PME are hydrolyzed to their constituent amino acids and and methanol prior to entering the portal circulation; (2) AspPhe is an important intraluminal intermediate in aspartame metabolism; and (3) aspartate is rapidly metabolized by the enterocyte.
在六头幼猪中评估了阿斯巴甜（N-L-α-天冬氨酰-L-苯丙氨酸甲酯；APM）及其L-苯丙氨酸甲酯（PME）分解产物的肠道代谢情况。向空肠近端给予等摩尔剂量（2.5 mmol/kg体重）的APM、PME和L-苯丙氨酸（PHE），可使门静脉血中PHE浓度出现相似程度的升高。PHE摄入后门静脉血中未检测到甲醇，但给予APM或PME后甲醇显著增加。给予PME和PHE后门静脉血中天冬氨酸浓度未变，但给予APM后显著升高。给予APM后门静脉血中PHE浓度的升高显著大于天冬氨酸浓度的升高。给予任何一种受试化合物后，门静脉血或腔静脉血中均未检测到APM、PME或天冬氨酰苯丙氨酸（AspPhe）。用APM对小肠进行稳态灌注显示，AspPhe的腔内净出现率为APM消失率的36%。在PME稳态灌注期间，PHE的净出现率显著高于APM灌注期间。PME灌注期间甲醇的出现率略高于APM灌注期间，但差异不显著。数据表明：（1）APM水解为AspPhe，并且APM和PME在进入门静脉循环之前均水解为其组成氨基酸和甲醇；（2）AspPhe是阿斯巴甜代谢过程中重要的腔内中间体；（3）天冬氨酸被肠细胞迅速代谢。
