Yang D, Previs S F, Fernandez C A, Dugelay S, Soloviev M V, Hazey J W, Agarwal K C, Levine W C, David F, Rinaldo P, Beylot M, Brunengraber H
Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Am J Physiol. 1996 May;270(5 Pt 1):E882-9. doi: 10.1152/ajpendo.1996.270.5.E882.
In human and primate liver, phenylacetate and glutamine form phenylacetylglutamine, which is excreted in urine. Probing noninvasively the labeling pattern of liver citric acid cycle intermediates with phenylacetylglutamine assumes that the labeling pattern of its glutamine moiety reflects that of liver alpha-ketoglutarate. To validate this probe, we infused monkeys with [U-13C3]lactate, [3-13C]lactate, [1, 2-13C2]acetate, [2-13C]acetate, [U-13C3]glycerol, or 2-[3-13C]ketoisocaproate and compared the labeling patterns of urinary phenylacetyl-glutamine with those of glutamate and glutamine in liver, plasma, muscle, and kidney and liver alpha-ketoglutarate. Only with [U-13C3]lactate or [3-13C]lactate does the labeling pattern of phenylacetylglutamine reflect patterns of liver alpha-ketoglutarate and glutamate. With [13C]acetate, muscle and kidney glutamate are more labeled than liver metabolites. This confirms that with [13C]acetate, the labeling pattern of liver metabolites is influenced by 13CO2 and [13C]glutamine made in peripheral tissues. Our data validate the use of phenylacetylglutamine labeled from [3-13C]lactate or [3-13C]pyruvate to probe noninvasively the pyruvate carboxylase-to-pyruvate dehydrogenase flux ratio in human subjects.
在人类和灵长类动物的肝脏中，苯乙酸和谷氨酰胺形成苯乙酰谷氨酰胺，并通过尿液排出。用苯乙酰谷氨酰胺对肝脏柠檬酸循环中间体的标记模式进行无创探测，假定其谷氨酰胺部分的标记模式反映了肝脏α-酮戊二酸的标记模式。为了验证这种探针，我们给猴子输注了[U-13C3]乳酸、[3-13C]乳酸、[1,2-13C2]乙酸、[2-13C]乙酸、[U-13C3]甘油或2-[3-13C]酮异己酸，并比较了尿中苯乙酰谷氨酰胺与肝脏、血浆、肌肉和肾脏中谷氨酸和谷氨酰胺以及肝脏α-酮戊二酸的标记模式。只有使用[U-13C3]乳酸或[3-13C]乳酸时，苯乙酰谷氨酰胺的标记模式才反映肝脏α-酮戊二酸和谷氨酸的模式。使用[13C]乙酸时，肌肉和肾脏中的谷氨酸比肝脏代谢物标记更多。这证实了使用[13C]乙酸时，肝脏代谢物的标记模式受外周组织中产生的13CO2和[13C]谷氨酰胺的影响。我们的数据验证了使用由[3-13C]乳酸或[3-13C]丙酮酸标记的苯乙酰谷氨酰胺对人类受试者丙酮酸羧化酶与丙酮酸脱氢酶通量比率进行无创探测的方法。
