NONINVASIVE PROBING OF CITRIC-ACID CYCLE INTERMEDIATES IN PRIMATE LIVER WITH PHENYLACETYLGLUTAMINE

In human and primate liver, phenylacetate and glutamine form phenylace tylglutamine, which is excreted in urine. Probing noninvasively the la beling pattern of liver citric acid cycle intermediates with phenylace tylglutamine assumes that the labeling pattern of its glutamine moiety reflects that of liver alpha-ketoglutarate. To validate this probe, w e infused monkeys with [U-C-13(3)]lactate, [3-C-13]lactate, [1, 2-C-13 (2)]acetate, [2-C-13] acetate, [U-C-13(3)]glycerol, or 2-[3-C-13] keto isocaproate and compared the labeling patterns of urinary phenylacetyl glutamine with those of glutamate and glutamine in liver, plasma, musc le, and kidney and liver alpha-ketoglutarate. Only with [U-C-13(3)]lac tate or [3-C-13]lactate does the labeling pattern of phenylacetylgluta mine reflect patterns of liver alpha-ketoglutarate and glutamate. With [C-13]acetate, muscle and kidney glutamate are more labeled than live r metabolites. This confirms that with [C-13]acetate, the labeling pat tern of liver metabolites is influenced by (CO2)-C-13 and [C-13]glutam ine made in peripheral tissues. Our data validate the use of phenylace tylglutamine labeled from [3-C-13]lactate or [3-C-13]pyruvate to probe noninvasively the pyruvate carboxyl ase-to-pyruvate dehydrogenase flu x ratio in human subjects.