Noninvasive approaches to tracing pathways in carbohydrate metabolism

Compounds that can be given safely in large quantity, conjugate with intermediates of carbohydrate metabolism in liver, and are excreted, allow large amounts of those intermediates to be isolated noninvasively. By administering labeled compounds that form those intermediates and determining the amount and/or distribution of label in those intermediates, the metabolism of those compounds can be traced. Thus, glucuronide formation has been used to sample hepatic uridine diphosphate glucose (UDP-glucose) and study glycogen metabolism and the pentose pathway, phenylacetate to sample hepatic alpha-ketoglutarate and estimate relative flux through the Krebs cycle, and acetylation to sample hepatic acetyl CoA. Interpretations require knowledge of the anatomical sites of formation of the intermediates, since more than one pool of an intermediate can exist in liver. The extent the labeled compound is metabolized in extrahepatic tissues also must be taken into account.