Noninvasive Measurement of Murine Hepatic Acetyl-CoA ¹³C-Enrichment Following Overnight Feeding with ¹³C-Enriched Fructose and Glucose

Figure 2

Schematic of acetyl-CoA isotopomer formation from [1-¹³C]glucose (blue filled circles) and [U-¹³C]fructose (red filled circles). For simplicity, unlabeled isotopomers are not shown. Conversion of the substrates to pyruvate generates a pair of pyruvate isotopomers (Pyruvate 1), and oxidation by pyruvate dehydrogenase yields a pair of acetyl-CoA isotopomers (Ac-CoA 1). Conversion of the substrates to pyruvate followed by complete cycling of pyruvate via Krebs cycle intermediates (oxaloacetate-malate-fumarate), represented by the dashed arrow, yields another set of pyruvate and acetyl-CoA isotopomers designated Pyruvate 2 and Ac-CoA 2. Isotopomers of Krebs cycle intermediates formed by incorporation of [1,2-¹³C₂]acetyl CoA and [2-¹³C]acetyl-CoA into the cycle also generate pyruvate and acetyl-CoA isotopmers via pyruvate cycling (pyruvate 3 and Ac-CoA 3). Unlike the previous cases, the two acetyl-CoA isotopomers (shown in green) cannot be traced to their parent ¹³C-substrates. The arrangement of pyruvate and acetyl-CoA into three groups is intended purely for illustrating isotopomer formation and does not imply compartmentation of these pools in situ.