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

The C-13-isotopomer enrichment of hepatic cytosolic acetyl-CoA of overnight-fed mice whose drinking water was supplemented with [U-C-13]fructose, and [1-C-13]glucose and p-amino benzoic acid (PABA) was quantified by C-13 NMR analysis of urinary N-acetyl-PABA. Four mice were given normal chow plus drinking water supplemented with 5% [1-C-13]glucose, 2.5% [U-C-13]fructose, and 2.5% fructose (Solution 1) overnight. Four were given chow and water containing 17.5% [1-C-13]glucose, 8.75% [U-C-13]fructose and 8.75% fructose (Solution 2). PABA (0.25%) was present in both studies. Urinary N-acetyl-PABA was analyzed by C-13 NMR. In addition to [2-C-13]- and [1,2-C-13]acetyl isotopomers from catabolism of [U-C-13]fructose and [1-C-13]glucose to acetyl-CoA, [1-C-13]acetyl was also found indicating pyruvate recycling activity. This precluded precise estimates of [1-C-13]glucose contribution to acetyl-CoA while that of [U-C-13]fructose was unaffected. The fructose contribution to acetyl-CoA from Solutions 1 and 2 was 4.0 +/- 0.4% and 10.6 +/- 0.6%, respectively, indicating that it contributed to a minor fraction of lipogenic acetyl-CoA under these conditions.