Origins of the hydrogen bound to carbon 1 of glucose in fasting: significance in gluconeogenesis quantitation.

Healthy subjects ingested2H2O.2H enriched the hydrogen bound to carbon 1 of blood glucose 1.3 to 1.8 times more than the hydrogens bound to carbon 6. Enrichment at carbon 1 was more than at carbon 5 after 14 h, but not after 42 h, of fasting. After overnight fasting, when [2,3-3H]succinate was infused, 34 times as much 3H was bound to carbon 6 as to carbon 1. On [1-2H,1-3H,1-14C]galactose infusion, the ratios of 2H to14C and of3H to14C in blood glucose were 30% less than in the galactose. 3H at carbon 6 was 1% of that at carbon 1 of the glucose. Thus, although the two hydrogens bound to carbon 1 and the two bound to carbon 6 of fructose 6-phosphate ( p) during gluconeogenesis are equally enriched in2H via pyruvate's equilibration with alanine, one of each is further enriched via hydration of fumarate that is converted to glucose. That hydrogen at carbon 1 of fructose 6-phosphate ( P) is also enriched in fructose 6- P's equilibration with mannose 6- P.2H from2H2O at carbon 1 to carbon 2 of blood glucose cannot then quantitate gluconeogenesis because of [1-2H]glucose formation during glycogenolysis. Triose-P cycling has a minimal effect on quantitation. 2H recovery in glucose from [1-2H]galactose does not quantitate galactose conversion via UDP-glucose to glycogen.