Sources of hepatic glycogen synthesis during an oral glucose tolerance test: Effect of transaldolase exchange on flux estimates.
Sources of hepatic glycogen synthesis during an oral glucose tolerance test were evaluated in six healthy subjects by enrichment of a 75-g glucose load with 6.67% [U-(13)C]glucose and 3.33% [U-(2)H(7)]glucose and analysis of plasma glucose and hepatic uridine diphosphate-glucose enrichments (sampled as urinary menthol glucuronide) by (2)H and (13)C nuclear magnetic resonance. The direct pathway contribution, as estimated from the dilution of [U-(13)C]glucose between plasma glucose and glucuronide, was unexpectedly low (36 +/- 5%). With [U-(2)H(7)]glucose, direct pathway estimates based on the dilution of position 3 (2)H-enrichment between plasma glucose and glucuronide were significantly higher (51 +/- 6%, P = 0.05). These differences reflect the exchange of the carbon 4, 5, and 6 moiety of fructose-6-phosphate and glyceraldehyde-3-phosphate catalyzed by transaldolase. As further evidence of this exchange, (2)H-enrichments in glucuronide positions 4 and 5 were inferior to those of position 3. From the difference in glucuronide positions 5 and 3 enrichments, the fraction of direct pathway carbons that experienced transaldolase exchange was estimated at 21 +/- 4%. In conclusion, the direct pathway contributes only half of hepatic glycogen synthesis during an oral glucose tolerance test. Glucose tracers labeled in positions 4, 5, or 6 will give significant underestimates of direct pathway activity because of transaldolase exchange.
NMR Laboratory, Center for Neurosciences and Cell Biology, Coimbra University, Coimbra, Portugal.
Teresa C
TC
Delgado
Claúdia
C
Silva
Isabel
I
Fernandes
Madalena
M
Caldeira
Margarida
M
Bastos
Carla
C
Baptista
Manuela
M
Carvalheiro
Carlos F G C
CF
Geraldes
John G
JG
Jones
D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005951:Glucose Tolerance Test / Q000379:methods*; D006003:Glycogen / Q000096:biosynthesis*; D006801:Humans; D007328:Insulin / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D014153:Transaldolase / Q000097:blood*
D001786:Blood Glucose; D007328:Insulin; D006003:Glycogen; D014153:Transaldolase; D005947:Glucose