Quantification of hepatic transaldolase exchange activity and its effects on tracer measurements of indirect pathway flux in humans
✍ Scribed by John G. Jones; Paula Garcia; Cristina Barosa; Teresa C. Delgado; M. Madalena Caldeira; Luisa Diogo
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 118 KB
- Volume
- 59
- Category
- Article
- ISSN
- 0740-3194
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✦ Synopsis
Abstract
Exchange of hepatic glucose‐6‐phosphate (G6P) and glyceraldehyde‐3‐phosphate via transaldolase modifies hepatic G6P enrichment from glucose or gluconeogenic tracers. Transaldolase exchange was quantified in five healthy, fed subjects following an oral bolus of [1,2,3‐^13^C~3~]glycerol (25–30 mg/kg) and paracetamol (10–12 mg/kg). ^13^C Isotopomers of hepatic G6P were quantified by ^13^C NMR spectroscopy of urinary glucuronide. [1,2,3‐^13^C~3~]‐ and [4,5,6‐^13^C~3~]glucuronide isotopomers, representing the conversion of [1,2,3‐^13^C~3~]glycerol to G6P via dihydroxyacetone phosphate, were resolved from [1,2‐^13^C~2~]‐ and [5,6‐^13^C~2~]glucuronide ^13^C‐isotopomers, derived from metabolism of [1,2,3‐^13^C~3~]glycerol via pyruvate and phosphoenolpyruvate. Enrichment of [1,2,3‐^13^C~3~]glucuronide was significantly less than that of [4,5,6‐^13^C~3~]glucuronide (1.30 ± 0.57% versus 1.67 ± 0.42%, P < 0.05). Also, [1,2‐^13^C~2~]glucuronide enrichment was significantly less than that of [5,6‐^13^C~2~]glucuronide (0.28 ± 0.08% versus 0.36 ± 0.03%, P < 0.05). Transaldolase and triose phosphate isomerase exchange activities were estimated by applying the ^13^C‐isotopomer data to a model of hepatic sugar phosphate metabolism. Triose phosphate isomerase exchange was ≈99% complete and did not contribute significantly to the unequal ^13^C‐isotopomer distributions of the glucuronide triose halves. Instead, this was attributable to 25 ± 23% of hepatic G6P flux undergoing transaldolase exchange. This results in substantial overestimates of indirect pathway contributions to hepatic glycogen synthesis with tracers such as [5‐^3^H]glucose and ^2^H~2~O. Magn Reson Med, 2008. © 2008 Wiley‐Liss, Inc.