A limitation in the use of mass isotopomer distributions to measure
gluconeogenesis in fasting humans: hepatic heterogeneity in glycerol
metabolism.
Landau, Bernard R., Charles A. Fernandez, Stephen F. Previs, Karin Ekberg,
Visvanathan Chandramouli, John Wahren,satish C. Kalhan, and Henri
Brunengraber.
Departments of Medicine, Biochemistry, Biomedical Engineering, Pediatrics
and Nutrition, Case Western Reserve University School of Medicine, Cleveland,
Ohio 44l06 and the Department of Clinical Physiology, Karolinska Hospital S
-l7l 76, Stockholm Sweden
APStracts 2:0004E, 1995.
The use of distributions of mass isotopomers in glucose from [U
-13C]glycerol to estimate fractional rates of gluconeogenesis was examined.
[U-13C]Glycerol was infused into normal subjects who ingested
acetaminophen and fasted 60 h. Isotopomer distributions were measured by mass
spectrometry in blood glucose and in glucuronic acid from urinary
acetaminophen glucuronide. The distributions are incompatible with glucose
production solely via gluconeogenesis from a single pool of triose-P. Rather,
assuming a single enriched triose-P pool, the distributions indicate, despite
the 60-h fasting, about as much glucose formation from an unlabeled glucose
source as from that pool. Therefore, the data are concluded to indicate
cellular heterogeneity in glycerol's metabolism, so that two or more pools
with significantly different enrichments were the source of the glucose and
glucuronic acid. That heterogeneity is related to much greater concentrations
of glycerol in periportal than pericentral zones of the liver lobule. Beyond
evidence for heterogeneity, the findings emphasize a limitation in applying
analyses of mass isotopomer distributions to measure polymer biosynthesis in
the presence of heterogeneity in the precursor pool.
Received 14 November 1994; accepted in final form 9 January 1995.
APS Manuscript Number E470-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 February 1995.