Metabolomic and mass isotopomer analysis of liver gluconeogenesis and citric acid cycle: II. Heterogeneity of metabolite labeling pattern.
In this second of two companion articles, we compare the mass isotopomer distribution of metabolites of liver gluconeogenesis and citric acid cycle labeled from NaH(13)CO(3) or dimethyl [1,4-(13)C(2)]succinate. The mass isotopomer distribution of intermediates reveals the reversibility of the isocitrate dehydrogenase + aconitase reactions, even in the absence of a source of alpha-ketoglutarate. In addition, in many cases, a number of labeling incompatibilities were found as follows: (i) glucose versus triose phosphates and phosphoenolpyruvate; (ii) differences in the labeling ratios C-4/C-3 of glucose versus (glyceraldehyde 3-phosphate)/(dihydroxyacetone phosphate); and (iii) labeling of citric acid cycle intermediates in tissue versus effluent perfusate. Overall, our data show that gluconeogenic and citric acid cycle intermediates cannot be considered as sets of homogeneously labeled pools. This probably results from the zonation of hepatic metabolism and, in some cases, from differences in the labeling pattern of mitochondrial versus extramitochondrial metabolites. Our data have implications for the use of labeling patterns for the calculation of metabolic rates or fractional syntheses in liver, as well as for modeling liver intermediary metabolism.
Yang
Lili
L
Departments of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Kasumov
Takhar
T
Kombu
Rajan S
RS
Zhu
Shu-Han
SH
Cendrowski
Andrea V
AV
David
France
F
Anderson
Vernon E
VE
Kelleher
Joanne K
JK
Brunengraber
Henri
H
D000818:Animals; D002247:Carbon Isotopes / Q000378:metabolism; D019343:Citric Acid / Q000378:metabolism; D002952:Citric Acid Cycle / Q000502:physiology*; D005943:Gluconeogenesis / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D007553:Isotope Labeling; D007651:Keto Acids / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D010728:Phosphoenolpyruvate / Q000378:metabolism; D051381:Rats; D013403:Sugar Phosphates / Q000378:metabolism
D002247:Carbon Isotopes; D007651:Keto Acids; D007656:Ketoglutaric Acids; D013403:Sugar Phosphates; D019343:Citric Acid; D010728:Phosphoenolpyruvate; D007521:Isocitrate Dehydrogenase; D005947:Glucose