D-glucose generation from [2-13C]pyruvate in rat hepatocytes: implications in terms of enzyme-to-enzyme channelling.
In rat hepatocytes exposed to [2-13C]pyruvate, newly formed glucose was more efficiently labeled in the carbon C5 than C2, as well as in the carbon C6 than C1, suggesting enzyme-to-enzyme channeling of D-glyceraldehyde 3-phosphate between glyceraldehyde-3-phosphate dehydrogenase and phosphofructoaldolase. Likewise the C1/C2 and C6/C5 ratios for 13C abundance in newly formed glucose, which largely exceeded the C3/C2 ratio of lactate or alanine and could reflect reversibility in the fumarase reaction, were compatible with the enzyme-to-enzyme tunneling of symmetrical Krebs cycle intermediates in the sequence of reactions catalyzed by succinyl-CoA synthetase, succinate dehydrogenase, and fumarase. This study further indicates that the major fraction of pyruvate is metabolized via pyruvate carboxylase rather than pyruvate dehydrogenase.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University (ULB), Belgium.
Zhang
T M
TM
Verbruggen
I
I
Willem
R
R
D000818:Animals; D002247:Carbon Isotopes; D002952:Citric Acid Cycle; D005260:Female; D005649:Fumarate Hydratase / Q000378:metabolism; D005947:Glucose / Q000096:biosynthesis* / Q000737:chemistry; D005986:Glyceraldehyde 3-Phosphate / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008954:Models, Biological; D011766:Pyruvate Carboxylase / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013389:Succinate-CoA Ligases / Q000378:metabolism
D002247:Carbon Isotopes; D011768:Pyruvate Dehydrogenase Complex; D005986:Glyceraldehyde 3-Phosphate; D019289:Pyruvic Acid; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D013385:Succinate Dehydrogenase; D005649:Fumarate Hydratase; D013389:Succinate-CoA Ligases; D011766:Pyruvate Carboxylase; D005947:Glucose