Noninvasive tracing of Krebs cycle metabolism in liver
- Karolinska Institute, (Sweden)
To quantify intrahepatic Krebs cycle metabolism, phenyl acetate, excreted in urine as a glutamine conjugate, was given to healthy subjects infused with (3-14C)lactate. They were studied after 60 h of fasting and when given glucose after an overnight fast. Distributions of 14C in glutamate from urinary phenylacetylglutamine and blood glucose were determined. Corrections to the distributions because of the fixation of 14CO2 formed from the (3-14C)lactate were determined by administering (14C)bicarbonate. Comparisons of distributions in glucose and glutamate support the assumption that the glutamate distributions reflect those in hepatic alpha-ketoglutarate. From the distributions in glutamate, the extent of exchange of labeled with unlabeled carbons and relative flow rates in the cycle in liver were estimated. Dilution of 14C by 12C in the cycle was found in the fasted but not the fed state. In the fasted state, pyruvate carboxylation was estimated to be at least twice the rate of Krebs cycle flux and the rate of pyruvate's decarboxylation less than 1/25 the rate of its carboxylation. In the fed state, the rate of decarboxylation was estimated to be between one-sixth and one-half the rate of carboxylation. The rate of conversion of oxalacetate to fumarate in both states appeared to be greater than 6 times the rate of Krebs cycle flux.
- OSTI ID:
- 5801631
- Journal Information:
- Journal of Biological Chemistry; (USA), Journal Name: Journal of Biological Chemistry; (USA) Vol. 266:11; ISSN JBCHA; ISSN 0021-9258
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ACETATES
ALDEHYDES
AMIDES
AMINO ACIDS
BODY
CARBOHYDRATES
CARBON 12
CARBON 14 COMPOUNDS
CARBON ISOTOPES
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACID SALTS
CARBOXYLIC ACIDS
DIGESTIVE SYSTEM
EVEN-EVEN NUCLEI
FASTING
GLANDS
GLUCOSE
GLUTAMIC ACID
HEXOSES
ISOTOPE APPLICATIONS
ISOTOPE DILUTION
ISOTOPES
LABELLED COMPOUNDS
LACTATES
LIGHT NUCLEI
LIVER
MATHEMATICAL MODELS
METABOLISM
MONOSACCHARIDES
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
SACCHARIDES
STABLE ISOTOPES
TRACER TECHNIQUES
UREA