Metabolic pathways for ketone body production. /sup 13/C NMR spectroscopy of rat liver in vivo using /sup 13/C-multilabeled fatty acids
The hormonal regulation of ketogenesis in the liver of living rat has been studied noninvasively with /sup 13/C nuclear magnetic resonance. The spatial selection for the liver was better than 90%, with extrahepatic adipose tissue contribution only a very small amount of signal. The metabolic activities of the liver were investigated by infusion of /sup 13/C-labeled butyrate in the jugular vein of the anesthetized rat. The rate of butyrate infusion was chosen to be close to the maximum oxidative capacity of the rat liver, and the /sup 13/C signal intensities were enhanced by using doubly labeled (1,3-/sup 13/C)butyrate as a substrate. Different /sup 13/C NMR spectra and hence different metabolites were observed depending on the hormonal state of the animal. The /sup 13/C NMR studies demonstrate that even when rate of acetyl-CoA production are high, the disposal of this compound is not identical in fasted and diabetic animals. This supports previous suggestions that the redox state of the mitochondrion represents the most important factor in regulation. For a given metabolic state of the animal, different signal intensities were obtained depending on whether butyrate was labeled at C-1, C-3, or C-1,3. From the ratios of incorporation of /sup 13/C label into the carbons of 3-hydroxybutyrate, it could be estimated that a large fraction of butyrate evaded ..beta..-oxidation to acetyl-CoA but was converted directly to acetoacetyl-CoA. /sup 13/C-labeled glucose could be detected in vivo in the liver of diabetic rats.
- Research Organization:
- Biocenter of the Univ. of Basel, Switzerland
- OSTI ID:
- 6549158
- Journal Information:
- Biochemistry; (United States), Vol. 25:22
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
KETONES
BIOSYNTHESIS
NMR SPECTRA
LABELLED COMPOUNDS
LIVER
BIOLOGICAL PATHWAYS
BUTYRIC ACID
CARBON 13
CARBOXYLIC ACIDS
COENZYMES
NUTRITIONAL DEFICIENCY
RATS
ANIMALS
BODY
CARBON ISOTOPES
DIGESTIVE SYSTEM
EVEN-ODD NUCLEI
GLANDS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MONOCARBOXYLIC ACIDS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RODENTS
SPECTRA
STABLE ISOTOPES
SYNTHESIS
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics
550201 - Biochemistry- Tracer Techniques