/sup 13/C NMR study of effects of fasting and diabetes on the metabolism of pyruvate in the tricarboxylic acid cycle and of the utilization of pyruvate and ethanol in lipogenesis in perfused rat liver
/sup 13/C NMR has been used to study the competition of pyruvate dehydrogenase with pyruvate carboxylase for entry of pyruvate into the tricarboxylic acid (TCA) cycle in perfused liver from streptozotocin-diabetic and normal donor rats. The relative proportion of pyruvate entering the TCA cycle by these two routes was estimated from the /sup 13/C enrichments at the individual carbons of glutamate when (3-/sup 13/C)alanine was the only exogenous substrate present. In this way, the proportion of pyruvate entering by the pyruvate dehydrogenase route relative to the pyruvate carboxylase route was determined to be 1:1.2 +/- 0.1 in liver from fed controls, 1:7.7 +/- 2 in liver from 24-fasted controls, and 1:2.6 +/- 0.3 in diabetic liver. Pursuant to this observation that conversion of pyruvate to acetyl coenzyme A (acetyl-CoA) was greatest in perfused liver from fed controls, the incorporation of /sup 13/C label into fatty acids was monitored in this liver preparation. With the exception of the repeating methylene carbons, fatty acyl carbons labeled by (1-/sup 13/C)acetyl-CoA (from (2-/sup 13/C)pyruvate) gave rise to resonances distinguishable on the basis of chemical shift from those observed when label was introduced by (3-/sup 13/C)alanine plus (2-/sup 13/C)ethanol, which are converted to (2-/sup 13/C)acetyl-CoA. Thus, measurement of /sup 13/C enrichment at several specific sites in the fatty acyl chains in time-resolved spectra of perfused liver offers a novel way of monitoring the kinetics of the biosynthesis of fatty acids. In addition to obtaining the rate of lipogenesis, it was possible to distinguish the contributions of chain elongation from those of the de novo synthesis pathway and to estimate the average chain length of the /sup 13/C-labeled fatty acids produced.
- Research Organization:
- Merck Sharp and Dohme Research Labs., Rahway, NJ
- OSTI ID:
- 6790553
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:2; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ALCOHOLS
ANIMAL TISSUES
ANIMALS
BIOCHEMISTRY
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
BIOSYNTHESIS
BODY
CARBON 13
CARBON ISOTOPES
CARBOXYLIC ACIDS
CHEMISTRY
DIABETES MELLITUS
DIGESTIVE SYSTEM
DISEASES
ENDOCRINE DISEASES
ENZYMES
ETHANOL
EVEN-ODD NUCLEI
FASTING
GLANDS
HEMIACETAL DEHYDROGENASES
HYDROXY COMPOUNDS
ISOTOPES
KETO ACIDS
LABELLED COMPOUNDS
LIGHT NUCLEI
LIPIDS
LIVER
MAGNETIC RESONANCE
MAMMALS
METABOLIC DISEASES
METABOLISM
NUCLEAR MAGNETIC RESONANCE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PERFUSED TISSUES
PHOSPHORUS 31
PHOSPHORUS ISOTOPES
PYRUVIC ACID
RATS
RESONANCE
RODENTS
STABLE ISOTOPES
SYNTHESIS
TISSUES
VERTEBRATES