Glycoconjugates as noninvasive probes of intrahepatic metabolism. III. Application to galactose assimilation by the intact rat
A tracer methodology has been developed for noninvasive assessment of intrahepatic metabolism of administered labeled sugars. In this procedure, we measure the output of the label from the liver in two glycoconjugates derived from hepatic UDP-glucose, namely, glucuronic acid formed through UDP-glucuronic acid and excreted in the urine following acetaminophen administration, and galactose formed through UDP-galactose and then secreted in the carbohydrate portion of glycoproteins in the plasma. Comparison of the distribution of label from various sugar precursors in these end-products can indicate exchanges between hepatic UDP-glucose, UDP-galactose, and UDP-glucuronic acid. In this study we apply the technique to explore whether the enzyme UDP-galactose-4-epimerase catalyzing the step UDP-galactose to UDP-glucose is nonequilibrium and therefore potentially has a regulatory role for utilization of free galactose. The specific activity in the two glycoconjugates was compared when either (1-3H)galactose or (U-14C)glucose was the infused precursor sugar. In rats under a variety of conditions (fasting, oral refeeding, intravenous administration of galactose), label from (1-3H)galactose accumulated in glycoprotein-bound galactose much more than in acetaminophen-bound glucuronic acid, in comparison to label from (U-14C)glucose, demonstrating limitation of the rate of transfer from UDP-galactose to UDP-glucose at the epimerase step. Accordingly, epimerase is suggested to have a regulatory role in the galactose assimilation pathway.
- Research Organization:
- USDA Human Nutrition Research Center on Aging at Tufts, Boston, MA (USA)
- OSTI ID:
- 7191433
- Journal Information:
- Metab., Clin. Exp.; (United States), Vol. 37:4
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
GALACTOSE
BIOSYNTHESIS
GLUCOSE
METABOLISM
CARBON 14 COMPOUNDS
GLUCURONIC ACID
LIVER
RATS
SECRETION
TRACER TECHNIQUES
TRANSFERASES
TRITIUM COMPOUNDS
ALDEHYDES
ANIMALS
BODY
CARBOHYDRATES
CARBOXYLIC ACIDS
DIGESTIVE SYSTEM
ENZYMES
GLANDS
HEXOSES
HYDROXY ACIDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MONOSACCHARIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RODENTS
SACCHARIDES
SYNTHESIS
VERTEBRATES
550501* - Metabolism- Tracer Techniques