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.(ABSTRACT TRUNCATED AT 250 WORDS)
Hellerstein
M K
MK
USDA Human Nutrition Research Center on Aging at Tufts, Boston, MA 02111.
Munro
H N
HN
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002250:Carbon Radioisotopes; D005690:Galactose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium; D014534:UDPglucose 4-Epimerase / Q000502:physiology; D014532:Uridine Diphosphate Glucose / Q000378:metabolism
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D014316:Tritium; D014534:UDPglucose 4-Epimerase; D005947:Glucose; D014532:Uridine Diphosphate Glucose; D005690:Galactose