Activity of Hepatic Galactose-Metabolizing Enzymes in the Pregnant Rat and Fetus

Abstract

ABSTRACT. The sp act of hepatic galactose-metabolizing enzymes, galactokinase, galactose-1-phosphate uridyltransferase, and uridine diphosphate-4-epimerase were measured in female rats during pregnancy and lactation as well as in fetuses and pups after parturition. S p act for transferase and epimerase in pregnant rat liver are about 50% higher than that of virgin females, and with the increase in organ size during pregnancy the total hepatic activity is double that of nonpregnant animals. Galactokinase activity decreases somewhat during pregnancy, but total activity is 25% higher than in virgin liver. A Michaelis-Menten kinetic analysis of liver transferase indicates an increase in the maximum velocity of the reaction without a change in Km. Isoelectricfocusing on a high-resolution IEF gel demonstrated similar isozyme patterns. The sp act of the fetal liver enzymes increase to about twice that of the maternal tissue, but total activities are low due to the very small fetal liver size. Sp act of these enzymes in maternal liver fall after delivery, but sp act of galactokinase and transferase are programmed to increase in liver of the growing neonatal animals, reaching levels almost 5-fold higher than found in nonpregnant adult liver. An understanding of factors contributing to the enhanced transferase activity of the liver of pregnant and neonatal rats may contribute to possible ways of augmenting the residual transferase activitv of ~atients with transferase-deficient galactosemia as therapeutic strategy. (Pediatr Res 25:161-166, 1989) Abbreviations Galactokinase, (EC 2.7.16) Transferase, galactose-1-phosphate uridyltransferase (EC 2.7.7.12) Epimerase, uridine diphosphate galactose-4-epimerase (EC 5.1.32) UDPglucose, uridine 5'-diphosphoglucose Galactose-1-P, a-D-galactose-1-phosphate IEF, isoelectric focusingThe feeding of a high galactose-containing diet to pregnant rats has been used as a model to study in utero galactose toxicity in the fetus and newborn (1, 2). The focus of such research has centered mainly on neonatal toxicity with little regard for galactose effect on the pregnant mothers. Several pertinent findings, however, have been made indicating galactose metabolism may be different in pregnant animals. We have observed that cataracts do not develop in pregnant rats fed a high galactose diet for the 21 days of gestation, whereas they are found in young male rats fed the same diet for the same number of days (2, 3). Others have reported that pregnant rat lenses are clear until 48 h after parturition when cataractous changes precipitously appear (4). These data suggest that pregnancy affords protection of the female from galactose toxicity. Although extensive investigations of glucose metabolism have been made in the pregnant rat (5-7), little is known about galactose metabolism in the gestational state. Therefore, we have examined the sp act of the galactosemetabolizing enzymes galactokinase, transferase, and epimerase in the liver of dams throughout pregnancy and lactation and in the fetus for c...

Developmental and Tissue-Specific Modulation of Rat Galactose-1-Phosphate Uridyltransferase Steady State Messenger RNA and Specific Activity Levels

“…Modulation of GALT specific enzyme activity mirrors that of GALT mRNA. The developmental pattern in GALT sp act found in this study is similar to that reported previously (3,5).…”

“…GALT mRNA data represent areas obtained from densitometric analysis of the autoradiogram shown in Figure I. GALT sp act was measured on the same samples except d 9 and 15 were measured instead of d 10 and 14 and d I values were as previously reported (3). Data represent the mean of n = 3 or 4.…”

“…rncluszlrcJrncn(. GALT specific enzyme activity during development was measured on the same specimens as GALT mRNA with the exception of d I , 10, and 14; instead rat livers from d 9 and 15 were determined and d 1 values were as previously reported (3). Measurement of sp act in adult rat tissues was performed on the same specimens used for RNA isolation with the exception of the ovary.…”

“…Measurement of sp act in adult rat tissues was performed on the same specimens used for RNA isolation with the exception of the ovary. where published values are used (3). The measurement of GALT activity in the newborn rat liver and in the adult rat tissue specimens was based on the radioisotope method of Betoli and Segal (5).…”

Developmental Regulation of Galactokinase in Suckling Mouse Liver by the Egr-1 Transcription Factor

“…Liver galactokinase activity is known to increase approximately 5-fold during neonatal life in the rodent (24). To determine whether galactokinase expression was regulated at the level of mRNA abundance, we examined its developmental expression pattern by reprobing the same Northern blot used for Egr-1.…”