Galactose and glucose metabolism in the isolated perfused suckling and adult rat liver

Berman, Wallace F.; Rogers, Shirley; Bautista, Jesusa O.; Segal, Stanton

doi:10.1016/0026-0495(78)90258-5

Cited by 26 publications

(15 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The utilization by suckling cells at each time point studied was again about 4-fold higher than the adult cells. These curves for 4 mM galactose uptake differed from those found previously with perfused rat liver (2). In the perfused suckling liver, there was a 30 min lag before the onset of a linear rate, whereas in the perfused adult liver the curve was linear through the origin (2).…”

Section: Resultscontrasting

confidence: 90%

“…In order to more precisely learn the details of galactose uptake and conversion to glucose-by suckling rat livers,-we have recently utilized the isolated liver perfusion technique (3,22). A comparison of isolated perfused livers of suckling and adult rats revealed that the liver of the suckling rat not only took up more galactose from the perfusate than the adult, but put out proportionately larger amounts of glucose (2). Indeed, over 80% of perfused galactose was converted to glucose by livers of suckling animals (3).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Galactose Metabolism in Suckling and Adult Isolated Rat Hepatocytes

1983

Self Cite

View full text Add to dashboard Cite

SummaryThe metabolism of galactose during the postnatal developmental period has been examined in isolated parenchymal cells of livers from fasted rats aged 7, 14,21,28, and 42 days, by measuring the disappearance of 1 and 4 mM l- [14C]galactose from the incubation media as well as [14C]galactose conversion to [14C]glucose and ['4C]lactate and oxidation to [14COz]. Cells from 7-and 14-day-old suckling animals consistently utilized galactose more rapidly (4 times greater) than those of adult. Hepatocytes of suckling rats also converted greater amounts of galactose to glucose and oxidized galactose 2-3 times faster than the adult. The conversion to glucose by suckling cells occurred with minor recycling of labeled C-1 galactose to C-6 of glucose. A comparison with [l-14C]glucose as substrate showed that oxidative rates by the young cells were 3 times faster for galactose than for glucose. This was not due to the presence of a direct galactose oxidative pathway as assessed by the [l4COZ] yield from C-1 and C-2 labeled galactose. Incubation of hepatocytes with galactose appeared to augment the production of glucose from endogenous precursors, 33 nmoles/mg cells in 30 min. The enhanced glucose output from endogenous sources in isolated suckling hepatocytes incubated with galactose contrasts with the sugar's suppression of glucose output observed in isolated perfused liver even though galactose metabolism in both preparations are similarly greater in the suckling than in the adult. Abbreviations KRB, Krebs-Ringer bicarbonate KRB-A, Krebs-Ringer bicarbonate containing 3% albumin LDH, L-lactic dehydrogenaseIn the young mammal, galactose is an important dietary carbohydrate. Because the liver is the major organ involved in the metabolism of galactose (34), our laboratory has focused on the mechanism whereby this hepatic process occurs. Past developmental analyses of rat liver galactokinase (lo), galactose-l-phosphate uridyltransferase (5), and uridine diphosphogalactose-4-epimerase (9) (the major enzymes of galactose disposition), indicated their specific activity to be maximal during the suckling period. In order to more precisely learn the details of galactose uptake and conversion to glucose-by suckling rat livers,-we have recently utilized the isolated liver perfusion technique (3,22). A comparison of isolated perfused livers of suckling and adult rats revealed that the liver of the suckling rat not only took up more galactose from the perfusate than the adult, but put out proportionately larger amounts of glucose (2). Indeed, over 80% of perfused galactose was converted to glucose by livers of suckling animals (3).Whereas the isolated perfused liver has been extensively used as a physiologic model system to study metabolic processes (13, 15, 39), isolated hepatocytes have become a tool used to promote evaluation at the cellular level and to augment results obtained with the intact organ system (1,19,38): The use of the hepatocyte preparation eliminates the metabolic contribution of other hepatic cellular elements, f...

show abstract

Section: Resultscontrasting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Galactose Metabolism in Suckling and Adult Isolated Rat Hepatocytes

1983

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast, galactokinase and transferase sp act are programmed to increase to a maximum at about 8 days of age and then diminish to adult levels. Galactose metabolic studies of minced liver (22) with suckling rat hepatocytes (23) and perfused liver (24) show that young liver has a greater ability to metabolize galactose than adult tissue, thus giving functional significance to the high enzyme activities observed during the suckling period when galactose is ingested.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 1989

Self Cite

View full text Add to dashboard Cite

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...

show abstract

“…The newborn liver converts galactose to glucose-1-phosphate faster in the suckling period than the adult period (21)(22)(23)(24)(25). The actual rate-limiting step in the hepatic clearance of galactose is thought to be one of the enzymes of the Leloir pathway (26,27), although there is some evidence to suggest it may be hepatic membrane transport of hexoses that is rate limiting (24). We have shown in lambs that the hepatic capacity to clear galactose from the portal venous circulation in the unstressed, postprandial state is exceeded when the portal vein galactose concentration is more than 10-12 mg/dl.…”

Section: Discussionmentioning

confidence: 99%

Galactose, Glucose, and Lactate Concentrations in the Portal Venous and Arterial Circulations of Newborn Lambs after Nursing

Kaempf

Groothuis

et al. 1988

Pediatr Res

View full text Add to dashboard Cite

Lactose is a carbohydrate with several unique and intriguing characteristics. It is the sole dietary carbohydrate of nearly all newborn mammals, and except in humans, is consumed exclusively in the neonatal period. Galactose, one of its component monosaccharides, is not an important substrate in the fetus (1) but can represent up to 20% of the caloric intake of the neonate (2). Despite the importance of lactose and galactose in the newborn diet, their neonatal metabolism is incompletely understood.Recently, we have described the postprandial change in galactose and glucose concentrations in the peripheral blood of newborn infants seen after a single milk feeding (3). There was a striking difference in the metabolism of the two carbohydrates. To investigate this phenomenon in more depth, our study was camed out in newborn lambs with chronic indwelling catheters placed in the portal venous and arterial circulations. Thus, lactose metabolism could be studied in an unstressed, newborn mammal immediately after a milk feeding. METHODSAll lambs were of mixed Western breed, delivered spontaneously at term, and were in good health. They nursed solely from their mothers. Within the first 10 days of life the lambs were given general anesthesia with pentobarbital (30 mg/kg) and local lidocaine. One polyvinyl catheter (0.054 in OD, 0.034 in ID) was placed in the portal vein via an umbilical vein cutdown. A second catheter was placed in the femoral artery. The catheters were tunneled subcutaneously, exteriorized, and kept in a small side pouch for access. Penicillin (300,000 U) and streptomycin (0.5 g) were given intramuscularly on the day of surgery only. Care was taken to wash the surgical area free of betadine after surgery to facilitate acceptance by the lamb's mother. All lambs were allowed to recover with their mothers for a minimum of 48 h. No lamb lost weight and all were observed to be vigorous, nursing normally, and gaining weight at the time of the first study. Catheters were flushed every other day with heparin 100 U/ml. Catheter tip placement was confirmed at autopsy.On the day of study the lambs were separated from their mothers and fasted for 5 h to ensure that the stomach and small intestine were empty of milk. At time 0 the lambs were weighed and baseline blood samples were drawn from the portal vein and femoral artery. The lambs were then allowed to nurse ad libitum from their mothers for 20 min and were weighed again to determine milk intake. There were no urine or stool losses during this 20-min period. At times 30, 40, 60, 80, 100, 120, 140, 160, 190, and 220 min after beginning nursing, samples were drawn from the portal vein and femoral artery catheters while the lambs rested quietly. Twenty-five studies were done on 1 1 lambs. Chemical analyses. Concentrations of D-galactose, D-glucose,and L-lactate were measured on each whole blood sample. DGalactose was determined by the galactose oxidase method described by Hjelm and deverdier (4). D-Glucose and L-lactate concentrations were determined using analyz...

show abstract

Galactose and glucose metabolism in the isolated perfused suckling and adult rat liver

Cited by 26 publications

References 36 publications

Galactose Metabolism in Suckling and Adult Isolated Rat Hepatocytes

Galactose Metabolism in Suckling and Adult Isolated Rat Hepatocytes

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

Galactose, Glucose, and Lactate Concentrations in the Portal Venous and Arterial Circulations of Newborn Lambs after Nursing

Contact Info

Product

Resources

About