D‐galactose Transport by Synaptosomes Isolated From Rat Brain

Warfield, Anna S.; Segal, Stanton

doi:10.1111/j.1471-4159.1974.tb12211.x

Cited by 29 publications

(14 citation statements)

References 35 publications

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“…Litters were reduced to seven on the day of delivery, and young rats were weaned onto their respective maternal diets at 19 days of age. Synaptosomes were isolated as described (8). For young rats, modified Ficoll gradients were used.…”

Section: Methodsmentioning

confidence: 99%

Myoinositol and phosphatidylinositol metabolism in synaptosomes from galactose-fed rats.

Warfield¹,

Segal²

1978

Proc. Natl. Acad. Sci. U.S.A.

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The effects of experimental galactose toxicity on inositol and phosphatidylinositol (PtdIns) metabolism in synaptosomes from 0-to 30day-old rats were investigated. Galactose toxicity was induced by feeding mothers a 40% galactose diet from the 12th day of pregnancy until 19 days postpartum when the offspring were weaned onto the maternal diet. There was no decrease in myoinositol concentrations and only a small decrease in PtdIns in synaptosomes from galactose-fed rats relative to glucose-fed controls. Synaptosomes from rats on the two diets converted equivalent amounts of [ U-14Clglucose to inositol and PtdIns. Acetylcholine stimulated [2-MlHinositol incorporation into PtdIns while producing a net decrease in Ptdlns concentration in synaptosomes from 22-to 30-day-old rats. However, the phospholipid response to acetylcholine in synaptosomes from galactose-fed rats was impaired. Thus, the acetylcholine-stimulated labeling of PtdIns was 40-50% lower in these synaptosomes while the effect on Ptdlns concentration was reduced by a maximum of 55%. The data suggest that galactose-fed rats may have either a deficiency in the number of acetylcholine receptors or a defect in some step between receptor-neurotransmitter interaction and PtdIns breakdown.Since mental retardation appears to be the only incompletely reversible outcome of galactosemia caused by deficiency of the enzyme, galactose-1-phosphate uridylyltransferase, much interest has centered around the cause of the neurotoxicity. Wells and coworkers (1, 2) have reported increased concentrations of galactose and galactitol and a decrease in the concentration of free and lipid-bound myoinositol (Ins) in brain and nerve tissue of several galactosemic infants, and Schwarz (3) has demonstrated an increased concentration of galactose-1-phosphate in the nervous system of such patients. However, the mechanism by which galactose or its metabolites exert their toxic effects on the developing nervous system remains to be elucidated.In rats and chickens, experimental galactose toxicity results in decreased brain development, decreased nerve conduction, and decreased concentrations of glucose and of free amino acids in brain and nerve tissues (4). Wells and Wells (5) reported elevation of galactitol concentration and depression of free and lipid-bound Ins concentrations in brains of developing rats whose mothers were maintained on high galactose diets throughout pregnancy and lactation. In addition, these investigators demonstrated a decrease in the ability of brain slices from young galactose-toxic rats to convert [14C]glucose to Ins or phosphatidylinositol (PtdIns). Kozak and Wells (6) demonstrated decreased labeling of phosphatidic acid (PtdA) and PtdIns in brains of galactose-toxic chickens after intracranial injection of 32P1, although no change in total amount of phospholipid phosphorus was observed.These observations suggesting an impairment in Ins and Ins phospholipid synthesis or metabolism in galactose-toxic animals are of special significance in view of the e...

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Section: Methodsmentioning

confidence: 99%

Myoinositol and phosphatidylinositol metabolism in synaptosomes from galactose-fed rats.

Warfield¹,

Segal²

1978

Proc. Natl. Acad. Sci. U.S.A.

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“…When the gray and white matters were compared, higher radioactivity was found in the gray matter, which was also higher in mice after [U-14C]glucose injection (44). Warfield et al (54) reported that the brain of rat and chick had the Leloir pathway, but the activities of transferase (34) and UDP-galactose-4-epimerase (7) which catalyze the conversion of UDP-galactose to UDP-glucose, were low in the brain.…”

Section: R-mentioning

confidence: 99%

“…After this period, activities of these enzymes decrease and the epimerase attains adult level at 20 days after birth, but the galactokinase and transferase at 35 days (2). In the adult animals, galactose may also be utilized as an energy source in certain organs such as the kidney (27,33,39,51), small intestine (36), brain (34,47,54) and myocardium (34).…”

Section: Distributionmentioning

confidence: 99%

Whole-body autoradiographic study on the distribution of (U-14C)galactose in adult, pregnant, newborn and infant mice.

Shimono

1984

Acta Histochem. Cytochem

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“…Galactose can be taken up into the brain across the blood-brain barrier by the same carrier mechanism of glucose (7,9,24). The presence of the enzymes of the Leloir pathway in rat and chick brain has been well documented (3,5,8,19,40). On the other hand, low galactose-1-P uridyltransferase activity in the rat brain has been reported by Musick et al (21).…”

Section: Discussionmentioning

confidence: 90%

“…It is generally accepted that galactose is conveyed to the liver, where it is converted to glucose by the Leloir pathway (18). In the previous studies, enzyme activities belonging to this pathway have been found in the liver (3, 5, 8, 33), kidney (3, 5, 8, 16, 20, 25, 34), intestine (23), brain (21,32,40) and myocardium (21) etc. On the other hand, it has been reported that galactose is an important constituent of the glycoproteins, glycolipids and mucopolysaccharides (1,4,10,13,14,15,22).…”

mentioning

confidence: 99%

Whole-body autoradiographic study of (U-14C) galactose in mice and its biochemical analysis.

Shimono

1985

Acta Histochem. Cytochem

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Tissue and organ distribution and metabolic fate of radioactive carbon from [U-14C] galactose in mice were studied by whole-body autoradiography and biochemical analysis.Autoradiography was performed before and after 6 % perchloric acid treatment at various intervals after intravenous injection of [U-14C] galactose. At 5 min after injection, high radioactivities were observed in the kidney, small intestine and liver.The radioactivities in almost all organs were markedly decreased with the acid treatment.At 30 min after injection, the kidney and small intestine had relatively high radioactivities which were retained by the acid treatment.As for the biochemical analysis, at various intervals after intravenous injection of [U-14C] galactose, the mice were decapitated, and the blood, liver, kidney, small and large intestines, myocardium and brain were removed. These organs were fractionized into 6 % perchloric acid-soluble, -insoluble and lipid parts.Total radioactivity (cpm) per gram of wet weight was the highest in the kidney.The incorporation rates of the radioactivity into the acid-soluble fraction were high in all organs at early intervals, while at late intervals, the rates into the acid-insoluble fraction became relatively high in the kidney, small and large intestines.These results were consistent with those obtained from whole-body autoradiography.Acid-soluble fractions of the blood, kidney, liver and brain were analyzed by paper chromatography.The radioactive spots for galactose and glucose were observed in all organs examined, but the changes of radioactive values with the passage of time were different in each organ.Furthermore, the radioactive spots for RGlucose value 0.28 were detected in these organs.Galactose is C-4 epimer of glucose and is derived from lactose. Ingested lactose is absorbed in the small intestine and then hydrolyzed by 3-galactosidase (lactase) into glucose and galactose. It is generally accepted that galactose is conveyed to the liver, where it is converted to glucose by the Leloir pathway (18). In the previous studies, enzyme activities belonging to this pathway have been found in the liver (3, 5, 8, 33), kidney (3, 5, 8, 16, 20, 25, 34), intestine (23), brain (21,32,40) and myocardium (21) etc. On the other hand, it has been reported that galactose is an important constituent of the glycoproteins, glycolipids and mucopolysaccharides (1,4,10,13,14,15,22).

show abstract

D‐galactose Transport by Synaptosomes Isolated From Rat Brain

Cited by 29 publications

References 35 publications

Myoinositol and phosphatidylinositol metabolism in synaptosomes from galactose-fed rats.

Myoinositol and phosphatidylinositol metabolism in synaptosomes from galactose-fed rats.

Whole-body autoradiographic study on the distribution of (U-14C)galactose in adult, pregnant, newborn and infant mice.

Whole-body autoradiographic study of (U-14C) galactose in mice and its biochemical analysis.

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