Decreased preference for sucrose in rats fed a low protein diet and its intensification by zinc-deficiency.

This study examined whether protein concentrations in the diet of rats fed adequate Zn or deficient Zn affect their preference for disaccharides of sucrose and maltose. Sucrose and maltose were used as a source of carbohydrate and the selection patterns of rats were analyzed for 28 d by a two-choice selection method. Diets provided as a set of two either Zn-adequate or Zn-deficient diets containing 10, 20 and 40% protein each were changed in position daily. For the first 24 h, both the control Zn-adequate and Zn-deficient rats preferred sucrose to maltose and then gradually selected the maltose diet. Protein in the diet affected the selection of the disaccharides for both the control and Zn-deficient rats. The decrease order of the ratio of consumed sucrose to maltose over 28 d was 10% > 20% > 40% protein diet group, and Zn-deficiency emphasized the decrease. These results suggest that sucrose has a stronger taste effect than maltose in rats, but that the selection of sucrose is decreased by the post-ingestive effect which is stimulated in low-protein and Zn-deficient diets.

Change to a preference for maltose from sucrose over days in Zn-deficient rats selecting from maltose and sucrose diets.

This paper describes a preference for two disaccharides in the diets of Zn-adequate and Zn-deficient rats. Maltose and sucrose were used as a source of carbohydrate in the diet and the selection patterns of rats were analyzed for 28 d by a two-choice selection method. Diets provided as a set of two either Zn-adequate or Zn-deficient diets were changed in position daily. Control Zn-adequate and Zn-deficient rats both exclusively selected the sucrose diet at days 1 and 2, after onset of the feeding experiment, and then gradually selected the maltose-diet. After changing their preference from sucrose to maltose, the Zn-adequate control rats selected widely from both the maltose and sucrose diets, while the Zn-deficient rats exclusively and continuously selected the maltose diet from the two diets over the experimental period. The level of selection of sucrose-diet on day 28 had a correlation with the intestinal sucrase activity in the control rats. The sum of daily maltose and sucrose diet intake in rats fed a Zn-deficient diet showed a characteristic variation with the cyclic period of 3.6+/-0.2 d. The daily body-weight change of rats fed a Zn-deficient diet was well synchronized with their own food intake cycle. The day before changing preference from sucrose to maltose in rats fed a Zn-deficient diet represented a trough in their own food intake and body-weight cycles. These results suggest that one sign of a change in preference from sucrose to maltose in Zn-deficient rats is caused by a stage of negative energy balance.

Modulation of maltose preference by selection from dextrin, maltose and glucose diets in zinc-deficient rats.

This study examined whether the chain length of glucose in the diet could affect the selection of foods by Zn-adequate and Zn-deficient rats. Dextrin, maltose and glucose were used as sources of carbohydrate in the diet and the selection patterns of the rats were analyzed for 28 d by a 3-choice selection. Diets provided as a set of three either Zn-adequate or Zn-deficient diets were rotated daily. The Zn-adequate control rats selected widely from the three diets throughout the 28 d. In contrast, rats fed a Zn-deficient diet selected exclusively and continuously the dextrin diet or dextrin and glucose diets from the three diets over the experimental periods. The average daily total food intakes of rats fed a Zn-deficient diet were very significantly decreased. The selections of dextrin, maltose and glucose diets in the 3-choice methods of the control rats were 5.7+/-1.6(b), 5.8+/-2.0(b) and 2.7+/-0.9(a) g/d, respectively (p<0.05), and those of the Zn-deficient rats were 6.4+/-2.5(c), 0.8+/-1.3(a) and 2.6+/-1.4(b) g/d, respectively (p<0.05). The ratios of the selected maltose-diet in the Zn-adequate control and the Zn-deficient rats were 40.8+/-13.8 and 9.0+/-15.6%, respectively (p<0.01) and those of the dextrin-diet were 40.3+/-11.4 and 63.0+/-22.3%, respectively (p<0.05). The decreased preference for the maltose-diet in the Zn-deficient rats may reflect the increased selection of the dextrin-diet.

Mechanism of liver tyrosine aminotransferase increase in ethanol-treated mice and its effect on serum tyrosine level.

Liver tyrosine aminotransferase (TAT) activity is known to increase with ethanol treatment; however, the mechanism of this increase is unclear. Upon investigation we found that TAT activity and mRNA levels started to increase 2 h after ethanol administration and continued to increase until 6 h after ethanol administration. The increase in ethanol-induced TAT activity could not be explained by calorie loading after fasting, since ethanol loading increased TAT expression, while glucose loading decreased TAT expression. In addition, liver TAT activity was not related to serum tyrosine levels. TAT activity increased when an adenosine A2 agonist, 5'-N-ethylcarboxamide adenosine, was given. Since TAT activity is increased by cAMP, and ethanol increases cAMP production via an adenosine receptor-dependent mechanism, this increase in ethanol-induced TAT activity may occur via an adenosine receptor-dependent mechanism.

Effect of fasting on methionine adenosyltransferase expression and the methionine cycle in the mouse liver.

The effect of fasting on mouse liver methionine adenosyltransferase (MAT I/ III) expression and the regulation of methionine metabolism were investigated. The mRNA level, protein level, and activity of MAT I/III were increased by fasting for 10 or 16 h. In spite of the increase of MAT I/III activity, S-adenosylmethionine, the product of methionine due to MAT I/III, decreased. S-Adenosylhomocysteine, which is made from S-adenosylmethionine by its coupling to methyltransferase, increased as a result of fasting for 16 h. These results suggest that the total methylation reactions using S-adenosylmethionine are stimulated in the fasting mouse liver. However, the DNA methylation level was not changed by fasting for 16 h. Glutathione, which is made by the transsulfuration pathway from homocysteine, decreased due to fasting. Regulation of supplementation of S-adenosylmethionine may occur in the fasting mouse because MAT I/III activity increases and the flow to glutathione is decreased.

Preference for glucose in Zn-deficient rats selecting from glucose and fructose diets.

Glucose and fructose selection patters of rats were analyzed for 28 d by a 2-choice selection in either Zn-adequate or Zn-deficient status. In this paper, we describe the following serial studies: (1) For the first 24 h, rats fed a Zn-deficient diet preferred a fructose-diet compared with a glucose-diet. On and after the third day, rats fed both Zn-adequate and Zn-deficient diets preferred the glucose-diet. (2) Throughout the experimental period, many of the rats fed a Zn-adequate and Zn-deficient diet continuously selected one diet. (3) Some of the rats fed a Zn-adequate and Zn-deficient diet suddenly changed preference for the glucose-diet or the fructose-diet. (4) The sum of daily glucose- and fructose-diet intake in rats fed a Zn-deficient diet showed a characteristic variation with the cyclic period of 3.9 +/- 0.4 d.

Purification and expression of a processing protease on beta-alanine-oxoglutarate aminotransferase from rat liver mitochondria.

GABA[arrow beta]AlaAT convertase is an endopeptidase that processes brain-type 4-aminobutyrate aminotransferase (GABA AT; EC 2.6.1.19) to liver-type beta-alanine-oxoglutarate aminotransferase (beta-AlaAT I) in rats. Its molecular mass was 180 kDa as determined by gel filtration. A subunit molecular mass of 97652 Da was measured using MALDI-TOF MS. The N-terminal sequence of the purified GABA[arrow beta]AlaAT convertase was SRVEVSKVLILGSGGLSIGQAGEFDYSGSQAV- and was identical to residues 418-449 of carbamoyl-phosphate synthetase I (CPS I; EC 1.2.1.27) purified from rat liver. The subunit molecular mass and the N-terminal amino acid sequence suggested that GABA[arrow beta]AlaAT convertase was the 418-1305 peptide of CPS I. An expression vector containing the coding region of the 418-1305 peptide of rat CPS I was transfected into NIH3T3 cells and the extract of the cells showed GABA[arrow beta]AlaAT convertase activity.

The influence of various carbohydrates on the feeding pattern of rats fed zinc-deficient diets.

When dextrin, maltose, sucrose, glucose, and fructose were used as a source of carbohydrate in a diet, the food intake of rats fed either a Zn-adequate or Zn-deficient diet was evaluated daily over 28 d. The average food intake of all groups of rats fed the Zn-deficient diet was significantly lower than that of the corresponding groups of Zn-adequate control rats. The food intake of the dextrin group was the highest under both Zn-deficient and Zn-adequate diets, and that of the fructose group was the lowest. All rats of the dextrin, maltose, sucrose, glucose, and fructose groups with the Zn-deficient status showed a characteristic cyclic variation in food intake and fitted well to a Cosinor curve. The values of the mesor, amplitude, and period of the food intake cycles showed significant differences among the groups. The higher intake of the glucose diet than the fructose diet of rats fed a Zn-deficient diet may be related to the different metabolisms of the carbohydrates used, from the comparison of the quantities consumed in the corresponding carbohydrates of Zn-adequate diets.

Dihydropyrimidinase deficiency and severe 5-fluorouracil toxicity.

Dihydropyrimidinase (DHP) is the second enzyme in the catabolism of 5-fluorouracil (5FU), and it has been suggested that patients with a deficiency of this enzyme are at risk from developing severe 5FU-associated toxicity. In this study, we demonstrated for the first time that in one patient the severe toxicity, after a treatment with 5FU, was attributable to a partial deficiency of DHP. Analysis of the DHP gene showed that the patient was heterozygous for the missense mutation 833G>A (G278D) in exon 5. Heterologous expression of the mutant enzyme in Escherichia coli showed that the G278D mutation leads to a mutant DHP enzyme without residual activity. An analysis for the presence of this mutation in 96 unrelated Dutch Caucasians indicates that the allele frequency in the normal population is <0.5%. Our results show that a partial DHP deficiency is a novel pharmacogenetic disorder associated with severe 5FU toxicity.

L-threonine supplementation increases the amplitude of the feed intake cycle of rats fed a low-protein zinc-deficient diet.

Rats fed a Zn-deficient diet show characteristic variations in feed intake. These variations were followed by means of a personal computer. The specific feed intake patterns in rats fed a zinc-deficient diet before and after supplementation with protein and several essential amino acids were determined. The high-protein diet decreased the amplitude of feed intake under zinc deficiency, probably because of a decrease in sensitivity to the deficiency. Furthermore, the zinc-deficient diet was supplemented with essential amino acids, and of them L-threonine showed the most marked effect on the increased variability of feed intake.