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Biomedical subjects

W E Donaldson

Publications and source records attributed to W E Donaldson.

At least 73 records · Page 4Linked to original sources
PubMed1977

Selenium inhibition of avian fatty acid synthetase complex.

Injection of 0.48 or 0.72 mg of selenium/100 g body weight (as Na2SeO3) into 3-week-old chicks depressed hepatic activity of fatty acid synthetase compared with saline-injected controls. In in vitro experiments with fatty acid synthetase purified to homogeneity, Na2SeO3 was a competitive inhibitor (Ki = ca. 70 micronM). Dithiothreitol (DTT) at low concentrations increased the inhibition of the enzyme by Na2SeO3. At higher DTT concentrations the potentiating effect of DTT on selenium inhibition of the enzyme disappeared. At still higher DTT concentrations, selenium inhibition of fatty acid synthetase was partically relieved. If DTT and Na2SeO3 (2 : 1 molar ratio, respectively) in inhibitory concentrations, were reacted together prior to addition to enzyme and substrate, no inhibition was observed. Potentiation of selenium inhibition of fatty acid synthetase was observed with 2-mercaptoethanol but not with ascorbate. Several organic seleno-compounds were not inhibitory. The data suggest that selenium inhibits fatty acid synthetase by reversible bonding to the sulfhydryl (SH) groups (possibly at the active sites for acetyl-CoA and/or malonyl-CoA binding) of the enzyme. Selenotrisulfide formation involving selenium and the SH groups from the enzyme and thiol compounds is advanced as a possible explanation for the interaction among Se, DTT and enzyme observed in these experiments.

Animals↗
PubMed1977

Rapid accumulation of cholesterol in serum, liver and aorta of Japanese quail.

Five-week-old, male, Japanese quail (Coturnix coturnix japonica) were given ad lib. access to either a glucose-soybean meal diet with 10% fat and 1% cholesterol (inducer) diet, or a corn-soybean meal (control) diet for 10 weeks. At the beginning of the experiment, and at two week intervals thereafter, quail from each treatment were killed, and the cholesterol concentrations of serum, aorta, and liver, as well as the extent of lipid accumulation in the intima of the aortas were determined. The cholesterol concentration of the serum, aorta, and liver of the control birds remained constant throughout the experiment, while the cholesterol concentration of these organs from birds fed the inducer diet were markedly elevated. At the conclusion of the experiment, the cholesterol concentrations of the serum and liver of birds fed the inducer diet were 6.7 and 14.4 times greater, respectively, than those from the control-fed birds. Approximately 45% of the aortas from the birds fed the inducer diet exhibited moderate to severe (greater than 25% of surface area covered) lipid accumulations at 10 weeks. The rate of cholesterol accumulation appeared to be more rapid than has been reported previously for this species.

Animals↗
PubMed1977

Diet composition and cholesteremia in Japanese quail.

Male, Japanese quail (Coturnix coturnix japonica) were given ad libitum access to one of four diets: a corn-soybean meal control, control plus 1% cholesterol, a glucose-soybean meal with 10% fat plus 1% cholesterol (inducer) or inducer minus 1% cholesterol for an initial 12 weeks beginning at 22 weeks of age. Serum and liver cholesterol concentrations of quail fed the 1% cholesterol supplemented diets averaged respectively, 5.3 and 10.3 times higher than those from quail fed the corresponding diets without cholesterol. There were no significant differences in serum and liver cholesterol concentrations between groups of quail fed control diet versus inducer minus 1% cholesterol diet or between quail fed inducer diet versus control plus 1% cholesterol diet. During a second 12-week period, the quail previously fed the diets containing cholesterol were given the respective control diets. The serum and liver cholesterol concentrations returned to values comparable to those of quail fed the corresponding diets without cholesterol throughout the experiment.

Animals↗
PubMed1976

The effects of mercury ingestion on hepatic mitochondrial membranes of chicks.

Cytochrome c oxidase activity was measured in livers of chicks receiving 0, 200,250 or 300 p.p.m. mercury (as HgC12) in the drinking water beginning at one week of age. In the first experiment treatment with 200 p.p.m. mercury for up to 4 weeks tended to increase the activity of cytochrome c oxidase and decrease the proportion of free (measured in untreated liver preparations) to total (measured in Triton X-100 treated liver preparations) enzyme activity as compared with controls. However, the differences, which appeared after 1 week of treatment were not always statistically significant. The fatty acid composition of mitochondrial lipids was not affected by treatment with 200 p.p.m. mercury for 4 weeks. In the second experiment, treatment with 300 p.p.m. mercury for 4 weeks resulted in significantly higher total cytochrome c oxidase specific activity and a significantly lower proportion of free to total enzyme activity as compared with controls. However, mitochondrial susceptibility to rupture by freezing and thawing was not affected. In the third experiment chicks were given 250 p.p.m. mercury in the drinking water from 1 through 9 weeks of age. The mercury-treated chicks exhibited severe tremors at 9 weeks while the controls were unaffected. Cytochome c oxidase total specific activity was significantly reduced in trembling chicks, and the proportion of free to total enzyme activity was significantly increased as was the susceptibility of isolated mitochondria to rupture by freezing and thawing. The data suggest that moderate levels of mercury administered over an 8 week period can affect adversely the integrity of mitochondrial membranes.

Animals↗
PubMed1975

Mercury inhibition of avian fatty acid synthetase complex.

(1) Subcutaneous or intra-abdominal injections of 8 mg of HgCl2/100 g body weight markedly depressed hepatic fatty acid synthetase activity of chicks at 1 h post-injection. The depression occurred despite the fact that the chicks continued to eat up until the time they were killed. Under these same conditions, the hepatic activity of acetyl-CoA carboxylase (EC 6.4.1.2) was not affected by HgCl2, while the activity of the mitochondrial system of fatty acid elongation was stimulated. (2) When 2-mercaptoethanol was included in the incubation medium for a highly purified preparation of fatty acid synthetase, 500 muM HgCl2 was required to show definite inhibition of the enzyme. When 2-mercaptoethanol was omitted, 50 muM HgCl2 was inhibitory and 100 muM HgCl2 abolished enzyme activity. (3) 2 mM dithiothreitol completely protected the purified fatty acid synthetase preparation from inhibition by 100 muM HgCl2. When dithiothreitol was added after the addition of enzyme to the mercury-containing medium, protection of the enzyme was not complete. (4) Dialysis of cytosol fractions from chicks injected with HgCl2 against 500 vol. of 0.2 M potassium phosphate buffer (pH 7.0) containing 1 mM EDTA and 10 mM dithiothreitol for 4 h at 4 degrees stimulated the fatty acid synthetase activity of the fractions. Dialysis of cytosol fractions from noninjected chicks under the same conditions was without effect on fatty acid synthetase activity. (5) These data support the hypothesis that the inhibitory effect of HgCl2 administered in vivo on hepatic fatty acid synthetase activity in chicks is mediated through the interaction of mercury with the sulfhydryl groups of the enzyme.

Acetyl-CoA Carboxylase↗
PubMed1975

Mercury inhibition of fatty acid synthesis in chicks.

Male chicks were fed a commercial ration and were given drinking water which contained 0, 50, 100, 150, 200 or 300 mug of mercury/ml as mercuric chloride from hatching to 3 weeks of age. In one experiment, the mercuric chloride was administered by injection into the abdominal cavity rather than in the drinking water. At 3 weeks the chicks were killed, and the livers were removed and weighed. The activity of fatty acid synthetase in the 800 X gav supernatant fractions of the liver homogenates and in vivo incorporation of [14C]acetate into liver and carcass fatty acids and respiratory 14CO2 was determined as indicated. Administration of mercury at a treatment level of 300 mug/ml of drinking water depressed growth, feed and water consumption, liver weight, hepatic fatty acid synthetase activity, and in vivo incorporation of [14C]acetate into liver and carcass fatty acids, and increased the production of respiratory 14CO2 as compared with controls. In experiments in which graded doses of mercury were administered, body weights, liver weights, and feed and water intakes of the chicks receiving 0, 50 and 100 mug of mercury/ml of drinking water were similar to each other, but these parameters were severely depressed by 200 mug of mercury/ml of drinking water. Mercury caused a dose-related decrease of fatty acid synthetase activity. Incorporation of [14C]acetate into carcass fatty acid was depressed by 50 and 200 mug of mercury/ml of drinking water; incorporation into liver fatty acids and production of respiratory 14CO2 was not affected by mercury. Intra-abdominal injection of 6 mg of mercury/100 g body weight (as mercuric chloride) into well alimented chicks depressed hepatic fatty acid synthetase activity at 1 h post-injection. The data are consistent with the hypothesis that a portion of the effects of mercury on fatty acid synthesis are direct rather than a secondary effect of inanition.

Acetates↗
PubMed1975

Mercuric chloride effects on the activities of some hepatic enzymes in chicks.

Three groups of 6 male chicks each were fed a commercial diet and were given drinking water which contained either 0, 150 or 300 mug. of mercury/ml. as mercuric chloride from hatching to 3 weeks of age. The chicks were killed, the livers were removed and weighed, and the activities of selected enzymes were measured in the 800 X gav supernatant fractions of the liver homogenates. Liver weights were depressed from control values in chicks receiving 300 p.p.m. mercury but not in chicks receiving 150 p.p.m. Fatty acid synthetase specific activity was depressed by both levels of added mercury, but microsomal fatty acid elongation was depressed only by 300 p.p.m. of mercury. Both levels of added mercury stimulated acid phosphatase specific activity. The speecific activities of cytochrome c oxidase, glucose-6-phosphatase and 6-phosphogluconate dehydrogenase were unaffected by added mercury. The data support the hypothesis that mercury administration does not result in generalized hepatotoxicity.

Acid Phosphatase↗