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Biomedical subjects

A T Diplock

Publications and source records attributed to A T Diplock.

At least 73 records · Page 4Linked to original sources

Glutathione peroxidase (EC 1.11.1.9), glutathione-S-transferase (EC 2.5.1.13), superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6) activities in tissues of ducklings deprived of vitamin E and selenium.

Vitamin E and selenium deficiencies were produced in the Pekin duckling (Anser cinerens) and were characterized by the development of lesions after 14 d in gizzard, intestine, heart and skeletal muscle. The activities of glutathione peroxidase (EC 1.11.1.9), using hydrogen peroxide and cumene hydroperoxide as substrates, glutathione-S-transferase (EC 2.5.1.13), superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6) were measured in homogenate supernatant fractions of liver, heart, intestine, gizzard and skeletal muscle of deficient ducklings and of control birds given vitamin E or Se or both. Glutathione peroxidase activities were dramatically lower in tissues of Se-deficient ducklings, and this was unaffected by vitamin E. No adaptive changes were seen in the activity of the other enzymes, even after 21 d when the deficiency was severe. It appeared likely that the variability of the enzyme activities, other than glutathione peroxidase, in the different tissues studied might explain differences among the tissues in susceptibility to peroxidative damage.

Animals↗

The modulating influence of vitamin E in biological membrane unsaturated phospholipid metabolism.

A tissue culture system in which the composition of the medium, with respect to vitamin E, linoleic acid, and cholesterol, can be manipulated at will, was used to study the effect of vitamin E on the fatty acid profiles of fibroblast membrane phospholipids. The effect was studied of alpha-tocopherol, and of butylated hydroxytoluene, on the uptake of isotopically labeled linoleic acid and cholesterol, and of the effect of these antioxidants on the metabolic interconversion of linoleic acid with other unsaturated fatty acids. Butylated hydroxytoluene was without effect on any of the parameters measured, alpha-tocopherol caused a large enhancement in the content and radioactivity of the arachidonyl residues of phosphatidyl choline, phosphatidyl serine, and phosphatidyl ethanolamine, generally at the expense of linoleic acid in the same phospholipids. There was no effect of alpha-tocopherol on the unsaturated fatty acids of the neutral lipids, suggesting that there was no general effect on the chain elongation and desaturation of linoleic acid. The results are thought to demonstrate a specific effect of alpha-tocopherol upon the architecture of membrane phospholipids by controlling the profiles of their unsaturated fatty acid components. The uptake of radioactive cholesterol, and the content of cholesterol and cholesterylesters in cultured cells was also significantly increased by the presence of alpha-tocopherol in the medium.

Animals↗

Metabolic and functional defects in selenium deficiency.

This paper is concerned with present-day knowledge of the biological role of selenium, of its interaction with other nutrients including trace elements, and with the importance of selenium in human nutrition and health. Selenium has been shown to be an integral part of glutathione peroxidase, which catalyses the reduction of a large range of lipid hydroperoxides and hydrogen peroxide. The interrelation between vitamin E, selenium and polyunsaturated fatty acids is complex. First, selenium in glutathione peroxidase may control intracellular levels of hydrogen peroxide, which affect the formation of active oxygen metabolites that may serve as initiators of lipid peroxidation; this role of selenium is closely related to that of superoxide dismutases, which control intracellular levels of the superoxide anion. Secondly, vitamin E may control the formation of lipid hydroperoxides through its antioxidant function, as well as possibly entering into a structural relation with membrane phospholipids. Thirdly, glutathione peroxidase may catalyse the reduction of lipid hydroperoxides, formed from membrane lipids, to hydroxyacids without detriment to the cellular economy. In the field of human nutrition, the lack of selenium has been shown to be the cause of a cardiomyopathy known as Keshan disease, occurring in the People's Republic of China. Blood selenium levels in patients from this area are compared with blood selenium levels in three other parts of the world and the conclusion is reached that the blood selenium level of populations in Keshan disease regions are exceptionally low and that Keshan disease is the first demonstration that selenium is an essential trace element for man.

Animal Nutritional Physiological Phenomena↗

Interactions of tocopherols and ubiquinones with monolayers of phospholipids.

1. The penetration of alpha-tocopherol and seven of its derivatives, and five compounds in the ubiquinone series, having differing chain lengths, into monolayers at the air/water interface of 11 different synthetic phospholipids and cholesterol was investigated; the properties of mixed monolayers of the tocopherols and of ubiquinones with phospholipids were also studied. 2. Penetration of alpha-tocopherol into diarachidonylglycerylphosphorycholine was approximately constant for molar ratios of tocopherol/phospholipid ranging from 0.4:1.0 to 2.0:1.0. 3. Tocopherols with shorter or longer side chains than alpha-tocopherol had a lesser ability to penetrate monolayers of phospholipid molecules with 16 or more carbon atoms in their acyl chains. 4. All the tocopherols penetrated more readily as unsaturation in the phospholipids was increased, and their penetration into mixed monolayers of phospholipids was greatly facilitated by the presence of relatively small quantities of unsaturated phospholipid molecules. 5. There was relatively little interaction between the tocopherols and cholesterol, or between the ubiquinones and phospholipids. 6. The possible significance of the observed interactions between alpha-tocopherol and polyunsaturated phospholipids is discussed in relation to the biochemical actions of alpha-tocopherol in vivo. 7. It is suggested that fluidity of the lipid bilayer in membranes containing polyunsaturated phospholipids may allow alpha-tocopherol to interact in a dynamic manner with a number of phospholipid molecules.

Membranes↗

The dependence on vitamin E and selenium of drug demethylation in rat liver microsomal fractions.

1. The effects of vitamin E deficiency, and of vitamin E and selenium deficiency, on rat liver microsomal aminopyrine demethylase activity were investigated. It was found that, over a wide range of substrate concentrations, the enzyme activity in preparations from deficient animals was significantly lower than that in controls. 2. Addition of antioxidants in vitro, either to the homogenization or to the assay media, was without significant effect on the depressed enzyme activity. Castration and alteration in dietary protein concentration were also without effect. The rate of oxidation of NADPH was however, lower in preparations from deficient animals. 3. Lineweaver-Burk plots of the reciprocal of enzyme activity and substrate concentration showed a higher Km value in preparations from vitamin E-deficient animals, irrespective of whether selenium was present; the Vmax. was unaffected. These parameters were unchanged when antioxidants were added in vitro. Induction with phenobarbitone and 3-methylcholanthrene showed large changes in Km value which, for preparations from vitamin E-deficient animals, was higher than that for corresponding controls. 4. Examination of the synergism between NADH and NADPH as donors of reducing equivalents for aminopyrine demethylation showed that vitamin E and selenium were only minimally involved in the phenomenon. However, both the initial rate and the extent of demethylation were significantly lower in vitamin E- and selenium-deficient preparations and both nutrients were required for the restoration of full activity. 5. The significance of these results is discussed in the light of our working hypothesis.

Aminopyrine↗

The nature of the acid-volatile selenium in the liver of the male rat.

1. The properties of rat liver acid-volatile selenium have been compared with those of H(2)Se and (CH(3))(2)Se. 2. In model experiments oxidation-sensitive H(2) (75)Se was trapped quantitatively under anaerobic conditions in 0.1m-AgNO(3), and (CH(3))(2) (75)Se was trapped quantitatively in 8m-HNO(3). The acid-labile selenium of a liver homogenate, and of a microsomal fraction, was found to behave quite unlike (CH(3))(2) (75)Se and in a manner indistinguishable from H(2) (75)Se. 3. It was concluded that the acid-volatile material is certainly not (CH(3))(2)Se and that it is probably H(2)Se. 4. The significance of these findings is discussed in relation to current knowledge about the metabolism and detoxication of selenium, and a scheme is proposed which incorporates this knowledge with recent observations on the interactions between trace amounts of selenium and tocopherol, and the production of acute selenium deficiency by Ag(+) in vitamin E-deficient rats.

Animals↗