Повнотекстовий пошук
Пошуковий запит: (<.>A=Visram M$<.>) |
Загальна кількість знайдених документів : 1
|
1. |
Visram M. The molecular basis of lipid alterations in yeast models of hyperhomocysteinemia [Електронний ресурс] / M. Visram, M. Radulovic, F. H. Hallwirth, S. Steiner, N. Malanovic, H. Wolinski, G. Rechberger, S. D. Kohlwein, O. Tehlivets // Вісник Львівського університету. Серія біологічна. - 2016. - Вип. 73. - С. 247. - Режим доступу: http://nbuv.gov.ua/UJRN/VLNU_biol_2016_73_57 Hyperhomocysteinemia (HHcy) is a common pathological condition that is characterized by high levels of homocysteine (Hcy) in the blood. HHcy is associated with a number of diverse diseases of modern society including cardiovascular and neurological diseases as well as fatty liver and even cancer. The mechanisms underlying the development of Hcy-triggered pathologies are not understood. In HHcy Hcy is converted to S-adenosyl-L-homocysteine (AdoHcy) by Sah1/AHCY and evidence suggests that AdoHcy is indeed a more sensitive marker of HHcy. AdoHcy acts as strong product inhibitor of S-adenosyl-L-methionine (AdoMet)-dependent methyltransfeіrases. Notably, about 50 % of AdoMet in mammals is used for phospholipid methylation. Yeast mutants lacking Sah1 or wild type cells supplemented with Hcy accumulate AdoHcy. These cells also accumulate TG and display an increased fatty acid content and altered composition of their glycerolipids. To discriminate between Hcy and AdoHcy-induced lipid defects we have cloned and expressed an alternative, irreversible bacterial pathway for AdoHcy catabolism. Its expression in sah1 mutants or in wild type cells supplemented with Hcy restores wild-type AdoHcy levels and also fully suppresses alterations in lipid metabolism. AdoHcy accumulation not only impairs phospholipid methylation, but also leads to an up-regulation of fatty acid de novo synthesis at the level of the FAS complex. These data demonstrate that impaired catabolism of AdoHcy affects multiple key steps in lipid metabolism; additional roles for Hcy - independent of its conversion to AdoHcy, for instance in oxidative stress responses - cannot be excluded. Projects P18094 and P24216 supported by FWF.
|
|
|