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1

10-undecynoic acid, an inhibitor of cytochrome P450 4A1, inhibits ethanolamine-specific phospholipid base exchange reaction in rat liver microsomes

100%
Lenart J., Pikula S.
Acta Biochimica Polonica
|
1999
|
tom 46
|
nr 1
1,12-Dodecanedioic acid, the end-product of w-hydroxylation of lauric acid, stimulates in a concentration dependent manner, phosphatidylethanolamine synthesis via ethanolamine-specific phospholipid base exchange reaction in rat liver endoplasmic reticulum. On the other hand, administration to rats of 10-undecynoic acid, a specific inhibitor of w-hydroxylation reaction catalyzed by cytochrome P450 4A1, inhibits the ethanolamine-specific phospholipid base exchange activity by 30%. This is accompanied by a small but significant decrease in phosphatidylethanolamine content in the endoplasmic reticulum and inhibition of cytochrome P450 4A1. On the basis of these results it can be proposed that a functional relationship between cytochrome P450 4A1 and phosphatidylethanolamine synthesis exists in rat liver. Cytochrome P450 4A1 modulates the cellular level of lauric acid, an inhibitor of phospholipid synthesis. In turn, ethanolamine-specific phospholipid base exchange reaction provides molecular species of phospholipids, containing mainly long-chain polyunsaturated fatty acid moieties, required for the optimal activity of cytochrome P450 4A1.
2

Methylation demand: a key determinant of homocysteine metabolism

84%
Brosnan J. T., Jacobs R. L., Stead L. M., Brosnan M. E.
Acta Biochimica Polonica
|
2004
|
tom 51
|
nr 2
Elevated plasma homocysteine is a risk factor for cardiovascular disease and Alz­heimer's disease. To understand the factors that determine the plasma homocysteine level it is necessary to appreciate the processes that produce homocysteine and those that remove it. Homocysteine is produced as a result of methylation reactions. Of the many methyltransferases, two are, normally, of the greatest quantitative impor­tance. These are guanidinoacetate methyltransferase (that produces creatine) and phosphatidylethanolamine ^-methyltransferase (that produces phosphatidylcholine). In addition, methylation of DOPA in patients with Parkinson's disease leads to increased homocysteine production. Homocysteine is removed either by its irreversible conversion to cysteine (transsulfuration) or by remethylation to methionine. There are two separate remethylation reactions, catalyzed by betaine:homocysteine methyltransferase and methionine synthase, respectively. The reactions that remove homocysteine are very sensitive to B vitamin status as both the transsulfuration enzymes contain pyridoxal phosphate, while methionine synthase contains cobalamin and receives its methyl group from the folic acid one-carbon pool. There are also important genetic influences on homocysteine metabolism.
3

The induction of cytochrome P450 isoform, CYP4A1, by clofibrate coincides with activation of ethanolamine-specific phospholipid base exchange reaction in rat liver microsomes

84%
Lenart J., Komanska I., Jasinska R., Pikula S.
Acta Biochimica Polonica
|
1998
|
tom 45
|
nr 1
Administration of a hypolipidaemic drug, clofibrate, to rats resulted, 24 h after a single intraperitoneal injection (250 mg/kg body weight), in pronounced enhancement of the rate of phosphatidylethanolamine (PE) synthesis via the PE-specific base exchange (PEBE) reaction in liver microsomes. This was accompanied by 3.4-fold activation of microsomal ω-hydroxylation of lauric acid by cytochrome P450 4A1 isoform (CYP4A1) and an increase in the protein content of this isoform in endoplasmic reticulum (ER) membranes. Since PE represents a class of phospholipids (PL) prerequisite for proper functioning of CYP4A1, and the PEBE reaction is an inducible pathway of PL synthesis in hepatocytes under metabolic stress, one may speculate that this reaction is switched on when extensive remodelling of PL molecular species or/and massive synthesis of lipid bilayer components for membrane assembly is required.
4

Synthesis of aminophospholipids in Saccharomyces cerevisiae and Chinese hamster ovary cells. From mutagenesis to genes and cellular function

59%
Lenart J., Pikula S.
Cellular and Molecular Biology Letters
|
1998
|
tom 03
|
nr 2
The purpose of this article is to provide a concise overview of the characterization of auxotrophic mutated cells to the precursors of lipid synthesis, and of the identification of specific genes encoding enzymatic proteins involved in this process. The focus is on enzymes catalyzing the synthesis of phosphatidylserine and phosphatidylethanolamine in Saccharomyces cerevisiae and Chinese hamster ovary cells, two cell types frequently used by investigators studying the mechanisms of genetic control of metabolic processes.
5

Synthesis of aminophospholipids in Saccharomyces cerevisiae and Chinese hamster ovary cells. From mutagenesis to genes and cellular function

51%
Lenart J., Pikula S.
Cellular and Molecular Biology Letters
|
1998
|
tom 03
|
nr 3
The purpose of this article is to provide a concise overview of the characterization of auxotrophic mutated cells to the precursors of lipid synthesis, and of the identification of specific genes encoding enzymatic proteins involved in this process. The focus is on enzymes catalyzing the synthesis of phosphatidylserine and phosphatidylethanolamine in Saccharomyces cerevisiae and Chinese hamster ovary cells, two cell types frequently used by investigators studying the mechanisms of genetic control of metabolic processes.
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