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

1,12-Dodecanedioic acid, the end-product of omega-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 omega-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.

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Nonenzymatically evoked and cytochrome P450-dependent lipid peroxidation inhibits synthesis of phosphatidylethanolamine via the ethanolamine base exchange reaction in rat liver microsomes

FEBS Letters ◽

10.1016/0014-5793(96)00412-7 ◽

1996 ◽

Vol 386 (1) ◽

pp. 33-38 ◽

Cited By ~ 7

Author(s):

Renata Jasińska ◽

Mariola Rakowska ◽

Jacek Lenart ◽

Izabela Komańska ◽

Sławomir Pikuła

Keyword(s):

Lipid Peroxidation ◽

Cytochrome P450 ◽

Exchange Reaction ◽

Rat Liver ◽

Liver Microsomes ◽

Rat Liver Microsomes ◽

Base Exchange

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Cytochemical analysis of the reconstitution of endoplasmic reticulum after microinjection of rat liver microsomes into Xenopus oocytes.

Journal of Histochemistry & Cytochemistry ◽

10.1177/36.10.2843593 ◽

1988 ◽

Vol 36 (10) ◽

pp. 1263-1273 ◽

Cited By ~ 10

Author(s):

J Paiement ◽

F W Kan ◽

J Lanoix ◽

M Blain

Keyword(s):

Endoplasmic Reticulum ◽

Rat Liver ◽

Smooth Endoplasmic Reticulum ◽

Light And Electron Microscopy ◽

Liver Microsomes ◽

Heat Denaturation ◽

Rat Liver Microsomes ◽

Dependent Manner ◽

Lysosomal Activity

Fragments of rough and smooth endoplasmic reticulum purified from rat liver were injected into Xenopus oocyte cytoplasm. Light and electron microscopy, cytochemistry, immunocytochemistry, and enzyme assay were employed to determine the fate of heterologous membranes in the host cytoplasm. The in vivo-incubated microsomes disappeared in a time-dependent manner. Within 3 hr, rough microsomes were replaced by flattened ER cisternae and smooth microsomes were replaced by a network of anastomosing tubules. Polyclonal antibodies against rat liver microsomes and protein A-gold complexes were applied to glycol methacrylate sections of microinjected oocytes. Specific labeling was observed over discrete rough and smooth ER cisternae 3 hr after microinjection. Endogenous ER was not labeled by this technique, and label was not observed when sections were treated with pre-immune antibodies. Diaminobenzidene cytochemistry of microinjected rat lacrimal gland microsomes revealed enzyme activity in heterologous microsomes after 3 hr of in vivo incubation. Control injected microsomes (inactivated by heat denaturation) became associated with autophagic vacuoles, coincident with changes in lysosomal activity. Freshly isolated un-denatured microsomes did not provoke changes in lysosomal activity, and glucose-6-phosphatase activity associated with microinjected membranes could be detected 21 hr after in vivo incubation. Since rat liver microsomes reconstitute after in vivo incubation into cytoplasmic structures resembling those from which they were derived, we conclude that the microinjected membrane fragments act as templates for their own three-dimensional organization.

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

Acta Biochimica Polonica ◽

10.18388/abp.1998_4294 ◽

1998 ◽

Vol 45 (1) ◽

pp. 119-126 ◽

Cited By ~ 4

Author(s):

J Lenart ◽

I Komańska ◽

R Jasińska ◽

S Pikuła

Keyword(s):

Endoplasmic Reticulum ◽

Body Weight ◽

Cytochrome P450 ◽

Molecular Species ◽

Liver Microsomes ◽

Metabolic Stress ◽

Rat Liver Microsomes ◽

Base Exchange ◽

Single Intraperitoneal Injection ◽

Fold Activation

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 omega-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.

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