Stearoyl-CoA desaturase 1 deficiency increases CTP: choline cytidylyltransferase translocation into the membrane and enhances phosphatidylcholine synthesis in liver

Agnieszka Dobrzyn, Pawel Dobrzyn, Makoto Miyazaki, Harini Sampath, Kiki Chu, James M. Ntambi

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme in monounsaturated fatty acid synthesis. Previously, we showed that Scd1 deficiency reduces liver triglyceride accumulation and considerably decreases synthesis of very low density lipoprotein and its secretion in both lean and obese mice. In the present study, we found that Scd1 deficiency significantly modulates hepatic glycerophospholipid profile. The content of phosphatidylcholine (PC) was increased by 40% and the activities of CTP:choline cytidylyltransferase (CCT), the rate-limiting enzyme in de novo PC synthesis, and choline phosphotransferase were increased by 64 and 53%, respectively, in liver of Scd1-/- mice. In contrast, the protein level of phosphatidylethanolamine N-methyltransferase, an enzyme involved in PC synthesis via methylation of phosphatidylethanolamine, was decreased by 80% in the liver of Scd1-/- mice. Membrane translocation of CCT is required for its activation. Immunoblot analyses demonstrated that twice as much CCTa was associated with plasma membrane in livers of Scd1-/- compared with wild type mice, suggesting that Scd1 mutation leads to an increase in CCT membrane affinity. The incorporation of [3H]glycerol into PC was increased by 2.5-fold in Scd1-/- primary hepatocytes compared with those of wild type mice. Furthermore, mitochondrial glycerol-3-phosphate acyltransferase activity was reduced by 42% in liver of Scd1-/- mice; however, the activities of microsomal glycerol-3-phosphate acyltransferase, diacylglycerol acyltransferase, and ethanolamine phosphotransferase were not affected by Scd1 mutation. Our study revealed that SCD1 deficiency specifically increases CCT activity by promoting its translocation into membrane and enhances PC biosynthesis in liver.

Original languageEnglish (US)
Pages (from-to)23356-23362
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number24
DOIs
StatePublished - Jun 17 2005
Externally publishedYes

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Stearoyl-CoA Desaturase
Cytidine Triphosphate
Choline
Phosphatidylcholines
Liver
Membranes
Acyltransferases
Phosphatidylethanolamine N-Methyltransferase
Phosphotransferases
Enzymes
Diacylglycerol O-Acyltransferase
Glycerophospholipids
Monounsaturated Fatty Acids
Ethanolamine
Methylation
VLDL Lipoproteins
Biosynthesis
Obese Mice
Mutation
Cell membranes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Stearoyl-CoA desaturase 1 deficiency increases CTP : choline cytidylyltransferase translocation into the membrane and enhances phosphatidylcholine synthesis in liver. / Dobrzyn, Agnieszka; Dobrzyn, Pawel; Miyazaki, Makoto; Sampath, Harini; Chu, Kiki; Ntambi, James M.

In: Journal of Biological Chemistry, Vol. 280, No. 24, 17.06.2005, p. 23356-23362.

Research output: Contribution to journalArticle

Dobrzyn, Agnieszka ; Dobrzyn, Pawel ; Miyazaki, Makoto ; Sampath, Harini ; Chu, Kiki ; Ntambi, James M. / Stearoyl-CoA desaturase 1 deficiency increases CTP : choline cytidylyltransferase translocation into the membrane and enhances phosphatidylcholine synthesis in liver. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 24. pp. 23356-23362.
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T2 - choline cytidylyltransferase translocation into the membrane and enhances phosphatidylcholine synthesis in liver

AU - Dobrzyn, Agnieszka

AU - Dobrzyn, Pawel

AU - Miyazaki, Makoto

AU - Sampath, Harini

AU - Chu, Kiki

AU - Ntambi, James M.

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AB - Stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme in monounsaturated fatty acid synthesis. Previously, we showed that Scd1 deficiency reduces liver triglyceride accumulation and considerably decreases synthesis of very low density lipoprotein and its secretion in both lean and obese mice. In the present study, we found that Scd1 deficiency significantly modulates hepatic glycerophospholipid profile. The content of phosphatidylcholine (PC) was increased by 40% and the activities of CTP:choline cytidylyltransferase (CCT), the rate-limiting enzyme in de novo PC synthesis, and choline phosphotransferase were increased by 64 and 53%, respectively, in liver of Scd1-/- mice. In contrast, the protein level of phosphatidylethanolamine N-methyltransferase, an enzyme involved in PC synthesis via methylation of phosphatidylethanolamine, was decreased by 80% in the liver of Scd1-/- mice. Membrane translocation of CCT is required for its activation. Immunoblot analyses demonstrated that twice as much CCTa was associated with plasma membrane in livers of Scd1-/- compared with wild type mice, suggesting that Scd1 mutation leads to an increase in CCT membrane affinity. The incorporation of [3H]glycerol into PC was increased by 2.5-fold in Scd1-/- primary hepatocytes compared with those of wild type mice. Furthermore, mitochondrial glycerol-3-phosphate acyltransferase activity was reduced by 42% in liver of Scd1-/- mice; however, the activities of microsomal glycerol-3-phosphate acyltransferase, diacylglycerol acyltransferase, and ethanolamine phosphotransferase were not affected by Scd1 mutation. Our study revealed that SCD1 deficiency specifically increases CCT activity by promoting its translocation into membrane and enhances PC biosynthesis in liver.

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