Identification of a Mammalian Long Chain Fatty Acyl Elongase Regulated by Sterol Regulatory Element-binding Proteins

Young Ah Moon, Nila A. Shah, Suchismita Mohapatra, Janet A. Warrington, Jay D. Horton

Research output: Contribution to journalArticle

231 Citations (Scopus)

Abstract

Fatty acids are synthesized de novo from acetyl-CoA and malonyl-CoA through a series of reactions mediated by acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). In rodents, the principal fatty acid produced by FAS is palmitic acid (16:0). Sterol regulatory element-binding proteins (SREBPs) enhance the transcription of many genes responsible for fatty acid synthesis. In transgenic mice that overexpress SREBPs in liver, the rate of fatty acid synthesis is markedly increased, owing to the activation of these biosynthetic genes, which include ATP citrate lyase, ACC, FAS, and stearoyl-CoA desaturase. The fatty acids that accumulate in livers of SREBP transgenic mice are 18 carbons rather than 16 carbons in length, suggesting that the enzymes required for the elongation of palmitic to stearic acid may be induced. Here, we report the cDNA cloning of a murine long chain fatty acyl elongase (LCE) that was identified initially by oligonucleotide array analysis of mRNA from SREBP transgenic mouse livers. LCE mRNA is highly expressed in liver and adipose tissue. The cDNA encodes a protein of 267 amino acids that shares sequence identity with previously identified very long chain fatty acid elongases. Cells that overexpress LCE show enhanced addition of 2-carbon units to C12-C16 fatty acids. We provide evidence that LCE catalyzes the rate-limiting condensing step in this reaction. The current studies suggest that mouse LCE expression is increased by SREBPs and that the enzyme is a component of the elusive mammalian elongation system that converts palmitic to stearic acid.

Original languageEnglish (US)
Pages (from-to)45358-45366
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number48
DOIs
StatePublished - Nov 30 2001

Fingerprint

Sterol Regulatory Element Binding Proteins
Fatty Acids
Fatty Acid Synthases
Liver
Transgenic Mice
Acetyl-CoA Carboxylase
Carbon
Elongation
Complementary DNA
Genes
ATP Citrate (pro-S)-Lyase
Stearoyl-CoA Desaturase
Malonyl Coenzyme A
Messenger RNA
Acetyl Coenzyme A
Palmitic Acid
Cloning
Enzymes
Transcription
Oligonucleotide Array Sequence Analysis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Identification of a Mammalian Long Chain Fatty Acyl Elongase Regulated by Sterol Regulatory Element-binding Proteins. / Moon, Young Ah; Shah, Nila A.; Mohapatra, Suchismita; Warrington, Janet A.; Horton, Jay D.

In: Journal of Biological Chemistry, Vol. 276, No. 48, 30.11.2001, p. 45358-45366.

Research output: Contribution to journalArticle

Moon, Young Ah ; Shah, Nila A. ; Mohapatra, Suchismita ; Warrington, Janet A. ; Horton, Jay D. / Identification of a Mammalian Long Chain Fatty Acyl Elongase Regulated by Sterol Regulatory Element-binding Proteins. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 48. pp. 45358-45366.
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