Mutation for Nonsyndromic Mental Retardation in the trans-2-Enoyl-CoA Reductase TER Gene Involved in Fatty Acid Elongation Impairs the Enzyme Activity and Stability, Leading to Change in Sphingolipid Profile

Abe, Kensuke; Ohno, Yusuke; Sassa, Takayuki; Taguchi, Ryo; Çalışkan, Minal; Ober, Carole; Kihara, Akio

doi:10.1074/jbc.m113.493221

Cited by 31 publications

(27 citation statements)

References 31 publications

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“…Implicitly, this indicates that ELOVL1‐7 interact with the other enzymes, KAR, TER, and HACD1‐4, in the fatty acid chain elongation system to form the elongase complex . Among the elongase complex, KAR, which catalyzes the first reduction step in elongation system (reducing 3‐ketoacyl‐CoA to 3‐hydroxyacyl‐CoA) following the ELOVL1‐7‐mediated condensation step in mammals , could enhance ELOVL6 activity in both KAR‐dependent and KAR‐independent manner ; KER, catalyzing the second reduction step following HACD1‐4‐mediated dehydration, may indirectly affect HACD1‐4 performance as well . Since ELOVL1‐7 catalyze the first and rate‐limiting step in elongation system, and are overexpressed to a similar extent in this study, we only take ELOVL1‐7, but not the whole elongase complex into consideration.…”

Section: Discussionmentioning

confidence: 99%

Identification of genes mediating branched chain fatty acid elongation

Wang

Park

et al. 2019

FEBS Letters

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Saturated branched chain fatty acids (BCFA) terminating with either a prop‐2‐yl (iso) or sec‐butan‐2‐yl (anteiso) group are common bioactive food components consumed from beef, fish, and dairy products. Little is known about the endogenous metabolism of BCFA and the enzymes mediating their interconversions. By using transient transfection studies, we report for the first time the substrate specificity of the elongase of very long chain fatty acids (ELOVL)1‐7 toward anteiso‐15:0 and iso‐18:0, and assessed competition between BCFA and normal saturated fatty acids (n‐SFA). ELOVL6 mediates elongation of anteiso‐15:0→anteiso‐17:0, while ELOVL3 is active toward iso‐18:0→iso‐20:0. Competition studies reveal n‐16:0 competes with anteiso‐15:0 for ELOVL6, while n‐18:0 competes with iso‐18:0 for ELOVL3. These competitions for elongation may have implications in specialized tissues where both BCFA and n‐SFA are present at comparable levels.

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Section: Discussionmentioning

confidence: 99%

Identification of genes mediating branched chain fatty acid elongation

Wang

Park

et al. 2019

FEBS Letters

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“…CerS expression does not always correspond to SL chain length profiles, possibly a result of post-translational modifications (Laviad et al, 2008(Laviad et al, , 2012 or substrate availability (Abe et al, 2013). Recently, homo-or heterodimer CerS formation was demonstrated experimentally and the dimerization roles played by CerS are being investigated (Mesicek et al, 2010;Laviad et al, 2012).…”

Section: Cers Regulationmentioning

confidence: 99%

The effect of altered sphingolipid acyl chain length on various disease models

Park

2015

Biological Chemistry

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Sphingolipids have emerged as an important lipid mediator in intracellular signalling and metabolism. Ceramide, which is central to sphingolipid metabolism, is generated either via a de novo pathway, by attaching fatty acyl CoA to a long-chain base, or via a salvage pathway, by degrading pre-existing sphingolipids. As a 'sphingolipid rheostat' has been proposed, the balance between ceramide and sphingosine-1-phosphate has been the object of considerable attention. Ceramide has recently been reported to have a different function depending on its acyl chain length: six ceramide synthases (CerS) determine the specific ceramide acyl chain length in mammals. All CerS-deficient mice generated to date show that sphingolipids with defined acyl chain lengths play distinct pathophysiological roles in disease models. This review describes recent advances in understanding the associations of CerS with various diseases and includes clinical case reports.

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“…As far as the third isoform of testosterone α-reductase (SRD5A3, also known as polyprenol reductase), available data report recovery from the microsomal fraction [8] and transient expression in HeLa cells yielded cytoplasmic localization, and no detectable activity [36] . For the TECR enzyme, immunohistochemistry has clearly suggested a localization in the ER [12] . No data is available for the TECRL that has been described only at the gene level.…”

Section: Discussionmentioning

confidence: 99%

“…Trans-2-Enoyl-CoA reductase (TER or TECR) comes as a more recent addition to the SRD5A family. This gene, when mutated, causes a rare autosomic syndrome, nonsyndromic mental retardation, and the protein carries out the fourth step of very long-chain fatty acid synthesis and sphingosine degradation [12] . TECR expression seems ubiquitous in man and mouse organs by Northern blot analysis [13] , with high expression in the nervous system [14] consistently with its involvement in the synthesis of membrane lipids and with congenital neurological impairment arising from mutations.…”

Section: Introductionmentioning

confidence: 99%

Subcellular localization of the five members of the human steroid 5α-reductase family

et al. 2017

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In humans the steroid 5α-reductase (SRD5A) family comprises five integral membrane enzymes that carry out reduction of a double bond in lipidic substrates: Δ4-3-keto steroids, polyprenol and trans-enoyl CoA. The best-characterized reaction is the conversion of testosterone into the more potent dihydrotestosterone carried out by SRD5A1-2. Some controversy exists on their possible nuclear or endoplasmic reticulum localization.We report the cloning and transient expression in HeLa cells of the five members of the human steroid 5α-reductase family as both N- and C-terminus green fluorescent protein tagged protein constructs. Following the intrinsic fluorescence of the tag, we have determined that the subcellular localization of these enzymes is in the endoplasmic reticulum, upon expression in HeLa cells. The presence of the tag at either end of the polypeptide chain can affect protein expression and, in the case of trans enoyl-CoA reductase, it induces the formation of protein aggregates.

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Mutation for Nonsyndromic Mental Retardation in the trans-2-Enoyl-CoA Reductase TER Gene Involved in Fatty Acid Elongation Impairs the Enzyme Activity and Stability, Leading to Change in Sphingolipid Profile

Cited by 31 publications

References 31 publications

Identification of genes mediating branched chain fatty acid elongation

Identification of genes mediating branched chain fatty acid elongation

The effect of altered sphingolipid acyl chain length on various disease models

Subcellular localization of the five members of the human steroid 5α-reductase family

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