TY - JOUR
T1 - Human very-long-chain Acyl-CoA synthetase
T2 - Cloning, topography, and relevance to branched-chain fatty acid metabolism
AU - Steinberg, Steven J.
AU - Wang, Susan J.
AU - Kim, Do G.
AU - Mihalik, Stephanie J.
AU - Watkins, Paul A.
N1 - Funding Information:
We thank Drs. Catherine Thompson (COS-1 cells), Gordon Tomas-celli (human heart RNA), Joel Avigan (methyl pristanate), He-Ming Wei (glyceraldehyde-3-phosphate dehydrogenase oligonucleotide primers), and Kirby D. Smith and Hugo W. Moser for many thoughtful discussions. This work was supported by NIH Grants NS10533, HD10981, and DK51149.
PY - 1999/4/13
Y1 - 1999/4/13
N2 - Very-long-chain acyl-CoA synthetases (VLCS) activate very-long-chain fatty acids (VLCFA) containing 22 or more carbons to their CoA derivatives. We cloned the human ortholog (hVLCS) of the gene encoding the rat liver enzyme (rVLCS). Both hVLCS and rVLCS contain 620 amino acids, are expressed primarily in liver and kidney, and have a potential peroxisome targeting signal 1 (-LKL) at their carboxy termini. When expressed in COS-1 cells, hVLCS activated the VLCFA lignoceric acid (C24:0), a long-chain fatty acid (C16:0), and two branched-chain fatty acids, phytanic acid and pristanic acid. Immunofluorescence and immunoblot studies localized hVLCS to both peroxisomes and endoplasmic reticulum. In peroxisomes of HepG2 cells, hVLCS was topographically oriented facing the matrix and not the cytoplasm. This orientation, coupled with the observation that hVLCS activates branched-chain fatty acids, suggests that hVLCS could play a role in the intraperoxisomal reactivation of pristanic acid produced via α-oxidation of phytanic acid.
AB - Very-long-chain acyl-CoA synthetases (VLCS) activate very-long-chain fatty acids (VLCFA) containing 22 or more carbons to their CoA derivatives. We cloned the human ortholog (hVLCS) of the gene encoding the rat liver enzyme (rVLCS). Both hVLCS and rVLCS contain 620 amino acids, are expressed primarily in liver and kidney, and have a potential peroxisome targeting signal 1 (-LKL) at their carboxy termini. When expressed in COS-1 cells, hVLCS activated the VLCFA lignoceric acid (C24:0), a long-chain fatty acid (C16:0), and two branched-chain fatty acids, phytanic acid and pristanic acid. Immunofluorescence and immunoblot studies localized hVLCS to both peroxisomes and endoplasmic reticulum. In peroxisomes of HepG2 cells, hVLCS was topographically oriented facing the matrix and not the cytoplasm. This orientation, coupled with the observation that hVLCS activates branched-chain fatty acids, suggests that hVLCS could play a role in the intraperoxisomal reactivation of pristanic acid produced via α-oxidation of phytanic acid.
UR - http://www.scopus.com/inward/record.url?scp=0033551122&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033551122&partnerID=8YFLogxK
U2 - 10.1006/bbrc.1999.0510
DO - 10.1006/bbrc.1999.0510
M3 - Article
C2 - 10198260
AN - SCOPUS:0033551122
SN - 0006-291X
VL - 257
SP - 615
EP - 621
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -