PMID- 10479480
OWN - NLM
STAT- MEDLINE
DCOM- 19991019
LR  - 20071114
IS  - 1096-7192 (Print)
IS  - 1096-7192 (Linking)
VI  - 68
IP  - 1
DP  - 1999 Sep
TI  - Human liver-specific very-long-chain acyl-coenzyme A synthetase: cDNA cloning and
      characterization of a second enzymatically active protein.
PG  - 32-42
AB  - Activation of fatty acids, catalyzed by acyl-coenzyme A (acyl-CoA) synthetases,
      is required for their subsequent metabolism. Peroxisomes and microsomes contain
      very-long-chain acyl-CoA synthetases (VLCSs) capable of activating fatty acids
      with a chain length of 22 or more carbons. Decreased peroxisomal VLCS activity
      is, in part, responsible for the biochemical pathology in X-linked
      adrenoleukodystrophy (X-ALD), illustrating the importance of VLCSs in cellular
      fatty acid homeostasis. We previously cloned two human genes encoding proteins
      homologous to rat peroxisomal VLCS; one (hVLCS) is the human ortholog to the rat 
      VLCS gene and another (hVLCS-H1) encodes a related heart-specific protein. Here, 
      we report the cloning of a third gene (hVLCS-H2) and characterization of its
      protein product. The hVLCS-H2 gene is located on human chromosome 19 and encodes 
      a 690-amino-acid protein. The amino acid sequence of hVLCS-H2 is 44-45% identical
      and 67-69% similar to those of both hVLCS and hVLCS-H1. COS-1 cells transiently
      overexpressing hVLCS-H2 activated the very-long-chain fatty acid lignocerate
      (C24:0) at a rate >1.5-fold higher than that of nontransfected cells (P < 0.002).
      The hVLCS-H2-dependent activation of long- and branched-chain fatty acids
      following transient transfection was less striking. However, hVLCS-H2-dependent
      acyl-CoA synthetase activity with long- and very-long-chain fatty acid substrates
      was detected in COS-1 cells stably expressing hVLCS-H2. For all substrates tested
      (C18:0, C20:0, C24:0, C26:0), the hVLCS-H2 catalyzed activity was significantly
      increased (P < 0.01 to P < 0.0001). By both Northern analysis and reverse
      transcription polymerase chain reaction, hVLCS-H2 is expressed primarily in
      liver. Indirect immunofluorescence of COS-1 cells or human hepatoma-derived HepG2
      cells expressing epitope-tagged hVLCS-H2 revealed that the protein was associated
      with the endoplasmic reticulum but not with peroxisomes. Thus, the primary role
      of hVLCS-H2 is likely to be in fatty acid elongation or complex lipid synthesis
      rather than in degradation.
CI  - Copyright 1999 Academic Press.
FAU - Steinberg, S J
AU  - Steinberg SJ
AD  - Kennedy Krieger Institute and Department of Neurology, Johns Hopkins University
      School of Medicine, Baltimore, Maryland 21205, USA.
FAU - Wang, S J
AU  - Wang SJ
FAU - McGuinness, M C
AU  - McGuinness MC
FAU - Watkins, P A
AU  - Watkins PA
LA  - eng
SI  - GENBANK/AF064255
GR  - HD10981/HD/NICHD NIH HHS/United States
GR  - NS10533/NS/NINDS NIH HHS/United States
GR  - NS37355/NS/NINDS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Genet Metab
JT  - Molecular genetics and metabolism
JID - 9805456
RN  - 0 (DNA, Complementary)
RN  - 0 (Isoenzymes)
RN  - 0 (Repressor Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 63231-63-0 (RNA)
RN  - EC 6.2.1.- (Coenzyme A Ligases)
RN  - EC 6.2.1.3 (FAA2 protein, S cerevisiae)
RN  - EC 6.2.1.3 (long-chain-fatty-acid-CoA ligase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Blotting, Northern
MH  - COS Cells
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 19/genetics
MH  - Cloning, Molecular
MH  - Coenzyme A Ligases/*genetics/metabolism
MH  - DNA, Complementary/chemistry/genetics
MH  - Endoplasmic Reticulum/chemistry
MH  - Fluorescent Antibody Technique, Indirect
MH  - Humans
MH  - Isoenzymes/genetics/metabolism
MH  - Liver/*enzymology
MH  - Microbodies/chemistry
MH  - Molecular Sequence Data
MH  - RNA/genetics/metabolism
MH  - *Repressor Proteins
MH  - *Saccharomyces cerevisiae Proteins
MH  - Sequence Analysis, DNA
MH  - Tissue Distribution
MH  - Tumor Cells, Cultured
EDAT- 1999/09/10 00:00
MHDA- 1999/09/10 00:01
CRDT- 1999/09/10 00:00
PHST- 1999/09/10 00:00 [pubmed]
PHST- 1999/09/10 00:01 [medline]
PHST- 1999/09/10 00:00 [entrez]
AID - 10.1006/mgme.1999.2883 [doi]
AID - S1096-7192(99)92883-4 [pii]
PST - ppublish
SO  - Mol Genet Metab. 1999 Sep;68(1):32-42. doi: 10.1006/mgme.1999.2883.