Linked Life Data

12882974

Source:http://linkedlifedata.com/resource/pubmed/id/12882974

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
41
pubmed:dateCreated
2003-10-6
pubmed:abstractText
The possibility that human cells contain, in addition to the cytosolic type I fatty acid synthase complex, a mitochondrial type II malonyl-CoA-dependent system for the biosynthesis of fatty acids has been examined by cloning, expressing, and characterizing two putative components. Candidate coding sequences for a malonyl-CoA:acyl carrier protein transacylase (malonyltransferase) and its acyl carrier protein substrate, identified by BLAST searches of the human sequence data base, were located on nuclear chromosomes 22 and 16, respectively. The encoded proteins localized exclusively in mitochondria only when the putative N-terminal mitochondrial targeting sequences were present as revealed by confocal microscopy of HeLa cells infected with appropriate green fluorescent protein fusion constructs. The mature, processed forms of the mitochondrial proteins were expressed in Sf9 cells and purified, the acyl carrier protein was converted to the holoform in vitro using purified human phosphopantetheinyltransferase, and the functional interaction of the two proteins was studied. Compared with the dual specificity malonyl/acetyltransferase component of the cytosolic type I fatty acid synthase, the type II mitochondrial counterpart exhibits a relatively narrow substrate specificity for both the acyl donor and acyl carrier protein acceptor. Thus, it forms a covalent acyl-enzyme complex only when incubated with malonyl-CoA and transfers exclusively malonyl moieties to the mitochondrial holoacyl carrier protein. The type II acyl carrier protein from Bacillus subtilis, but not the acyl carrier protein derived from the human cytosolic type I fatty acid synthase, can also function as an acceptor for the mitochondrial transferase. These data provide compelling evidence that human mitochondria contain a malonyl-CoA/acyl carrier protein-dependent fatty acid synthase system, distinct from the type I cytosolic fatty acid synthase, that resembles the type II system present in prokaryotes and plastids. The final products of this system, yet to be identified, may play an important role in mitochondrial function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
40067-74
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12882974-Acyl Carrier Protein, pubmed-meshheading:12882974-Acyl-Carrier Protein S-Malonyltransferase, pubmed-meshheading:12882974-Acyltransferases, pubmed-meshheading:12882974-Animals, pubmed-meshheading:12882974-Base Sequence, pubmed-meshheading:12882974-Cell Line, pubmed-meshheading:12882974-Cloning, Molecular, pubmed-meshheading:12882974-DNA, Complementary, pubmed-meshheading:12882974-Fatty Acid Synthetase Complex, pubmed-meshheading:12882974-Green Fluorescent Proteins, pubmed-meshheading:12882974-HeLa Cells, pubmed-meshheading:12882974-Humans, pubmed-meshheading:12882974-Luminescent Proteins, pubmed-meshheading:12882974-Malonyl Coenzyme A, pubmed-meshheading:12882974-Mitochondria, pubmed-meshheading:12882974-Phylogeny, pubmed-meshheading:12882974-Protein Structure, Tertiary, pubmed-meshheading:12882974-Recombinant Fusion Proteins, pubmed-meshheading:12882974-Recombinant Proteins
pubmed:year
2003
pubmed:articleTitle
Cloning, expression, characterization, and interaction of two components of a human mitochondrial fatty acid synthase. Malonyltransferase and acyl carrier protein.
pubmed:affiliation
Children's Hospital Oakland Research Institute, Oakland, California 94609.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't