Role of Acyl-CoA Binding Protein in Acyl-CoA Metabolism and Acyl-CoA–Mediated Cell Signaling

Knudsen, Jens; Neergaard, Thomas B. F.; Gaigg, Barbara; Jensen, Mette V.; Hansen, Janne Hedegaard

doi:10.1093/jn/130.2.294s

Cited by 150 publications

(125 citation statements)

References 46 publications

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“…More recent data with fluorescent fatty acyl-CoAs in living cells has confirmed the earlier prediction that nuclearplasmic concentrations of fatty acyl-CoAs were indeed less than 10nM (17). However, this concentration can be increased several-fold by expression of cytoplasmic fatty acyl-CoA binding proteins (49,50). Thus, the CoA thioesters of VLCFA and BCFA are nearly all bound with affinities in the physiological range of fatty acyl-CoA concentrations in the nucleoplasm of living cells.…”

Section: Discussionsupporting

confidence: 56%

Very-Long-Chain and Branched-Chain Fatty Acyl-CoAs Are High Affinity Ligands for the Peroxisome Proliferator-Activated Receptor α (PPARα)

2006

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Very long chain fatty acids (VLCFA) and branched-chain fatty acids (BCFA) are potent inducers of the peroxisome proliferator-activated receptor PPARα, a nuclear receptor that enhances transcription of peroxisomal enzymes mediating β-oxidation of these potentially toxic fatty acids. However, it is not known whether the respective free fatty acids or their activated metabolites, i.e. CoA thioesters: (i) are the endogenous high-affinity PPARα ligands, (ii) alter PPARα conformation, and (iii) alter recruitment of coregulatory proteins to PPARα. As shown by quenching of PPARα intrinsic amino acid fluorescence, PPARα exhibited high affinity (3-29nM K d s) for the CoA thioesters of the common (C20-C24) VLCFA. In contrast, with the exception of arachidonic acid (K d =20nM), PPARα only weakly bound the VLCFA. PPARα also exhibited higher affinity for the CoA thioesters of BCFA (phytanoyl-CoA, pristanoyl-CoA; K d s near 11nM) than for the respective free branched-chain fatty acids. As shown by circular dichroism, the high affinity VLCFA-CoA and BCFA-CoA strongly altered PPARα conformation. Likewise, the high affinity VLCFA-CoA and BCFA-CoA altered cofactor recruitment to PPARα as shown by co-immunoprecipitation from liver homogenates. In contrast, nearly all the respective free fatty acids elicited only weak conformational changes in PPARα and did not alter co-factor recruitment to PPARα. In summary, the CoA thioesters of verylong-chain and branched-chain fatty acids are much more potent PPARα ligands than the free acids, resulting in altered PPARα conformation and cofactor recruitment. Since these are hallmarks of ligands-activated nuclear receptors, this suggests that the CoA thioesters are the active forms of these PPARα ligands.

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Section: Discussionsupporting

confidence: 56%

Very-Long-Chain and Branched-Chain Fatty Acyl-CoAs Are High Affinity Ligands for the Peroxisome Proliferator-Activated Receptor α (PPARα)

2006

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“…However, there are a number of long-type ACBPs that are fused with ankyrin repeats, such as ACBP1 and ACBP2 in A. thaliana (Chye et al, 1999;Li & Chye, 2003), or with other functional domains, such as the human peroxisomal D3, D2-enoyl-CoA isomerase (Geisbrecht et al, 1999). ACBP mainly functions as an intracellular acyl-CoA transporter and pool former, and is critical to lipid metabolism in cells (Gossett et al, 1996;Knudsen et al, 2000;Schroeder et al, 1998). However, ACBP has only been found in eukaryotes, not in prokaryotes except for a few pathogenic eubacteria that might have acquired ACBP from eukaryotic hosts via lateral gene transfer (Burton et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Functional characterization of a fatty acyl-CoA-binding protein (ACBP) from the apicomplexan Cryptosporidium parvum

2006

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In this paper, the identification and functional analysis of a fatty acyl-CoA-binding protein (ACBP) gene from the opportunistic protist Cryptosporidium parvum are described. The CpACBP1 gene encodes a protein of 268 aa that is three times larger than typical ACBPs (i.e. ∼90 aa) of humans and animals. Sequence analysis indicated that the CpACBP1 protein consists of an N-terminal ACBP domain (∼90 aa) and a C-terminal ankyrin repeat sequence (∼170 aa). The entire CpACBP1 ORF was engineered into a maltose-binding protein fusion system and expressed as a recombinant protein for functional analysis. Acyl-CoA-binding assays clearly revealed that the preferred binding substrate for CpACBP1 is palmitoyl-CoA. RT-PCR, Western blotting and immunolabelling analyses clearly showed that the CpACBP1 gene is mainly expressed during the intracellular developmental stages and that the level increases during parasite development. Immunofluorescence microscopy showed that CpACBP1 is associated with the parasitophorous vacuole membrane (PVM), which implies that this protein may be involved in lipid remodelling in the PVM, or in the transport of fatty acids across the membrane.

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“…The total cellular concentration of LCFA-CoA is between 5-160 M, depending on cell and tissue type (9,10). However, since LCFA-CoAs readily partition into membranes and/or interact with a variety of intracellular LCFA-CoA binding proteins, the free unbound LCFA-CoA pool is in the low nM range and unlikely to exceed 200 nM (10).…”

mentioning

confidence: 99%

ACBP and cholesterol differentially alter fatty acyl CoA utilization by microsomal ACAT

Chao

Zhou

McIntosh

et al. 2003

Journal of Lipid Research

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Role of Acyl-CoA Binding Protein in Acyl-CoA Metabolism and Acyl-CoA–Mediated Cell Signaling

Cited by 150 publications

References 46 publications

Very-Long-Chain and Branched-Chain Fatty Acyl-CoAs Are High Affinity Ligands for the Peroxisome Proliferator-Activated Receptor α (PPARα)

Very-Long-Chain and Branched-Chain Fatty Acyl-CoAs Are High Affinity Ligands for the Peroxisome Proliferator-Activated Receptor α (PPARα)

Functional characterization of a fatty acyl-CoA-binding protein (ACBP) from the apicomplexan Cryptosporidium parvum

ACBP and cholesterol differentially alter fatty acyl CoA utilization by microsomal ACAT

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