The animal fatty acid synthase: one gene, one polypeptide, seven enzymes

Smith, Stuart

doi:10.1096/fasebj.8.15.8001737

Cited by 556 publications

(481 citation statements)

References 3 publications

(6 reference statements)

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“…The associated system, FAS I, consists of a single large polypeptide that contains multiple active sites, i.e., acetyl/malonyl transferase, b-ketoacyl synthase, b-ketoacyl reductase, b-hydroxyacyl dehydratase, enoyl reductase and thioesterase , and which performs all of the elongation steps in the pathway (2,3). This system mainly exists in animals.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory activity of chlorogenic acid on enzymes involved in the fatty acid synthesis in animals and bacteria

et al. 2006

TBMB

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SummaryIt was found that chlorogenic acid inhibited in vitro animal fatty acid synthase (FAS I) and the b-ketoacyl-ACP reductase (FabG) from Escherichia coli in a concentration-dependent manner with respective IC50 of 94.8 and 88.1 mM. The results of LineweaverBurk plots indicated that chlorogenic acid inhibited competitively the binding of NADPH to FAS I, while left those of acetyl-CoA and malonyl-CoA unaffected. Further kinetic studies showed that chlorogenic acid blocked the activity of FAS I mainly by inhibiting the b-ketoacyl reductase domain, which catalyzed the same reaction as that done by FabG in the fatty acid synthesis. The b-ketoacyl reduction reactions accomplished by both FAS I and FabG required nucleotide cofactor, NADPH. Furthermore, the Lineweaver-Burk and Yonetani-Theorell analyses implicated that chlorogenic acid filled competitively in the binding-pocket of NADPH in the b-ketoacyl reductase domain of FAS I. The similar results were also obtained from the inhibition of FabG by chlorogenic acid. As observed in these results, the inhibitions of FAS I and FabG by chlorogenic acid were highly related to the interference of the inhibitor with NADPH, which was possibly due to the similarity between chlorogenic acid and some portion of NADPH, maybe the section consisting of the two ribose groups.

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Section: Introductionmentioning

confidence: 99%

Inhibitory activity of chlorogenic acid on enzymes involved in the fatty acid synthesis in animals and bacteria

et al. 2006

TBMB

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“…Plants synthesize fatty acids within the plastids, and use a discrete and highly conserved group of dissociated enzymes named fatty acid synthase system type 2 (FASII) [6]. This system, similarily to the eukaryotic mitochondrial FAS [7][8][9][10], differs from the mammalian cytosolic fatty acid synthase system type 1 (FASI) where all reactions are carried out by a single multifunctional polypeptide [11]. Fatty acids synthesized within plastid are exported to endoplasmic reticulum (ER) for elongation, resulting in the formation of VLCFAs that are essential cellular precursors of waxes, seed storage lipids and sphingolipids [5].…”

Section: Introductionmentioning

confidence: 99%

Cloning and functional characterization of two cDNAs encoding NADPH-dependent 3-ketoacyl-CoA reductased from developing cotton fibers

et al. 2005

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Genes encoding enzymes involved in biosynthesis of very long chain fatty acids were significantly up-regulated during early cotton fiber development. Two cDNAs, GhKCR1 and GhKCR2 encoding putative cotton 3-ketoacyl-CoA reductases that catalyze the second step in fatty acid elongation, were isolated from developing cotton fibers. GhKCR1 and 2 contain open reading frames of 963 bp and 924 bp encoding proteins of 320 and 307 amino acid residues, respectively. Quantatitive RT-PCR analysis showed that both these genes were highly preferentially expressed during the cotton fiber elongation period with much lower levels recovered from roots, stems and leaves. GhKCR1 and 2 showed 30%-32% identity to Saccharomyces cerevisiae Ybr159p at the deduced amino acid level. These cotton cDNAs were cloned and expressed in yeast haploid ybr159w∆ mutant that was deficient in 3-ketoacyl-CoA reductase activity. Wild-type growth rate was restored in ybr159w∆ cells that expressed either GhKCR1 or 2. Further analysis showed that GhKCR1 and 2 were co-sedimented within the membranous pellet fraction after high-speed centrifugation, similar to the yeast endoplasmic reticulum marker ScKar2p. Both GhKCR(s) showed NADPH-dependent 3-ketoacyl-CoA reductase activity in an in vitro assay system using palmitoyl-CoA and malonyl-CoA as substrates. Our results suggest that GhKCR1 and 2 are functional orthologues of ScYbr159p.

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“…Fatty acid synthase (FAS) is an important enzyme participating in energy metabolism 3 and is related to various human diseases including obesity, cardiovascular disease and cancer. Human cancer cells express high levels of FAS and inhibition of FAS is selectively cytotoxic to human cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Suppression of fatty acid synthase in MCF-7 breast cancer cells by tea and tea polyphenols: a possible mechanism for their hypolipidemic effects

et al. 2003

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Tea is a heavily consumed beverage world wide because of its unique aroma, less cost and broad availability. Fatty acid synthase (FAS) is a key enzyme in lipogenesis. FAS is overexpressed in the malignant human breast carcinoma MCF-7 cells and its expression is further enhanced by the epidermal growth factor (EGF). The EGF-induced expression of FAS was inhibited by green and black tea extracts. The expression of FAS was also suppressed by the tea polyphenol (À)-epigallocatechin 3-gallate (EGCG), theaflavin (TF-1), TF-2 and theaflavin 3,3 0 -digallate(TF-3) at both protein and mRNA levels that may lead to the inhibition of cell lipogenesis and proliferation. Both EGCG and TF-3 inhibit the activation of Akt and block the binding of Sp-1 to its target site. Furthermore, the EGF-induced biosyntheses of lipids and cell proliferation were significantly suppressed by EGCG and TF-3. These findings suggest that tea polyphenols suppress FAS expression by downregulating EGF receptor/ PI3K/Akt/Sp-1 signal transduction pathway, and tea and tea polyphenols might induce hypolipidemic and antiproliferative effects by suppressing FAS.

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The animal fatty acid synthase: one gene, one polypeptide, seven enzymes

Cited by 556 publications

References 3 publications

Inhibitory activity of chlorogenic acid on enzymes involved in the fatty acid synthesis in animals and bacteria

Inhibitory activity of chlorogenic acid on enzymes involved in the fatty acid synthesis in animals and bacteria

Cloning and functional characterization of two cDNAs encoding NADPH-dependent 3-ketoacyl-CoA reductased from developing cotton fibers

Suppression of fatty acid synthase in MCF-7 breast cancer cells by tea and tea polyphenols: a possible mechanism for their hypolipidemic effects

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