Green Tea Epigallocatechin Gallate: A Natural Inhibitor of Fatty-Acid Synthase

Wang, Xuan; Tian, Wei-Xi

doi:10.1006/bbrc.2001.5923

Cited by 167 publications

(133 citation statements)

References 14 publications

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“…Possibly, the structural resemblances made chlorogenic acid and EGCG bind competitively at the NADPH-binding site on the enzyme. In addition, EGCG was able to inhibit irreversibly the b-ketoacyl reductase of FAS I, and the ester bond of EGCG played a critical role in the inactivation (15). Chlorogenic acid also contained a similar ester bond, but it was found that after 1 mM chlorogenic acid was mixed with FAS I, it did not show the obviously irreversible inhibition within 2 h (data not shown).…”

Section: Resultsmentioning

confidence: 96%

“…All these inhibitory kinetic behaviors of FabG were similar to those of the b-ketoacyl reductase domain of FAS I, and both inhibitions by chlorogenic acid were highly associated with NADPH, indicative of that chlorogenic acid could, or partially, simulate NADPH to bind to the enzyme. Among the reported FAS inhibitors, epigallocatechin gallate (EGCG) and analogues could also inhibit both FAS I and FabG, and the inhibitions were related to NADPH (15,35). EGCG inhibited the b-ketoacyl reductase of FAS I competitively against NADPH with IC50 of about 100 mM, and almost showed the same inhibitory activity as chlorogenic acid (15).…”

Section: Resultsmentioning

confidence: 99%

“…Among the reported FAS inhibitors, epigallocatechin gallate (EGCG) and analogues could also inhibit both FAS I and FabG, and the inhibitions were related to NADPH (15,35). EGCG inhibited the b-ketoacyl reductase of FAS I competitively against NADPH with IC50 of about 100 mM, and almost showed the same inhibitory activity as chlorogenic acid (15). From their molecular structures (Fig.…”

Section: Resultsmentioning

confidence: 99%

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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: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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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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“…After the enzyme solutions were mixed with various concentrations of inhibitors, aliquots were taken to measure the relative activity at the indicated time intervals to measure slow-binding inactivation. 6 Substrate Protection GE was added to FAS solutions mixed with one of three substrates respectively, and then the relative activities of FAS at different time intervals were measured. The same concentration of GE and FAS solutions without any substrate added was used as the control.…”

Section: Assay Of Fas Activitymentioning

confidence: 99%

Presence of Fatty Acid Synthase Inhibitors in the Rhizome ofAlpinia officinarumHance

Tian

2003

Journal of Enzyme Inhibition and Medicinal Chemistry

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The galangal (the rhizome of Alpinia officinarum, Hance) is popular in Asia as a traditional herbal medicine. The present study reports that the galangal extract (GE) can potently inhibit fatty-acid synthase (FAS, E.C.2.3.1.85). The inhibition consists of both reversible inhibition with an IC 50 value of 1.73 mg dried GE/ml, and biphasic slow-binding inactivation. Subsequently the reversible inhibition and slow-binding inactivation to FAS were further studied. The inhibition of FAS by galangin, quercetin and kaempferol, which are the main flavonoids existing in the galangal, showed that quercetin and kaempferol had potent reversible inhibitory activity, but all three flavonoids had no obvious slow-binding inactivation. Analysis of the kinetic results led to the conclusion that the inhibitory mechanism of GE is totally different from that of some other previously reported inhibitors of FAS, such as cerulenin, EGCG (epigallocatechin gallate) and C75.

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“…Recently, an in vitro study has shown that EGCG is an effective inhibitor of FAS isolated from chicken liver. 13 It seems that because most previous studies on the FAS inhibitors have been confined to their inhibitory effects on the enzyme activity of FAS, 5,7,8,14 it would be more interesting to investigate the inhibitory effects of these compounds on the enzyme biosynthesis of FAS. Our previous studies 10 showed that long-term feeding of Chinese Longjing green tea leaves to rats could reduce their body weight and lipid contents without reducing food intake.…”

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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Green Tea Epigallocatechin Gallate: A Natural Inhibitor of Fatty-Acid Synthase

Cited by 167 publications

References 14 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

Presence of Fatty Acid Synthase Inhibitors in the Rhizome ofAlpinia officinarumHance

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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