Catechin gallates are NADP+-competitive inhibitors of glucose-6-phosphate dehydrogenase and other enzymes that employ NADP+ as a coenzyme

Shin, Eui Seok; Park, Jiyoung; Shin, Jeeyoung; Cho, Dooho; Cho, Si Young; Shin, Dong Wook; Ham, Mira; Kim, Jae Bum; Lee, Tae Ryong

doi:10.1016/j.bmc.2008.02.030

Cited by 52 publications

(44 citation statements)

References 30 publications

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“…To verify this interpretation, we explored the impact of epigallocatechin gallate (EGCG) on the NAD(P)H FLIM parameters. EGCG is a potent competitive inhibitor of NADPH binding30 with no effect on NADH binding indicated by the BRENDA database31. Preferential competition for NADPH-binding sites by EGCG would decrease the bound NADPH population, leaving the bound NADH population unaffected.…”

Section: Resultsmentioning

confidence: 99%

Separating NADH and NADPH fluorescence in live cells and tissues using FLIM

et al. 2014

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NAD is a key determinant of cellular energy metabolism. In contrast, its phosphorylated form, NADP, plays a central role in biosynthetic pathways and antioxidant defence. The reduced forms of both pyridine nucleotides are fluorescent in living cells but they cannot be distinguished, as they are spectrally identical. Here, using genetic and pharmacological approaches to perturb NAD(P)H metabolism, we find that fluorescence lifetime imaging (FLIM) differentiates quantitatively between the two cofactors. Systematic manipulations to change the balance between oxidative and glycolytic metabolism suggest that these states do not directly impact NAD(P)H fluorescence decay rates. The lifetime changes observed in cancers thus likely reflect shifts in the NADPH/NADH balance. Using a mathematical model, we use these experimental data to quantify the relative levels of NADH and NADPH in different cell types of a complex tissue, the mammalian cochlea. This reveals NADPH-enriched populations of cells, raising questions about their distinct metabolic roles.

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Section: Resultsmentioning

confidence: 99%

Separating NADH and NADPH fluorescence in live cells and tissues using FLIM

et al. 2014

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“…Because both classes have disadvantages (e.g., neurotoxicity for 6-AN and a lack of specificity for androsterone derivatives), new inhibitors of both groups are under evaluation to obtain pharmacological agents that modulate G6PD activity with tissue-specific and enzyme-specific targeting [31]. Among natural products, catechin gallates [32] and rosmarinic acid [33] have been recently discovered as inhibitors of G6PD and may represent the next generation of PPP inhibitors.…”

Section: The Oxidative Branch Of the Ppp And Its Regulation In Mammalmentioning

confidence: 99%

The pentose phosphate pathway: An antioxidant defense and a crossroad in tumor cell fate

Riganti

Gazzano

Polimeni

et al. 2012

Free Radical Biology and Medicine

338

289

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“…Knockdown caused a 3-fold decrease in NADPH concentration relative to control cells and was associated with an enzyme-bound NAD(P)H lifetime of 2.7 ns, whereas overexpression caused a 4- to 5-fold increase in NADPH relative to control and an increase in the lifetime of enzyme bound NAD(P)H to 3.8 ns. Selectively unbinding NADPH from its enzymes by exposure to the competitive inhibitor epigallocatechin gallate (EGCG) decreased the lifetime in the overexpressing cells back to 3.1 ns [182]. As altered NAD kinase expression caused little effect on NADH levels [87], these data implied that intracellular bound NADPH shows a significantly longer fluorescence lifetime than bound NADH.…”

Section: Practical Application Of Live-cell Nad(p)h Fluorescencementioning

confidence: 99%

Investigating mitochondrial redox state using NADH and NADPH autofluorescence

Blacker

Duchen

2016

Free Radical Biology and Medicine

286

276

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The redox states of the NAD and NADP pyridine nucleotide pools play critical roles in defining the activity of energy producing pathways, in driving oxidative stress and in maintaining antioxidant defences. Broadly speaking, NAD is primarily engaged in regulating energy-producing catabolic processes, whilst NADP may be involved in both antioxidant defence and free radical generation. Defects in the balance of these pathways are associated with numerous diseases, from diabetes and neurodegenerative disease to heart disease and cancer. As such, a method to assess the abundance and redox state of these separate pools in living tissues would provide invaluable insight into the underlying pathophysiology. Experimentally, the intrinsic fluorescence of the reduced forms of both redox cofactors, NADH and NADPH, has been used for this purpose since the mid-twentieth century. In this review, we outline the modern implementation of these techniques for studying mitochondrial redox state in complex tissue preparations. As the fluorescence spectra of NADH and NADPH are indistinguishable, interpreting the signals resulting from their combined fluorescence, often labelled NAD(P)H, can be complex. We therefore discuss recent studies using fluorescence lifetime imaging microscopy (FLIM) which offer the potential to discriminate between the two separate pools. This technique provides increased metabolic information from cellular autofluorescence in biomedical investigations, offering biochemical insights into the changes in time-resolved NAD(P)H fluorescence signals observed in diseased tissues.

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Catechin gallates are NADP+-competitive inhibitors of glucose-6-phosphate dehydrogenase and other enzymes that employ NADP+ as a coenzyme

Cited by 52 publications

References 30 publications

Separating NADH and NADPH fluorescence in live cells and tissues using FLIM

Separating NADH and NADPH fluorescence in live cells and tissues using FLIM

The pentose phosphate pathway: An antioxidant defense and a crossroad in tumor cell fate

Investigating mitochondrial redox state using NADH and NADPH autofluorescence

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