Biosynthetic Pathway to the Cancer Chemopreventive Secoisolariciresinol Diglucoside−Hydroxymethyl Glutaryl Ester-Linked Lignan Oligomers in Flax (Linum usitatissimum) Seed

Ford, Joshua D.; Huang, Kuan‐Tsae; Wang, Huaibin; Davin, Laurence B.; Lewis, Norman G.

doi:10.1021/np010367x

Cited by 143 publications

(49 citation statements)

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“…(Westcott and Muir, 1996a). Also It had been suggested that p-coumaric acid and ferulic acid glucosides were linked directly via ester linkage of their carboxyl groups to the glucosyl moiety of SDG as a terminal unit in SDG oligomers (Struijset al,2008) and were easily released by alkaline hydrolysis (Johnssonet al,2002;Ford et al,2001). The step followed by extraction is hydrolysis.…”

Section: Resultsmentioning

confidence: 99%

“…The level of SDG in flaxseed, 1-4% (w/w) (Eliassonet al, 2003), is 60-700 times higher than that in other edible plant parts (Ford et al, 2001).Variation in flaxseed lignan concentrations depend on the variety, location, and crop year (Westcott and Muir,1996b).Secoisolariciresinol (SECO) amount found in foods. Whole seed and ground flax typically contain between 0.7% and 1.9% SDG, which is approximately 77 to 209 mg SDG/tbsp of whole seed or 56 to 152 mg SDG/tbsp of ground flaxseed (Morris, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Isolation and Purification of Secoisolariciresinoldiglucoside oligomers (Lignan) from Flax seed and its evaluation of antioxidant activity

Al-Jumaily¹

2013

IOSR-JAC

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Isolation and Purification of Secoisolariciresinoldiglucoside oligomers (Lignan) from Flax seed and its evaluation of antioxidant activity

Al-Jumaily¹

2013

IOSR-JAC

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“…Cofactor Binding-As in other NAD(P)H dependent reductases, PCBER_Pt1, PLR_Tp1, and IFR_Ms1 have completely conserved 11 GXXGXXG 19 (NAD(P)H-binding motif) sequences (Fig. 3A, highlighted in red) at the first ␤-␣-␤ unit.…”

Section: Resultsmentioning

confidence: 99%

“…For example, PLRs, which catalyze reduction of the 8 -8Ј linked lignan pinoresinol (Scheme 1, structure 1) (6,10), generate the precursors of cancer-preventative natural products, such as secoisolariciresinol diglucoside (structure 2) derivatives in flaxseed (Linum usitatissimum) (11,12) and matairesinol (structure 3)/secoisolariciresinol (structure 4) in a wide variety of plant species (5,11,13). Such lignans are considered to be metabolized in mammals into the cancer-preventing "mammalian" lignans, enterodiol (structure 5) and enterolactone (structure 6), with the latter metabolites being generated in the gut by the action of gastrointestinal flora such as Clostridia sp (14,15).…”

mentioning

confidence: 99%

Crystal Structures of Pinoresinol-Lariciresinol and Phenylcoumaran Benzylic Ether Reductases and Their Relationship to Isoflavone Reductases

Min

Kasahara

Bedgar

et al. 2003

Journal of Biological Chemistry

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Despite the importance of plant lignans and isoflavonoids in human health protection (e.g. for both treatment and prevention of onset of various cancers) as well as in plant biology (e.g. in defense functions and in heartwood development), systematic studies on the enzymes involved in their biosynthesis have only recently begun. In this investigation, three NADPH-dependent aromatic alcohol reductases were comprehensively studied, namely pinoresinol-lariciresinol reductase (PLR), phenylcoumaran benzylic ether reductase (PCBER), and isoflavone reductase (IFR), which are involved in central steps to the various important bioactive lignans and isoflavonoids. Of particular interest was in determining how differing regio-and enantiospecificities are achieved with the different enzymes, despite each apparently going through similar enone intermediates. Initially, the three-dimensional x-ray crystal structures of both PLR_Tp1 and PCBER_Pt1 were solved and refined to 2.5 and 2.2 Å resolutions, respectively. Not only do they share high gene sequence similarity, but their structures are similar, having a continuous ␣/␤ NADPH-binding domain and a smaller substrate-binding domain. IFR (whose crystal structure is not yet obtained) was also compared (modeled) with PLR and PCBER and was deduced to have the same overall basic structure. The basis for the distinct enantio-specific and regio-specific reactions of PCBER, PLR, and IFR, as well as the reaction mechanism and participating residues involved (as identified by site-directed mutagenesis), are discussed.

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“…However, in certain other plant species, such as flax (Linum usitatissimum), the opposite stereoselective and enantiospecific transformations can predominate (16,19,20,42), i.e. whereby (Ϫ)-pinoresinol (11b) is preferentially formed and then metabolized into (Ϫ)-lariciresinol (12b) and (ϩ)-secoisolariciresinol (2b), respectively.…”

mentioning

confidence: 99%

Crystal Structures of Apo-form and Binary/Ternary Complexes of Podophyllum Secoisolariciresinol Dehydrogenase, an Enzyme Involved in Formation of Health-protecting and Plant Defense Lignans

Youn

Moinuddin

Davin

et al. 2005

Journal of Biological Chemistry

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(؊)-Matairesinol is a central biosynthetic intermediate to numerous 8 -8-lignans, including the antiviral agent podophyllotoxin in Podophyllum species and its semi-synthetic anticancer derivatives teniposide, etoposide, and Etopophos®. It is formed by action of an enantiospecific secoisolariciresinol dehydrogenase, an NAD(H)-dependent oxidoreductase that catalyzes the conversion of (؊)-secoisolariciresinol. Matairesinol is also a plant-derived precursor of the cancerpreventative "mammalian" lignan or "phytoestrogen" enterolactone, formed in the gut following ingestion of high fiber dietary foodstuffs, for example. Additionally, secoisolariciresinol dehydrogenase is involved in pathways to important plant defense molecules, such as plicatic acid in the western red cedar (Thuja plicata) heartwood. To understand the molecular and enantiospecific basis of Podophyllum secoisolariciresinol dehydrogenase, crystal structures of the apo-form and binary/ternary complexes were determined at 1.6, 2.8, and 2.0 Å resolution, respectively. The enzyme is a homotetramer, consisting of an ␣/␤ single domain monomer containing seven parallel ␤-strands flanked by eight ␣-helices on both sides. Its overall monomeric structure is similar to that of NAD(H)-dependent shortchain dehydrogenases/reductases, with a conserved Asp 47 forming a hydrogen bond with both hydroxyl groups of the adenine ribose of NAD(H), and thus specificity toward NAD(H) instead of NADP(H). The highly conserved catalytic triad (Ser 153 , Tyr 167 , and Lys 171 ) is adjacent to both NAD ؉ and substrate molecules, where Tyr 167 functions as a general base. Following analysis of high resolution structures of the apo-form and two complex forms, the molecular basis for both the enantio-specificity and the reaction mechanism of secoisolariciresinol dehydrogenase is discussed and compared with that of pinoresinol-lariciresinol reductase.

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Biosynthetic Pathway to the Cancer Chemopreventive Secoisolariciresinol Diglucoside−Hydroxymethyl Glutaryl Ester-Linked Lignan Oligomers in Flax (Linum usitatissimum) Seed

Cited by 143 publications

References 46 publications

Isolation and Purification of Secoisolariciresinoldiglucoside oligomers (Lignan) from Flax seed and its evaluation of antioxidant activity

Isolation and Purification of Secoisolariciresinoldiglucoside oligomers (Lignan) from Flax seed and its evaluation of antioxidant activity

Crystal Structures of Pinoresinol-Lariciresinol and Phenylcoumaran Benzylic Ether Reductases and Their Relationship to Isoflavone Reductases

Crystal Structures of Apo-form and Binary/Ternary Complexes of Podophyllum Secoisolariciresinol Dehydrogenase, an Enzyme Involved in Formation of Health-protecting and Plant Defense Lignans

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