Flavonoids transport

Marinova K, Kleinschmidt K, Weissenbock G, Klein M. 2007b. Flavonoid biosynthesis in barley primary leaves requires the presence of the vacuole and controls the activity of vacuolar flavonoid transport. Plant Physiol 144 432-A44. 

Figure 19.2 Sortinl affects flavonoid transport to the vacuole, (a) Seed coat colors of different slh mutants, (b) DMACA staining shows that some slh mutants (2-50, 2-21, and 10-27) have defects in vacuolar accumulation of proanthocyanidins in the seed coats, (c-e) The recessive mutant slh2-50 is allelic to tt4, a flavonoid biosynthesis mutant that also affects vacuole morphology. The localization of EGFP-5TIP in...

Sortinl affects the vacuolar trafficking of both proteins and flavonoids, indicating that flavonoid transport to the vacuole could share the same membrane-mediated pathway as vacuolar proteins. But this does not rule out the possibility that one of the trafficking defects is direct, whereas the other one is indirect. The fact that Sortinl mimics BSO to produce an oxidized cell environment to affect ABC transporter activity supports a model that a transporter-mediated flavonoid transport defect induces miss-trafficking of other vacuolar contents such as the proteins. On the other hand, mutants defective in flavonoid metabolism, such as tt4, show hypersensitivity to Sortinl and have altered vacuolar morphology... 

Sortinl decomposes in plant growth media where one of the products resembles the effects of BSO, a GSH biosynthesis inhibitor. This indicates that a series of observed Sortinl effects might be due to an oxidized cellular environment that it creates. It could be that Sortinl or an active decomposition product sequesters GSH or inhibits GSH production. This may induce the transcription of cytochrome P450-dependent monooxygenases and mixed function oxidases, as shown in the transcription profile after Sortinl treatment. Reduced GSH level then affects flavonoid transport. 

Milbury PE, Kalt W (2010) Xenobiotic metabolism and berry flavonoid transport across the blood-brain barrier. J Agric Food Chem 58(7) 3950-3956. doi 10.1021/jf903529m... 

Rotenone is a complex flavonoid found in the plant Derris ellyptica. It acts by inhibiting electron transport in the mitochondrion. Derris powder is an insecticidal preparation made from the plant, which is highly toxic to hsh. 

Rotenone A complex flavonoid produced by the plant Denis ellyptica. It has insecticidal activity due to its ability to inhibit electron transport in the mitochondrion. 

Allelopathic inhibition of mineral uptake results from alteration of cellular membrane functions in plant roots. Evidence that allelochemicals alter mineral absorption comes from studies showing changes in mineral concentration in plants that were grown in association with other plants, with debris from other plants, with leachates from other plants, or with specific allelochemicals. More conclusive experiments have shown that specific allelochemicals (phenolic acids and flavonoids) inhibit mineral absorption by excised plant roots. The physiological mechanism of action of these allelochemicals involves the disruption of normal membrane functions in plant cells. These allelochemicals can depolarize the electrical potential difference across membranes, a primary driving force for active absorption of mineral ions. Allelochemicals can also decrease the ATP content of cells by inhibiting electron transport and oxidative phosphorylation, which are two functions of mitochondrial membranes. In addition, allelochemicals can alter the permeability of membranes to mineral ions. Thus, lipophilic allelochemicals can alter mineral absorption by several mechanisms as the chemicals partition into or move through cellular membranes. Which mechanism predominates may depend upon the particular allelochemical, its concentration, and environmental conditions (especially pH). 

Effects of Allelochemlcals on ATPases. Several flavonoid compounds inhibit ATPase activity that is associated with mineral absorption. Phloretin and quercetin (100 pM) inhibited the plasma membrane ATPase Isolated from oat roots (33). The naphthoquinone juglone was inhibitory also. However, neither ferulic acid nor salicylic acid inhibited the ATPase. Additional research has shown that even at 10 mM salicylic acid inhibits ATPase activity only 10-15% (49). This lack of activity by salicylic acid was substantiated with the plasma membrane ATPase Isolated from Neurospora crassa (50) however, the flavonols fisetln, morin, myricetin, quercetin, and rutin were inhibitory to the Neurospora ATPase. Flavonoids inhibited the transport ATPases of several animal systems also (51-53). Thus, it appears that flavonoids but not phenolic acids might affect mineral transport by inhibiting ATPase enzymes. 

Although several allelochemicals (primarily phenolic acids and flavonoids) have been shown to inhibit mineral absorption, only the phenolic acids have been studied at the physiological and biochemical levels to attempt to determine if mineral transport across cellular membranes can be affected directly rather than indirectly. Similar and even more definitive experiments need to be conducted with other allelochemicals that are suspected of inhibiting mineral absorption. Membrane vesicles isolated from plant cells are now being used to elucidate the mechanism of mineral transport across the plasma membrane and tonoplast (67, 68). Such vesicle systems actively transport mineral ions and thus can serve as simplified systems to directly test the ability of allelochemicals to inhibit mineral absorption by plant cells. 

Walle, U. K., Galijatovic, A., Walle, T., Transport of the flavonoid chrysin and its conjugated metabolites by the human intestinal cell line Caco-2, Biochem. Pharmacol. 1999, 58, 431-438. 

Another area in which Arabidopsis genetics is proving to be useful is the study of the proposed role of flavonoids in regulating auxin transport. Several years ago, Jacobs and Rubery published the first evidence that flavonoids could specifically compete with naphthylphthalamic acid for binding to the auxin efflux carrier in etiolated zucchini hypocotyls.35 This finding was somewhat controversial, however, and no additional evidence for the connection between flavonoids and auxin transport was reported for some time. Brown et al. have now used Arabidopsis flavonoid mutants to generate new evidence in support of a role for flavonoids in the regulation of polar auxin movement.6 These experiments took... 

M., The TRANSPARENT TESTA12 gene of Arabidopsis encodes a multidrug secondary transporter-like protein required for flavonoid sequestration in vacuoles of the seed coat endothelium, Plant Cell, 2001,13, 853-871. 

S. Zhang, X. Yang, and M.E. Morris. Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport. Mol Pharmacol. 65 1208-1216... 

Passamonti S, Terdoslavich M, Franca R, Vanzo A, TramerF, Braidot E, Petrussa E, Vianello A (2009) Bioavailability of flavonoids a review of their membrane transport and the function of bilitranslocase in animal and plant organisms. Curr Drug Metab 10 369-394... 

The objectives of the studies reported herein were to (a) compare the effects of a series of phenolic acids, coumarins, and flavonoids on whole chain electron transport and phosphorylation in Isolated plant chloroplasts and mitochondria and (b) identify specific sites of inhibition with polarographic and enzymatic techniques. Exploratory studies were conducted with the 20 compounds listed in Table I. The three glycosides are shown indented below the corresponding aglycones. Detailed studies were conducted with the six compounds, one representative member from each chemical family, designated with an asterisk. 

A publication that nicely complements this review is Chang s account of pharmacophore-based in silico models [101] which, in addition to P-gp, is dedicated to the other two major efflux pumps MRPl and BCRP. Unfortunately the most recent nonpharmacophoric in silico modeling efforts around the latter transporters are solely based on flavonoid compounds, which limits the applicability of their conclusions [102, 103]. 

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