Tuesday, August 29, 2006
The flavonoid synthetic pathway begins with a product of glycolysis, phosphoenolpyruvate, entering into the Shikimate pathway to yield phenylalanine. Phenylalanine is the starting material of the phenylpropanoid metabolic pathway, from which 4-Coumaryl-CoA is produced. This can be combined with Malonyl-CoA to yield the true backbone of flavonoids, a group of compounds called chalcones. Ring-closure of these compounds results in the familiar form of flavonoids, a three-ringed phenolic structure (polyphenols). The metabolic pathway continues through a series of enzymatic modifications to yield flavanones → dihydroflavonols → anthocyanins. Along this pathway many products can be formed, including the flavonols, flavan-3-ols, proanthocyanidins (tannins) and a host of other polyphenolics.
Flavonoids are widely distributed in plants fulfilling many functions including producing yellow or red/blue pigmentation in flowers and protection from attack by microbes and insects. The widespread distribution of flavonoids, their variety and their relatively low toxicity compared to other active plant compounds (for instance alkaloids) mean that many animals, including humans, ingest significant quantities in their diet. Flavonoids have been found in high concentrations in butterflies and moths sequestered from dietary intake at the larval stage and then stored in adult tissues.
Flavonoids have been referred to as "nature's biological response modifiers" because of strong experimental evidence of their ability to modify the body's reaction to allergens, viruses, and carcinogens. They show anti-allergic, anti-inflammatory, anti-microbial and anti-cancer activity. In addition, flavonoids act as powerful antioxidants, protecting against oxidative and free radical damage.
Consumers and food manufacturers have become interested in flavonoids for their medicinal properties, especially their potential role in the prevention of cancers and cardiovascular disease. The beneficial effects of fruit, vegetables, and tea or even red wine have been attributed to flavonoid compounds rather than to known nutrients and vitamins.
Quercetin is a flavonoid that forms the "backbone" for many other flavonoids, including the citrus flavonoids rutin, hesperidin, naringin and tangeritin. In studies, quercetin is found to be the most active of the flavonoids, and many medicinal plants owe much of their activity to their high quercetin content. Quercetin has demonstrated significant anti-inflammatory activity because of direct inhibition of several initial processes of inflammation. For example, it inhibits both the manufacture and release of histamine and other allergic/inflammatory mediators. In addition, it exerts potent antioxidant activity and vitamin C-sparing action.
Proanthocyanidins extracts demonstrate a wide range of pharmacological activity. Their effects include increasing intracellular vitamin C levels, decreasing capillary permeability and fragility, scavenging oxidants and free radicals, and inhibiting destruction of collagen, the most abundant protein in the body.
Epicatechin improves blood flow and thus seems good for cardiac health. Cocoa, the major ingredient of dark chocolate, is loaded with epicatechin and has been found to have nearly twice the antioxidant content of red wine and up to three times that of green tea.
Important dietary sources
Good sources of flavonoids include all citrus fruits, berries, onions, parsley, legumes, green tea, red wine, seabuckthorn, and dark chocolate (that with a cocoa content of seventy percent or greater).
The citrus bioflavonoids include hesperidin, quercetin, rutin (a sugar of quercetin), and tangeritin. In addition to possessing antioxidant activity and an ability to increase intracellular levels of vitamin C, rutin and hesperidin exert beneficial effects on capillary permeability and blood flow. They also exhibit some of the anti-allergy and anti-inflammatory benefits of quercetin. Quercetin can also inhibit reverse transcriptase, part of the replication process of retroviruses (Spedding et al. 1989). The therapeutical relevance of this inhibition has not been established. Hydroxyethylrutosides (HER) have been used in the treatment of capillary permeability, easy bruising, hemorrhoids, and varicose veins.
Green tea polyphenols are potent antioxidant compounds that have demonstrated greater antioxidant protection than vitamins C and E. Green tea may also increase the activity of antioxidant enzymes. Green tea polyphenols may inhibit cancer by blocking the formation of cancer-causing compounds and suppressing the activation of carcinogens. The major polyphenols in green tea are flavonoids (catechin, epicatechin, epicatechin gallate, epigallocatechin gallate,(EGCG), and proanthocyanidins).
Though both green tea and black tea are derived from the same plant (Camellia sinensis), they possess different antioxidants. In producing black tea the leaves are allowed to oxidize, during which enzymes present in the tea convert many polyphenols to larger molecules with different biological effects. However, green tea is produced by lightly steaming the fresh-cut leaf, which inactivates these enzymes, and oxidation does not occur.
Availability through microorganisms
A number of recent research articles have demonstrated the efficient production of flavonoid molecules from recombinant microorganisms. Such an approach opens the possibility of readily producing these compounds using renewable feedstocks and thus increasing the availability of rare flavonoid molecules for human and animal feed through dietary supplements.