Isoflavones compounds metabolism

Isoflavones undergo metabolic transformation in the gut. Namely, Daid is known to be transformed into o-desmethyl-angolensin and Gen into p-ethylphenol [70] by gut bacteria. These compounds can enter the blood stream but are not estrogenic. In contrast, Daid, can be biotransformed by the gut bacteria into S-equol (S -Eq) [71, 72]. Unlike in humans, this conversion is highly efficient in animal models including mice [73], rats [74], monkeys [75], and hamsters [76], but not in pigs, which seem to be rather close to humans on this point [77]. In human consumers, 5-Eq occurs only in about 20-45% of the tested populations [78]. 

The mucosa of the GIT represents an interface between the external and internal environments. The expansive surface area is necessary for the efficient hydrolysis of foodstuffs and the absorption of energy and nutrients. The mucosa also influences the systemic availability of non-nutrient compounds in the diet, both beneficial and detrimental. Digestion and absorption of glucosinolates are critical determinants of health benefits (see Chapter 4) Similarly, the bioavailability and health benefits of phytoestrogens, such as genistein (see Chapters 5 and 10) are at least partly dependent on the carrier-mediated processes of absorption associated with the GIT (Oitate et al, 2001). Moreover, the metabolic activities of the mucosa can influence the systemic concentrations and forms of dietary phytochemicals, as exemplified by research with soy isoflavones (Andlauer et al., 2000). 

The metabolism and bioavailability of isoflavonoids is likely to be of crucial importance to their ability to help protect human health against disease. Many studies have been published on the metabolism and bioavailability of isoflavones in adults. The metabolism of isoflavones is of particular interest because the potency of isoflavone metabolites differs from that of the parent compounds. The daidzein metabolite equol is three times as potent as is daidzein in an endometrial tumor line. Equol is also a more potent antioxidant in vitro (see Sections 7.3.5 and 7.4.2) ° and the clinical significance of the ability to form equol has been considered in depth. ... 

Isoflavonoids are metabolically derived from the flavanones. The central step is the migration from the C2 to the C3 of the aryl block, which constitutes the B ring of the flavanone intermediate. This reaction is catalysed by 2-hydroxyflavone synthase, a cytochrome P450. At the same time, the isoflavones are precursors of a substantial number of compounds involved in the biosynthesis of phytoalexins and pterocarpanes. 

Isoflavones, a special kind of polyphenols, show similar behaviour regarding absorption and metabolism to this family of compounds. Thus, Scalbert et al [12] put forward two primary sources of evidence concerning the absorption of polyphenols first, indirect evidence for their absorption through the gut barrier as can be seen from the increase in the antioxidant capacity of the plasma following the consumption of polyphenol-rich foods, and second, their recovery in urine after the ingestion of given amounts of a particular polyphenol. 

Since polyphenols are retained until they, or their metabolic products, are excreted by the urine or faeces, they undergo a number of complex microbial and chemical transformations that may include chemical conjugation, hydrolysis and biliary excretion [12], The few existing studies in humans show that the quantities of polyphenols found intact in urine vary from one phenolic compound to another. Among flavonoids, recovery is low for some flavonols, such as quercetin and rutin (0.3-14%), but high for other flavonoids, such as catechins, anthocyanins, flavanones and soy isoflavones (3-27%) [13],... 

Regarding the formation of these isoflavone derivatives, it is extremely interesting that some people are unable to produce equol or that they produce it in very low amounts. In fact, studies report that a third part of the general population cannot form equol. This demonstrates that the breakdown of isoflavones by the microflora in the gut determines the recovery of the compounds, and that the excretion to the urine of equol and other isoflavones derivatives, such as O-DMA, is dependent on the different composition of intestinal microflora. To confuse the issue even more, some researchers report that the production of isoflavone derivatives, such as equol, also depends on diet and gender a high fat/meat content diet increases equol production in women but not in men, which is explained by promotion of the growth or the activity of the bacterial populations responsible for equol production. On the other hand, no age-related differences for isoflavone metabolism have been reported [12, 13],... 

The basic structural model of flavanones is the 2-phenylbenzopiran-4-one skeleton [6], The flavanones are compounds of great interest due to the fact that they are a compulsory step in the metabolic pathway of the other flavonoids. Their metabolic precursors are the chalcones, and the flavones, the dihydroflavonols, and the isoflavones are biosynthesised from the flavanones. 

Common nutritional compounds, such as omega-3 fatty acids and isoflavones have been shown to alter genes that code for cytokines, growth factors, cholesterol metabolizing enzymes, and fipoproteins. " ... 

In that context, the present chapter gives insights into the relevance of phenolic compounds in human nutrition. We will primarily discuss bioavailability and biological properties of isoflavones and lignans in the context of human health and disease, our main focus being the metabolic activities of intestinal bacteria. 

Fig. 78.1 Phenolics in human nutrition A microbiological perspective. Bioavailability of dietary compounds depends on the sum of molecular mechanisms underlying liberation of the compounds from dietary matrices, absorption, distribution into body tissues via blood circulation, metabolism (in the GI tract or target tissues), and elimination from the body. The keypad shows parameters of relevance to phenolic bioavailability. The two enlarged windows illustrate the diversity of both phenolics in food and microbial functions involved in phenolic conversion, with a focus on isoflavones and hgnans. Estimates of blood concentration of daidzein, equol, and enterolignans are...

However, there are exceptions, such as the isoflavone irilone, which seems to be resistant to bacterial conversion [85]. Gut bacteria catalyze an array of dominant core reactions that play key roles in the metabolism of a large panel of phenolic compounds, including isoflavones and lignans (I) hydrolysis of esterified and conjugated bounds, (II) deglycosylation (removal of sugar moieties),... 

One of the main reasons for this lack of concretion is the complexity of plant matrices, whose diversified secondary metabolism includes a vast number of different compounds with close structures that can be hard to identify. Some of these families with a well-documented bibliography related to health effects comprise alkaloids, phenolic compounds (including phenolic acids, stilbenes like resveratrol, or flavonoids such as anthocyanins, procyanidins, or isoflavones), terpenoids, carotenoids, sulfur compounds (such as glucosinolates and isothiocyanates), etc. Their presence and amount in the plant source depend on multiple factors including variety, organ of the plant, soil, sun exposure, climate, or even ways of cultivation. 

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