# Soy Isoflavones and PCOS: Role in Hormonal and Metabolic Mechanisms
## 3 Biochemistry of Soy Isoflavones
### Daidzein and Equol  
Daidzein (7-hydroxy-3-(4-hydroxyphenyl))chrom-4-one) is, alongside genistein, one of the principal representatives of isoflaves [61]. It occurs predominantly in leguminous plants, with soy and soy-based products--such as miso, tempeh, tofu, soy flour, soy yogurt, soy drink, and sufu--being the richest dietary sources. This compound is also present in other plants, including common beans, mung beans, fava beans, red clover, broccoli, and asparagus, as well as in nuts and seeds [62]. Similar to genistein, daidzein's lipophilicity and extensive intestinal-hepatic metabolism result in its low bioavailability--approximately 6% [63; 64]. Like other isoflaves, it cannot be absorbed in the human intestine in its conjugated form; it must first undergo hydrolysis into its active aglycone form via \(\beta\)-glucuronidase in the small intestine [65]. The resulting aglycone can be directly absorbed and transported to the liver, where it is conjugated by hepatic enzymes to form sulphated, glycosylated, and glucuronidated isoflaves [66]. Alternatively, it may undergo further metabolic transformations mediated by the gut microbiota, including hydroxylation, demethylation, methylation, reduction, or C-ring cleavage [67]. These transformations can lead to the formation of secondary metabolites such as equol, dihydroadzein, and O-desmethylangolenin [68; 69]. Equol, also known as (3S)-3-(4-hydroxyphenyl)-3,4-dihydro-2H-chromen-7-ol, is the most metabolically active derivative of daidzein and exhibits higher biological activity than both daidzein and genistein [70]. Studies indicate that only a subset of the population possesses the ability to synthesize equol microbiologically. It is estimated that approximately 80-90% of individuals produce O-desmethylangolensin--a compound devoid of hormonal activity--whereas only 25-50% of the population can convert daidzein into equol via intestinal bacteria [71; 72; 73]. The highest prevalence of equol producers is observed  
Figure 2: Skeletal structures of selected soy isoflaves (genistein, daidzein, and equol) and oestradiol. among Asian populations, suggesting a significant influence of environmental factors, including dietary patterns [74]. Notably, one study found that 59% of vegetarians were equal producers, compared to only 29% among meat-eaters, implying that dietary composition may substantially affect the gut microbiota's capacity to metabolise daidzein [72]. Bacteria responsible for equal production primarily belong to the family _Coriobacteriaceae_, including species such as _Adlerceurtzia equolfaciens_, _Asaccharobacter celatus_, _Enterorhabolus mucosicola_, _Slackia isoflavoniconvertens_, and _Slackia equolfaciens_. Additionally, certain strains from the genera _Lactobacillus_, _Lactococcus_, and _Bifidobacterium_ have also demonstrated the ability to produce equql [67]. Both daidzein and equql bind to ER\(\alpha\) and ER\(\beta\), with a greater affinity for the ER\(\beta\) isoform. Equol displays a higher affinity for oestrogen receptors than its precursor daidzein, reaching a level comparable to that of genistein [75]. Due to the unequal expression of ER\(\alpha\) and ER\(\beta\) in different tissues, the effect of equql may vary and depend on the local ratio of receptor isoforms. ER\(\alpha\) is primarily expressed in the uterus, and to a lesser extent in the ovaries, intestines, and skin. In contrast, ER\(\beta\) expression is found in the ovaries, colon, kidneys, central nervous system (CNS), and cardiovascular system [76]. In addition, the effect of equql as an agonist or antagonist may be modulated by the concentration of endogenous oestrogens, which have a higher affinity for both receptor types [67]. Both daidzein and equql exhibit a range of therapeutic properties, including the ability to neutralize reactive oxygen species and prevent oxidative stress, primarily through the activation of antioxidant enzymes [77].