Deconjugation is a biochemical reaction, primarily occurring in the enterohepatic circulation, where a previously conjugated, or inactivated, molecule is cleaved back into its active or unconjugated form. This process is often mediated by bacterial enzymes, particularly beta-glucuronidase, in the gut. In the context of hormonal health, it critically influences the reabsorption and subsequent systemic recirculation of metabolized hormones, notably estrogens, thereby increasing the effective circulating load.
Origin
The term is derived from the chemical process of ‘conjugation,’ which involves attaching a water-soluble molecule like glucuronic acid or sulfate to a lipophilic compound for easier excretion. Deconjugation is the reverse reaction, first observed and studied in the context of xenobiotic and steroid hormone metabolism and clearance pathways. It highlights a critical, often overlooked, regulatory point in endocrine homeostasis, particularly involving the gut-liver axis.
Mechanism
During Phase II liver detoxification, hormones are conjugated to render them inactive and ready for biliary excretion into the intestine. However, certain gut bacteria possess deconjugating enzymes that hydrolyze the conjugate bond, releasing the active, unconjugated hormone. This free hormone can then be passively reabsorbed across the intestinal wall back into the bloodstream, increasing the systemic hormone load and potentially contributing to conditions like estrogen dominance or other hormonal imbalances.
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