WBM ↔ microbiome drug metabolism
The whole-body models (Harvey/Harvetta) metabolise drugs and conjugate the products — chiefly by glucuronidation (host UGT reactions consuming UDP-glucuronate). Gut microbes in AGORA2/APOLLO carry the reverse reaction, β-glucuronidase (_GLCAASE), releasing the aglycone and free glucuronate — the enterohepatic recycling loop. This page links the two: which WBM drug-glucuronides a microbe already de-conjugates, and which are easy expansion targets for the microbial reconstructions.
Descriptive analysis over a public knowledge base. Candidates are curation suggestions for human review — no reconstruction is modified here. Not clinical, diagnostic, or individual guidance.
The enterohepatic loop, mechanistically
What a candidate expansion adds: a single β-glucuronidase hydrolysis, built only from metabolites that already exist in the database.
aglycone + udpglcur → glucuronide + udpglucuronide + h2o → aglycone + glcur — the reaction a candidate is missingWhy glucuronidation
The drug conjugation systems in the reconstruction, and whether AGORA2/APOLLO has a reverse enzyme that genuinely de-conjugates each (a microbial reaction that releases the free conjugating group — transport of the intact conjugate does not count). β-glucuronidase is broadly distributed; the sulfate / acetyl / glutathione reverse enzymes are absent — so glucuronidation is the only class where an expansion is both needed and templateable.
| Conjugation | Donor | Microbial reverse enzyme | Drug conjugates | Microbially de-conjugated | Templateable? |
|---|---|---|---|---|---|
| Glucuronidation | udpglcur | β-glucuronidase _GLCAASE | 924 | 157 | yes |
| Sulfation | paps | arylsulfatase sulfatase | 229 | 0 | no enzyme |
| Acetylation | accoa | deacetylase / esterase | 106 | 0 | no enzyme |
| Glutathione conjugation | gthrd | γ-glutamyl / mercapturate | 70 | 0 | no enzyme |
Drug glucuronides ↔ microbial β-glucuronidase
Sources: host drug metabolism reconws_drug_reaction (model 255659) → reconws_smatrix / wbm_reaction (Harvey/Harvetta); microbial β-glucuronidase from reactions (isMicrobe=1, _GLCAASE) → recon → reconstructions (AGORA2/APOLLO). A glucuronide is a non-cofactor product of a drug reaction consuming udpglcur; its aglycone is the conjugated substrate a microbe would release. A candidate is host-produced but consumed by no microbial β-glucuronidase — the (propose) reaction is a curation suggestion (hover for the full formula), not an applied change.