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PW-052 Xenobiotic & Drug Metabolism Biotransformation unreviewed

Phase II - Conjugation

Phase I metabolite or parent drug Water-soluble conjugate (glucuronide, sulfate, GSH, acetyl, methyl)
Compartment
Cytosol + ER
Main tissue
Liver mainly
Rate-limiting
Not flagged in the source
Steps
5

Reaction steps

In source order, 5 total

showing 1–5
  1. 1

    Substrate + UDP-glucuronate -> glucuronide + UDP

    UDP-glucuronosyltransferase (UGT) 2.4.1.17 ST-0370 Irreversible/directional UDP-glucuronic acid
    In UDP-glucuronate
    Out Glucuronide UDP
    › Notes

    Quantitatively the most important conjugation; the pathway that clears bilirubin (UGT1A1) and many drugs.

  2. 2

    Substrate + PAPS -> sulfate conjugate + PAP

    Sulfotransferase (SULT) 2.8.2.- ST-0371 Irreversible/directional PAPS
    In PAPS
    Out PAP
    › Notes

    High-affinity but low-capacity; saturates before glucuronidation.

  3. 3

    Electrophile + GSH -> GS-conjugate -> mercapturic acid

    Glutathione S-transferase (GST) 2.5.1.18 ST-0372 Irreversible/directional Glutathione
    In Glutathione (GSH)
    Out GS-conjugate
    › Notes

    Detoxifies reactive intermediates such as NAPQI from paracetamol.

  4. 4

    Substrate + acetyl-CoA -> acetylated metabolite + CoA-SH

    N-acetyltransferase (NAT1/NAT2) 2.3.1.5 ST-0373 Irreversible/directional Acetyl-CoA
    In Acetyl-CoA
    Out Acetylated metabolite CoA-SH
    › Notes

    NAT2 slow-acetylator status predisposes to isoniazid neuropathy and hydralazine-induced lupus.

  5. 5

    Substrate + SAM -> methylated metabolite + SAH

    COMT / TPMT / methyltransferases 2.1.1.6 / 2.1.1.67 ST-0374 Irreversible/directional SAM
    In S-adenosylmethionine (SAM)
    Out S-adenosylhomocysteine
    › Notes

    TPMT deficiency causes severe myelosuppression with azathioprine and 6-mercaptopurine.

Showing all 5 steps.

Recent literature

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Europe PMC · fetched just now · sorted by publication date

  1. 1
    Antiepileptic drug therapy in companion animals: New perspectives on clinical pathology monitoring.

    Lotfalizadeh N, Nazifi S. · 2026-07-29

    open access unreviewed
  2. 2
    Mechanistic pathways linking gut microbial metabolites, microbial structural products, and host-microbe co-metabolites to mitochondrial function.

    Frye RE, Rossignol DA. · 2026-08-06

    open access unreviewed
  3. 3
    Comparative Pharmacokinetics of Six Bioactive Constituents From Danggui Jixueteng Decoction in Normal and Myelosuppressive Rats.

    Guo M, Liu Y, Hu Z, Liu X. · 2026-07-01

    open access unreviewed
  4. 4
    Rarely reported cases of hepatotoxicity associated with turmeric- and curcuminoid-containing dietary supplements: a comprehensive review by USP.

    Akhtar N, Barnes J, Gardiner P, Gurley BJ, Ko R, Koturbash I, Patel D, van Breemen RB, Roe AL. · 2026-06-27

    cited 1× open access unreviewed
  5. 5
    Significance of GSH and H<sub>2</sub>S regulation for cancer: an intricate interplay between diet, microbiota, metabolic reprogramming, and immune health.

    Majumder A, Majumder S, Bano S, Sen K, Nayak KB. · 2026-06-11

    open access unreviewed
  6. 6
    First-trimester preeclampsia prediction model via integrative machine learning of maternal risk profiles and laboratory markers.

    Zhu Y, Zhang Y, Huang C, Zhang S, Cao J, Miranda N, Zhao S, Peng Y, Yu C, Feng B, Jin J, Tang Q, Fan J, Qiao … · 2026-02-09

    cited 1× open access unreviewed
  7. 7
    Polyphenol‐Rich Foods as a Healthy and Sustainable Strategy: Mental Health and Metabolomic Profiling

    Gómez Nieto M, Puertas‐Martín V, Chamorro S, Méndez‐Guerrero A, Álvarez‐Acero I, Balderas C, de Pascual‐Teres… · 2026-10-07

    open access unreviewed
  8. 8
    Quercetin as a modulator of xenobiotic metabolism: integrating CYP450 regulation, phase II conjugation pathways, and transporter-mediated drug interactions.

    Sulaiman SH, Omer RA, Muhammad HY, Qadir AM, Barzani HAH. · 2026-10-03

    unreviewed
  9. 9
    Bile acid signaling in health and disease.

    Fan Z, He M, Liang T, Zhang B, Zhao N, Li P. · 2026-10-02

    open access unreviewed
  10. 10
    Concurrent Antidepressant Use and Metastasis Risk Among Women Receiving Tamoxifen for Breast Cancer: A Real-World Cohort Study.

    Elshafie S, Zuber M, Gomez-Lumbreras A, Malone DC, Villa Zapata L. · 2026-10-01

    open access unreviewed

External claims. These come from an index outside this database and are not checked against it. Treat them as leads.