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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
    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
  2. 2
    Cylindrospermopsin toxicokinetics: in silico ADMET modeling, rat and human liver microsome metabolism, and UHPLC-MS/MS metabolite characterization.

    Cascajosa-Lira A, Guzmán-Guillén R, Cameán AM, Jos A, Prieto AI. · 2026-04-28

    unreviewed
  3. 3
    Genome assembly of Elcysma westwoodi provides insights into host-plant cyanogenic glucoside detoxification and chemical defence gene evolution.

    Choi M, Khan M, Kim J. · 2026-06-28

    unreviewed
  4. 4
    Bioassay-Guided Phytochemical Investigation of Vietnamese <i>Vitex rotundifolia</i> Leaves and the Liverwort <i>Ptychanthus striatus</i> as Sources of SARS-CoV-2 Main Protease Inhibitors.

    Nguyen HT, Tran TD, Duong TH, Bui TH, Pham NK, Pham MD, Phan HT, Mai DT, Pathummanee W, Pham DD, Jamnongkan T. · 2026-06-08

    open access unreviewed
  5. 5
    The In Vivo Existence Forms of Engeletin and Their Anti-Hyperuricemia Activity

    Lv Y, Zhang J, Chen S, Zhang J, Han X, Shang M, Liu G, Wang X, Cai S, Xu F. · 2026-06-01

    open access unreviewed
  6. 6
    Sambucus ebulus L. Fruits: Phytochemistry, Molecular Mechanisms, and Biological Activities in Inflammation, Infection, and Cancer

    Barbolov M, Stoyanov S, Radeva M, Boshnakov P, Yaneva G, Ivanova D, Tasinov O. · 2026-06-01

    open access unreviewed
  7. 7
    Astragalus and Cordyceps Derivatives in the Treatment of Aging-Related Chronic Diseases and Neurodegenerative Disorders

    Kanubaddi K, Yaung C, Harn H, Chiou T, Hsu S, Wijaya I, Lin S, Wuli W. · 2026-06-01

    open access unreviewed
  8. 8
    Flavonoids as Nutraceuticals to Treat Inflammatory Diseases: Focusing on Quercetin, Kaempferol, Luteolin, Apigenin, Epicatechin and Their Effects on Hepatic, Nervous, and Pulmonary Systems

    Piva M, Martelossi-Cebinelli G, Mendes-Pierotti S, Chinen W, Cardines P, Martinez R, Georgetti S, Baracat M, … · 2026-06-01

    open access unreviewed
  9. 9
    Research Progress on the Treatment of Renal Injury with Esculetin: Multi-Target Pharmacological Mechanism and Clinical Translation Prospect

    Zhou R, Chen J, Xia B, Chen M, Zhu Y, Li G. · 2026-06-01

    open access unreviewed
  10. 10
    Molecular, Microbial, and Ecological Drivers of Duckweed Phytoremediation in Aquatic Environments.

    Thingujam D, Malacrinò A, Pajerowska-Mukhtar KM, Mukhtar MS, Mukhtar MS. · 2026-06-19

    open access unreviewed

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