Phase II - Conjugation

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.