Drug Metabolism & Transporters

Phase II Metabolism

TRFaz II Metabolizma
Also known as:Phase 2 metabolism · Conjugation reactions

Conjugation reactions in which an endogenous moiety such as glucuronic acid, sulfate, glutathione, an acetyl or a methyl group is attached to a drug or to its phase I metabolite.

In depth

The main pathways are glucuronidation (UGTs), sulfation (sulfotransferases), acetylation (N-acetyltransferases), methylation (e.g. TPMT, COMT), glutathione conjugation (glutathione S-transferases) and amino acid conjugation. Most require an activated cofactor, such as UDP-glucuronic acid, PAPS or acetyl-CoA, and a suitable functional group on the substrate.

Conjugation usually yields water-soluble, inactive products excreted in urine or bile, but acetylation and methylation can reduce water solubility, and some conjugates are active (morphine-6-glucuronide) or reactive (acyl glucuronides). Polymorphisms in NAT2, TPMT and UGT1A1 have well-established clinical consequences.

Clinical pearl

NAT2 slow acetylators have higher isoniazid exposure and a greater risk of peripheral neuropathy and hepatotoxicity; reduced UGT1A1 function (e.g. *28 homozygotes) increases irinotecan (SN-38) toxicity.

Example drugs

Lorazepam Morphine Isoniazid Irinotecan
TRIn Turkish

Faz II Metabolizma

Bir ilaca veya onun faz I metabolitine glukuronik asit, sülfat, glutatyon, asetil ya da metil grubu gibi endojen bir grubun bağlandığı konjugasyon tepkimeleridir.

Başlıca yollar glukuronidasyon (UGT'ler), sülfasyon (sülfotransferazlar), asetilasyon (N-asetiltransferazlar), metilasyon (ör. TPMT, COMT), glutatyon konjugasyonu (glutatyon S-transferazlar) ve amino asit konjugasyonudur. Çoğu, UDP-glukuronik asit, PAPS veya asetil-KoA gibi aktive edilmiş bir kofaktöre ve substratta uygun bir fonksiyonel gruba gereksinim duyar.

Konjugasyon genellikle idrar veya safra ile atılan, suda çözünür ve inaktif ürünler oluşturur; ancak asetilasyon ve metilasyon suda çözünürlüğü azaltabilir ve bazı konjugatlar aktif (morfin-6-glukuronid) ya da reaktif (açil glukuronidler) olabilir. NAT2, TPMT ve UGT1A1 polimorfizmlerinin klinik sonuçları iyi tanımlanmıştır.

NAT2 yavaş asetilatörlerinde izoniazid maruziyeti daha yüksek, periferik nöropati ve hepatotoksisite riski daha fazladır; UGT1A1 işlevi azalmış kişilerde (ör. *28 homozigotlar) irinotekan (SN-38) toksisitesi artar.

Diğer adları:Faz 2 reaksiyonları · Konjugasyon reaksiyonları
Updated 24.09.2026 1 views Educational reference — verify against current sources before clinical use.

Read next

Phase I MetabolismFaz I Metabolizma

Functionalization reactions, mainly oxidation, reduction and hydrolysis, that introduce or unmask a polar group such as –OH, –NH2 or –COOH on a drug molecule.

 GlucuronidationGlukuronidasyon

A phase II conjugation reaction in which UDP-glucuronosyltransferases (UGTs) transfer glucuronic acid from UDP-glucuronic acid to a hydroxyl, carboxyl, amine or thiol group on a drug or metabolite.

 Slow AcetylatorYavaş Asetilatör

A phenotype defined by reduced N-acetyltransferase 2 (NAT2) activity, causing slower inactivation of drugs cleared by acetylation and greater exposure at standard doses.

 TPMT and NUDT15TPMT ve NUDT15

Two enzymes whose genetic deficiency reduces inactivation of thiopurine drugs, causing excess active metabolite accumulation and a markedly increased risk of severe myelosuppression.

 Drug Metabolismİlaç Metabolizması

The enzymatic biotransformation of drugs and other xenobiotics into metabolites that are usually more polar and more readily excreted, occurring mainly in the liver.

 Active MetaboliteAktif Metabolit

A product of drug metabolism that has pharmacological activity of its own, which may be similar to, greater than or different from that of the parent drug.