Conjugates - considered to be polar molecules that can be readily excreted by the body and are often

inactive

Most of the reactions do this except for glycine and glutamine since the substrate is initially activated.

Glucuronidation reaction

Most common reaction in adults: Glucuronidation

Most common reaction in children: Sulfation

Formation of the β-glucuronides involves two steps: synthesis of the activated coenzyme which is
uridine-5’diphospho-α-D-glucuronic acid (UDPGA) and the subsequent transfer of the glucuronyl group
from UDPGA to the substrate. Synthesis of UDPGA utilizes α-D-glucose-1-phosphate as its initial
precursor (Wilson et al., 2011).

Unconjugated bilirubin may go to the blood brain barrier and may cause kernicterus encephalopathy

Phenolic and alcoholic hydroxyls are the most common functional groups undergoing glucuronidation in
drug metabolism

Sulfate conjugation
Missing enzyme: APs phosphokinase

However, O-sulfate conjugates of some N-hydroxy compounds give rise to chemically reactive
intermediates that are toxic. Phenacetin, an analgesic, is metabolized into N-hydroxyphenacetin and
subsequently conjugated with sulfate. The O-sulfate conjugate of N-hydroxyphenacetin can bind
covalently to microsomal proteins which can lead to reactive intermediates responsible for
hepatotoxicity and nephrotoxicity of the discontinued drug

Amino Acid Conjugation

Phenylacetic acid derivatives: Diclofenac, Ketorolac

GSH or Mercapturic Acid Conjugation

GSH can protect cells against chemically reactive species due to its nucleophilic SH group

Azathioprine- immunosuppressant; prodrug of 6-mercaptopurine; can be used for rheumatoid arthritis

and immunosuppresion

Methylation
Common endogenous compounds: epinephrine and melatonin
Inactivation of biologic amines: NE, Dopamine, Serotonin, and Histamine
Methionine: presence of thioether