bilirubin conjugation

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of bilirubin monoglucuronide or bilirubin diglucuronide, water-soluble derivatives of bilirubin. [DOI:10.1016/0305-0491(80)90243-6]

Bilirubin conjugation is a crucial process in the detoxification of bilirubin, a yellow pigment produced during the breakdown of heme, the iron-containing molecule found in red blood cells. The process involves a two-step enzymatic transformation of bilirubin into a water-soluble form, allowing it to be excreted in bile.

Here's a detailed breakdown:

1. **Unconjugated bilirubin:**
- Unconjugated bilirubin is produced in the spleen, liver, and bone marrow during the breakdown of heme.
- It is highly hydrophobic (water-insoluble) and toxic to the nervous system, particularly in newborns.
- It circulates in the bloodstream bound to albumin, a protein that makes it more soluble.

2. **Step 1: Glucuronidation:**
- In the liver, unconjugated bilirubin undergoes glucuronidation by the enzyme UDP-glucuronosyltransferase (UGT).
- UGT catalyzes the transfer of glucuronic acid from UDP-glucuronic acid to bilirubin, forming bilirubin monoglucuronide and then bilirubin diglucuronide.
- This conjugation process adds polar groups to bilirubin, making it more hydrophilic (water-soluble).

3. **Step 2: Bile excretion:**
- The conjugated bilirubin, now water-soluble, is secreted into the bile.
- Bile, a fluid produced by the liver, is transported to the gallbladder for storage and then released into the small intestine during digestion.
- In the intestine, conjugated bilirubin is further metabolized by bacteria, leading to the formation of urobilinogen, which is mainly excreted in the feces, giving the stool its brown color.
- A small amount of urobilinogen is reabsorbed into the bloodstream and excreted in urine, giving urine its characteristic yellow color.

4. **Clinical significance:**
- Impaired bilirubin conjugation, often due to genetic deficiencies in UGT, can lead to hyperbilirubinemia, a condition where bilirubin levels in the blood are elevated.
- This can manifest as jaundice, a yellow discoloration of the skin and eyes.
- In newborns, hyperbilirubinemia can be particularly serious, potentially leading to kernicterus, a neurological disorder that can cause brain damage.
- Other factors, such as liver disease, infections, and certain medications, can also affect bilirubin conjugation.
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Proteins (4)

Compounds (73)