5. Glucuronidation is catalyzed by UDP-glucuronosyltransferases (UGTs) which belongs to a super family of endoplasmic reticulum membrane bound enzymes residing on the luminal surface of the endoplasmic reticulum. The UGT activity is highest in liver, kidney and intestine (activity depends on factors like age, gender, hormonal status, genetic factors and environmental exposures). Two large families of UGT, sharing more than 50% amino acid identity, UGT1 and UGT2 exist.

In humans UGT1 exist as 9 isozymes (UGT1A1, UGT1A3-UGT1A10) and in rats it exists as 7 isozymes (UGT1A1-UGT1A3, UGT1A5-UGT1A8). The UGT1 family members contain identical carboxyl terminal sequence since they share four exons located at the 3' end of the UGT1 locus. At the 5'end of the common exons a series of first exons encoding for the complete amino terminal sequence of the UGT1 family are positioned. The amino terminal codons are unique for each member of the UGT1 family. The naming of UGT1 genes is based on the relative position of the first exon with the common exon. The first exon of UGT1A1 is closest to the common exon whereas first exon of UGT1A10 is the farthest from the common exon. Each overlapping gene in the UGT1 gene complex has a unique promoter which enables the gene to independently regulate its activity in tissues in response to different inducing stimuli.

The UGT2 family is encoded by independent genes. In humans UGT2 exist in six forms (UGT2B4, UGT2B7, UGT2B10, UGT2B11, UGT2B15 and UGT2B17). In rats it exists in seven forms (UGT2A1, UGT2B1, UGT2B2, UGT2B3, UGT2B6, UGT2B8, and UGT2B12). In human the UGT2 isoforms are encoded by a cluster of genes present on the chromosome 4.

The UGT1A1 is involved in the glucuronidation of bilirubin whereas all others are involved in the glucuronidation of xenobiotics and other endotoxic substances. The full length cDNA of the gene UGT1A1 has been successfully cloned and sequenced.

6. After successful conjugation the conjugated bilirubin is secreted into the bile and then into the intestine.

7. In the intestine the glucuronic acid is removed by the bacteria and the bilirubin is converted to urobilinogen. Some amount of urobilinogen is reabsorbed from the intestine and enters the hepatic portal blood.

8. A part of this urobilinogen participates in the enterohepatic urobilinogen cycle whereas the remaining urobilinogen is transported to the kidneys where it is converted to urobilin that imparts yellow color to the urine. In the large intestine and colon the urobilinogen is oxidized by the bacteria to brown stercobilin that imparts the characteristic color to the feces.