The functional heterogeneity of
uridine diphosphate-
glucuronosyltransferase (UDPGT) and its deficiency in human liver were investigated. The
monoclonal antibody (MAb) WP1, which inhibits
bilirubin and
phenol-glucuronidating activity, was used to immunopurify UDPGTs from human liver. Purified UDPGTs were injected into mice to obtain new MAbs. Immunoblotting of microsomes with MAb HEB7 revealed at least three
polypeptides in liver (56, 54, and 53 kD) and one in kidney (54 kD). In liver microsomes from four patients (A, B, C, and D) with
Crigler-Najjar syndrome type I (CN type I), UDPGT activity towards
bilirubin was undetectable (A, B, C, and D) and activity towards phenolic compounds and
5-hydroxytryptamine either reduced (A and B) or normal (C and D). UDPGT activity toward
steroids was normal. Immunoblot studies revealed that the
monoclonal antibody WP1 recognized two
polypeptides (56 and 54 kD) in liver microsomes from patient A and none in patient B. With HEB7 no immunoreactive
polypeptides were seen in these two patients. Patient C showed a normal banding pattern and in patient D only the 53-kD band showed decreased intensity. These findings suggest considerable heterogeneity with regard to the expression of UDPGT
isoenzymes among CN type I patients.