Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia.
Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression.
Department of Pharmaceutics, School of Pharmacy, Kitasato University, Tokyo, Japan. Electronic address: fujiwarar@pharm.kitasato-u.ac.jp.
Ryoichi
R
Fujiwara
Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan.
Yoshihiro
Y
Maruo
Department of Pharmacology, Laboratory of Environmental Toxicology, University of California at San Diego, La Jolla, CA 92093, USA.
Shujuan
S
Chen
Department of Pharmacology, Laboratory of Environmental Toxicology, University of California at San Diego, La Jolla, CA 92093, USA; Department of Chemistry & Biochemistry, Laboratory of Environmental Toxicology, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address: rtukey@ucsd.edu.
Robert H
RH
Tukey
D001663:Bilirubin / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007567:Jaundice, Neonatal / Q000235:genetics / Q000473:pathology*; D008099:Liver / Q000378:metabolism; D008895:Milk, Human / Q000737:chemistry*; D011110:Polymorphism, Genetic; D000099148:UGT1A1 Enzyme
D001663:Bilirubin; D020719:Glucuronides; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme
Bilirubin; Extra hepatic; Gilbert's Syndrome; Humanized UGT1 Mice; UDP-glucuronosyltransferase 1A1