Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Direct hyperbilirubinemia, may result from a variety of pathologies, including structural obstructions with biliary tract occlusions (as in cholelithiasis), infections (e.g. hepatitis) and genetic disorders (Rotor's and Dubin-Johnson's syndrome). One of the less common and probably more frequently underdiagnosed causes is benign recurrent intrahepatic cholestasis (BRIC). First described in 1959, BRIC was further classified into two subgroups which differ in their pathogenesis and clinical manifestation. Both BRIC types originate from impaired function bile salt excretion from hepatocytes to the canaliculi which is mediated by the bile salt export pump (BSEP) which is located on the hepatyocyte membrane, unevenly distributed within the membrane lipid bilayer. In BRIC type-I, a mutation impairs the asymmetrical distribution of BSEP. In BRIC type-II, a mutation occurs directly damaging the BSEP. Apart from cholestasis, clinical manifestations of BRIC type-I include extra-hepatic symptoms such as watery diarrhea, pancreatitis and hearing impairment. Patients with BRIC type-II present mainly with hepatobiliary disease such as colelithiasis. In the past, BRIC was conventionally considered to result in no more than canalicular cholestasis, however several reports have associated BRIC with fibrosis and porto-portal septa formation. Disease course may last between weeks and months, more common in females, at any age, and usually resolves spontaneously, although chronic liver disease has also been described. Treatment modalities range from expectant management, medication (cholestyramine, ursolit) or even surgery (biliary bypass/liver transplantation). This report describes a patient with BRIC type-II and reviews the relevant literature.
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PMID:[Benign recurrent intrahepatic cholestasis type-II--a rare cause of direct hyperbilirubinemia exacerbations with hepatic fibrosis]. 1877 Sep 56

Phosphatidylethanolamine N-methyltransferase (PEMT) is a hepatic integral membrane protein localized to the endoplasmic reticulum (ER). PEMT catalyzes approximately 30% of hepatic phosphatidylcholine (PC) biosynthesis. Pemt-/- mice fed a high-fat diet (HFD) develop steatohepatitis. Interestingly, portions of the ER located close to the canaliculus are enriched in PEMT. Phospholipid balance and asymmetrical distribution by adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1) on the canalicular membrane is required for membrane integrity and biliary processes. We hypothesized that PEMT is an important supplier of PC to the canaliculus and that PEMT activity is critical for the maintenance of canalicular membrane integrity and bile formation following HFD feeding when there is an increase in overall hepatic PC demand. Pemt+/+ and Pemt-/- mice were fed a chow diet, an HFD, or a choline-supplemented HFD. Plasma and hepatic indices of liver function and parameters of bile formation were determined. Pemt-/- mice developed cholestasis, i.e, elevated plasma bile acid (BA) concentrations and decreased biliary secretion rates of BAs and PC, during HFD feeding. The maximal BA secretory rate was reduced more than 70% in HFD-fed Pemt-/- mice. Hepatic ABCB11/bile salt export protein, responsible for BA secretion, was decreased in Pemt-/- mice and appeared to be retained intracellularly. Canalicular membranes of HFD-fed Pemt-/- mice contained fewer invaginations and displayed a smaller surface area than Pemt+/+ mice. Choline supplementation (CS) prevented and reversed the development of HFD-induced cholestasis. Conclusion: We propose that hepatic PC availability is critical for bile formation. Dietary CS might be a potential noninvasive therapy for a specific subset of patients with cholestasis.
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PMID:Impaired Hepatic Phosphatidylcholine Synthesis Leads to Cholestasis in Mice Challenged With a High-Fat Diet. 3076 63