Familial Hypercholanemia (FHCA)


Familial Hypercholanemia can be caused by mutations in the TJP2, BAAT or EPHX1 genes which code for bile acid-CoA:amino acid N-acyltransferase, which is involved in bile acid metabolism. In liver hepatocytes, it catalyzes the second step in the conjugation of C24 bile acids (choloneates) to glycine and taurine before excretion into bile canaliculi. The major components of bile are cholic acid and chenodeoxycholic acid. In a first step the bile acids are converted to an acyl-CoA thioester, either in peroxisomes (primary bile acids deriving from the cholesterol pathway), or cytoplasmic at the endoplasmic reticulum (secondary bile acids). May catalyze the conjugation of primary or secondary bile acids, or both. The conjugation increases the detergent properties of bile acids in the intestine, which facilitates lipid and fat-soluble vitamin absorption. In turn, bile acids are deconjugated by bacteria in the intestine and are recycled back to the liver for reconjugation (secondary bile acids). Bile acid-CoA:amino acid N-acyltransferase may also act as an acyl-CoA thioesterase that regulates intracellular levels of free fatty acids. Familial hypercholanemia is characterized by increased bile acids in plasma. Symptoms include rickets and steatorrhea.

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References

  1. OMIM: Entry 607748
  2. Uniprot: Q14032
  3. Carlton VE, Harris BZ, Puffenberger EG, Batta AK, Knisely AS, Robinson DL, Strauss KA, Shneider BL, Lim WA, Salen G, Morton DH, Bull LN: Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. Nat Genet. 2003 May;34(1):91-6. Pubmed
  4. Zhu QS, Xing W, Qian B, von Dippe P, Shneider BL, Fox VL, Levy D: Inhibition of human m-epoxide hydrolase gene expression in a case of hypercholanemia. Biochim Biophys Acta. 2003 Jul 30;1638(3):208-16. Pubmed