Bile acid crosstalk with sulfur amino acid metabolism. (IMAGE)
Caption
Liver is the major organ for metabolism of sulfur amino acids (methionine, cysteine, taurine) and expresses high levels of sulfur amino acid synthesis and metabolising enzymes. Dietary intake, methionine (via transsulfuration pathway) and autophagy-mediated protein breakdown are major sources of cellular cysteine. Cysteine is the substrate for synthesis of the antioxidant glutathione (GSH). Cysteine conversion to taurine is a major cysteine elimination pathway and this process is catalysed by cysteine dioxygenase 1 (CDO1) and cysteine sulfinic acid decarboxylase (CSAD). Taurine is used in hepatocytes for bile acid conjugation. Bile acids activate farnesoid X receptor (FXR) to repress the expression of CDO1 and CSAD to inhibit taurine synthesis and at the same time repress cholesterol 7⍺-hydroxylase (CYP7A1) to inhibit bile acid synthesis. Therefore, FXR coordinates the synthesis of taurine with bile acids synthesis. FXR repression of cysteine catabolism helps preserve cellular cysteine availability for synthesis of GSH, which plays a key role in regulating cellular redox homeostasis and antioxidant defence against cellular oxidative stress.
Credit
By Tiangang Li, Mohammad Nazmul Hasan, Lijie Gu.
Usage Restrictions
Credit must be given to the creator. Only noncommercial uses of the work are permitted.
License
CC BY-NC