Peroxisomal bile acid-CoA:amino-acid N-acyltransferase in rat liver.
Bile acid-CoA:amino-acid N-acyltransferase activity was measured in subcellular fractions of rat liver homogenate. The conversion of [14C]choloyl-CoA and [14C]chenodeoxycholoyl-CoA into the corresponding [14C]tauro- and glyco-bile acids was calculated after isolation of the product by high performance liquid chromatography. There was an enrichment of bile acid-CoA:amino-acid N-acyltransferase activity in the light mitochondrial (L) fraction and to a lesser extent in the microsomal fraction. Surprisingly, no enrichment was found in the cytosolic fraction. Subfractionation of the L-fraction by Nycodenz gradient centrifugation, showed that the activity of the N-acyltransferase had a bimodal distribution and co-sedimented with peroxisomes (particulate catalase) and microsomes (esterase). The highest specific amidation activity of both choloyl-CoA and chenodeoxycholoyl-CoA was always found in the most peroxisome-rich fractions. [14C]Taurocholate formation in the peroxisomal fraction was 2.2 mumol/mg of protein/min. Striking differences were observed in the Km values and the saturation concentrations for glycine and taurine. The peroxisomal amidation of [14C]choloyl-CoA had a Km for taurine of 0.9 x 10(-3) M and for glycine of 17 x 10(-3) M. The results are consistent with the possibility that most of de novo synthesized bile acids conjugate to taurine by a peroxisomal bile acid-taurine N-acyltransferase in rat liver. The bile acids deconjugated in the gut and recirculating to the liver may be activated and amidated by the microsomal enzyme system prior to biliary secretion.
Kase
B F
BF
Department of Paediatric Research, Rikshospitalet, Oslo, Norway.
Björkhem
I
I
D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism; D006000:Glycocholic Acid / Q000378:metabolism; D007472:Iohexol; D008099:Liver / Q000201:enzymology*; D008297:Male; D008830:Microbodies / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000201:enzymology; D013654:Taurine / Q000378:metabolism; D013656:Taurocholic Acid / Q000378:metabolism
D001647:Bile Acids and Salts; D013654:Taurine; D007472:Iohexol; D013656:Taurocholic Acid; D000217:Acyltransferases; C025118:cholyl CoA glycine-taurine N-acyltransferase; D006000:Glycocholic Acid; D005998:Glycine