Conversion of 3α,7α,12α-trihydroxy-5β-cholestanoic acid into cholic acid by rat liver peroxisomes

Abstract

3a,7ar,l2o-Trihydroxy-SP-cholestanoic acid (THCA) is considered to be a precursor for cholic acid formation [l]. 3a,7a,l2cr,24-Tetrahydroxy-5/3cholestanoic acid is a probable intermediate in the reaction [2-4]. 24-Hydroxylation of THCA has been shown to be catalyzed by the mitochondrial fraction of rat liver in combination with the 100 000 X g supematant fluid [4,5]. The microsomal fraction in combination with the 100 000 X g supernatant and ATP also catalyzes 24hydroxylation [4] and the reaction was shown to be due to the combined action of a desaturase and a hydratase [4]. The final thiolytic cleavage of the side chain in cholic acid formation [6] has been shown to be catalyzed by the mitochondrial fraction [3 5 ;I], the soluble fraction [3,5], or by a combination of the microsomal fraction and the 100 000 X g supernatant [7]. The over-all formation of cholic acid from THCA in the mitochondrial fraction is dependent on the presence of ATP, coenzyme A, NAD and Mg2+ in the reaction medium [5 ;I]. It thus appears that this reaction has certain features in common with the Poxidation of fatty acids. Recently, a fatty acid oxidizing system different from the one present in the mitochondria has been identified in the peroxisomal fraction of both rat [8,9] and human [lo] liver. On the basis of these findings the subcellular localization of cholic acid formation has been further investigated. This work shows that the peroxisomal fraction of rat liver is able to catalyze the conversion of THCA into cholic acid.