Cholyl coenzyme

The oxidation of the side chain of 5j -cholestane-3a,7a,12a-triol to yield cholic acid or rather cholyl coenzyme A entails an co-oxidation followed by a jS-oxidation (Fig. 2). Early investigations (71,72) showed that the mitochondrial fraction of rat and mouse liver homogenate catalyzed the conversion of 5jS-cholestane-3a,7a, 12a-triol into 5/5-cholestane-3a,7a, 12a,26-tetrol and, when supplemented with the 100,000g supernatant fluid, the further transformation of 5j -cholestane-3a,7a,12a,26-tetrol into 3a,7a,12a-trihydroxy-5/9-cholestanoic acid (Fig. 2). Suld et al. (72) showed that the conversion of 3a,7a,12a-trihydroxy-5/5-cholestanoic acid into cholic acid (cholyl coenzyme A), catalyzed by the mitochondrial fraction fortified with the 100,000g supernatant fluid, occurs with the release of propionic acid (propionyl coenzyme A). 

Fig. 2. Conversion of 5/ -cholestane-3a,7a,12a-triol into cholyl coenzyme A. IX, 5)5-Cholestane-3a,7a,12a-triol X, 5 -cholestane-3a,7a,12a,26-tetrol XI, 3a,7a,12a-trihydroxy-5/5-cholestanoic acid XII, 3a,7a,12a-trihydroxy-5i3-choles-tanoyl coenzyme A XIII, 3a,7a,12a,24a-tetrahydroxy-5/5-cholestanoyl coenzyme A XIV, propionyl coenzyme A XV, cholyl coenzyme A.

Let us review some of the conventions used, when talking about enzyme-catalyzed reactioixs. The first reaction depicted in Figure 2.7 involves three substrates (cholate, HS-CoA, and ATF) and three products (cholyl-S-CoA, AMFJ and PPi). The substrates are shown on the left-hand side of the arrows, while the products are shown on the right-hand side, ATP is used to drive the reaction, i.e., to make it occur in the direction of the arrow. Since consumption of ATP is not the goal of this particular reaction, ATP may be called a co-subslrale. The abbreviation HS-CoA mearts coenzyme A. Cholate is the ionized forru of cholic acid-... 

In the taurocholic acid synthesizing system of rat liver microsomes, the fact that the soluble cytoplasmic fraction could be substituted for, by CoA and ATP, appeared to indicate the existence of cholyl-CoA as an activated intermediate (12). This was independently observed by a number of investigators (13-17). In Bremer s studies (13), the conjugation of cholic acid with taurine by rat liver microsomes at pH 7.3-7.6 required coenzyme A, ATP, Mg2+, Mn +, and fluoride to inhibit ATPase activity. In some cases, cysteine and glutathione stimulated the activity. In this report, a reaction mechanism involving cholyl-S-CoA as an intermediate and AMP and pyrophosphate as reaction products was proposed, in which the transfer of the cholyl group from CoA to taurine and glycine is irreversible. Since hepatic microsomes... 

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See also in sourсe #XX -- [ ]

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