Cuarto Ideosema : La masculinidad hegemónica

Lithocholic acid (3a-hydroxy-5 p-cholanoic acid) and 3 p-hydroxy-5-cholenoic acid are the major monohydroxy bile acids. They are found in the bile, blood and urine of normal subjects and patients with liver disease as sulphate esters or glucuronides of their amino-acid conjugates. 3 p-hydroxy-5-cholenoic acid is one of the major bile acids found in the meconium of newborn infants (Back, 1973). The 3 P-hydroxy epimer, the 7p-hydroxy isomer and the a//o-isomer of lithocholic acid have also been reported. Two C27 monohydroxy bile acids, 3a-hydroxy-5P-cholestan-26-oic acid and 3 P-hydroxy-5P-cholesten-26-oic acid have been found in children with coprostanic acidaemia (Janssen et al. 1982). The latter bile acid has also been demonstrated in the blood of both healthy adults and patients with other liver diseases (Axelson et al.

1988).

2.3.2. Dihydroxy bile acids

The three major bile acids in humans are the dihydroxy derivatives of 5P- cholanoic acid, chenodeoxycholic acid (3 a, 7a-dihydroxy-5 P-cholanoic acid), ursodeoxycholic acid (3a,7p-dihydroxy-5P-cholanoic acid) and deoxycholic acid (3a, 12a-dihydroxy-5p-cholanoic acid). Chenodeoxycholic is a primary bile acid, ie. it is synthesised in the liver. The other dihydroxy bile acids are secondary (bacterially modified, eg. deoxycholic acid) or tertiary (have bacterial and hepatic modification, eg. ursodeoxycholic acid).

Dihydroxy bile acids in bile are almost exclusively conjugated with glycine or taurine, whereas, in urine, they are excreted in large part as double conjugates eg.

glycochenodeoxycholic acid-3-sulphate; however, each bile acid has a different conjugate profile. Chenodeoxycholic acid and deoxycholic acid appear as sulphates, glucuronides and glucosides. Ursodeoxycholic acid, on the other hand, is the only bile acid to undergo 7V-acetylglucosaminidation. Hyodeoxycholic acid is extensively converted to its 6a-glucuronide.

Various isomers of these bile acids have been discovered with improved isolation techniques and analytical procedures. The C27 analogues (5P-cholestan-26- oic acids) of chenodeoxycholic acid and deoxycholic acid were first identified in alligators before their detection in humans (Tint et al. 1981). Several unsaturated dihydroxy bile acids have been reported, namely 3a,7a-dihydroxy-, 3p,7a-dihydroxy- and 3a, 12a-dihydroxy-5-cholenoic acids (Bremmelgaard, 1979). These bile acids are found in the blood of healthy subjects. They are excreted in the urine in large part as their sulphate esters, which is an important compensation for children with a deficiency of 3p-hydroxysteroid dehydrogenase A^^'^-isomerase (Clayton, 1991).

2.3.3. Trihydroxy bile acids

Four common bile acids with trivial names in the 5P-cholanoic acid series have three hydroxyl groups, hyocholic acid (3a,6a,7a-trihydroxy-5P-cholanoic acid), a - muricholic acid (3a,6p,7a-trihydroxy-5p-cholanoic acid), P-muricholic acid (3a,6P,7P-trihydroxy-5P-cholanoic acid), and cholic acid (3a,7a,12a-trihydroxy-5P- cholanoic acid). Hyocholic acid is the principal bile acid of the pig, a - and p- muricholic acids are found in rats, and cholic acid is a primary bile acid in many species, including humans. Hyocholic acid is found in man in patients with cholestasis and in newborn infants, but not healthy adults (Summerfield et al. 1976).

Trihydroxy bile acids are mostly found as their glycine and taurine conjugates in bile, blood and urine. Sulphate, glucuronide, and glucoside conjugates are found in urine, but in lesser amounts than the corresponding conjugates of the mono or dihydroxy bile acids. Many other isomers of the 3, 6, 7- and 3, 7, 12-trihydroxy series exist. Ursocholic acid (3a,7p,12a-trihydroxy-SP-cholanoic acid) is present in most patients with cholestasis and in the urine of healthy adults of all ages (Summerfield et al. 1977).o-Muricholic acid (3a,6a,7p-trihydroxy-5P-cholanoic acid) is also found in small amounts in the urine of healthy adults and in patients with primary biliary cirrhosis (Batta et al. 1989; Nakashima et al. 1986). The unsaturated bile acid, 3a,7a,12a-trihydroxy-5p-cholenoic acid, was found in the urine of young twins with intrahepatic cholestasis (Clayton et al. 1987). The C27 analogue of cholic acid, 3a,7a,12a-trihydroxy-5p-cholestan-26-oic acid, is a major bile acid of the alligator and is also found in children with certain cholestatic syndromes (Eyssen et al. 1972; Hanson a/. 1975; Mathis 1980).

2.3.4. Tetrahydroxy bile acids

Tetrahydroxy bile acids have mostly been reported in patients with cholestasis. As they are highly polar molecules, they are excreted into the urine in the unconjugated form and only very small amounts appear in the bile. Hydroxylation of cholic acid at positions 1, 6 and 23 have been reported (Bremmelgaard, 1979; Thomassen, 1979). Tetrahydroxy bile acids, such as ip,3a,7a,12a-tetrahydroxy-5P- cholan-24-oic acid, have been shown to be the major components in the urine in the neonatal period (Kimura et al. 1994).

2.3.5. Oxo bile acids

Oxo bile acids are believed to originate from the action of bacteria on the hydroxy bile acids. It has been suggested that the altered redox state of the neonatal liver could account for the accumulation of unsaturated oxo bile acids, such as 7a, 12a-dihydroxy-3- 0 X 0 - 5 P-chol-l-enoic acid, in the urine of newborns (Wahlen et al.

1989). Another unsaturated oxo bile acid is 7a-hydroxy-3-oxo-4-cholestenoic acid, which is found in the blood of healthy subjects and those with liver diseases.

Since the oxo bile acids which are absorbed from the intestine are mostly reduced to their hydroxy forms before excretion into bile, in liver diseases where there is reduced liver function, accumulation of oxo bile acids should be anticipated. Increased urinary excretion of 3-oxo-A"* bile acids has been reported by Kimura et al in Japanese patients with idiopathic neonatal hepatitis (Kimura et al. 1998; Kimura et al.

1998).

2.3.6. Conjugation with amino acids

Substantial variation of the ratio of glycine- and taurine-conjugated bile acids occurs both between species, and between normal and cholestatic states. In the rat, taurine conjugates are found almost exclusively in bile, whereas in man, glycine conjugates predominate (Sjovall, 1960). Cholestasis increases the proportion of taurine conjugates in man (Carey, 1969). In contrast in intestinal disease, which leads to the malabsorption of bile acids, there is an increase in the proportion of glycine conjugates. This is due to the limiting availability of taurine in the hepatocyte in humans (Linstedt et al. 1965). Since in man, taurine cannot be synthesised from other sulphur-containing amino acids, the immediate dietary intake of taurine and its distribution govern the rate of formation of taurine bile acid conjugates.

2.4. Bile acid profiles in infancy and childhood