The bile acid composition of gastric contents from neonates with high intestinal obstruction

Abstract

The study was designed to identify 'atypical' bile acids in gastric contents from three neonates with high intestinal obstruction on the basis that this was likely to represent a rich source of primary bile acids. Cholic acid was the major component, and related 'atypical' bile acids included its C-3 and C-7 oxidation products, its 3 beta-epimer and 2 beta- and 6 alpha-hydroxylation products. Allocholic acid was the only 5 alpha-cholanic acid derivative identified. 7 alpha, 12 alpha-Dihydroxy-3-oxochol-4-en-24-oic acid was found in all three specimens and might be an intermediate in a biosynthetic pathway from cholesterol to cholic acid in which side-chain oxidation precedes at least some of the nuclear changes. Side-chain-hydroxylated derivatives of trihydroxycoprostanic acid were also detected and these may represent intermediates in biosynthetic pathways from cholesterol to cholic acid via 5 beta-cholestan-3 alpha, 7 alpha, 12 alpha-triol. The most abundant bile acid of this type was (25 epsilon)-3 alpha, 7 alpha, 12 alpha, 25-tetrahydroxy-5 beta-cholestan-26-oic acid, which suggested that C-25 hydroxylation may be an important step in the shortening of the C8 side chain of the cholestane triol to the C5 side chain of cholic acid in the neonatal period. Bile acids lacking a substituent at C-12 included chenodeoxycholic acid, its C-3 and C-7 oxidation products, its 3 beta-epimer and its 6 alpha-hydroxylation product (hyocholic acid).

Biliary Bile Acid Composition of the Human Fetus in Early Gestation

“…The ions at mlz 548,458, 368, and 253 are characteristic of a trihydroxy-50-cholanoic structure and the significant ion at mlz 369 suggests that two of the hydroxyls are on adjacent carbons (3 1, 32). The significant and prominent ion at mlz 18 1 may arise from a disubstituted A or B ring structure, but the spectra is not typical of I-hydroxylated structures, all of which exhibit a diagnostically significant ion at mlz 217, nor is it similar to reported spectra of 26-hydroxy bile acids (7,32). Bile acids with 3,6,7-trihydroxy structures have characteristic ions at mlz 195 and 285, not seen in this mass spectrum.…”

“…Bile acids with 3,6,7-trihydroxy structures have characteristic ions at mlz 195 and 285, not seen in this mass spectrum. An unidentified bile acid with the same series of ions was found in the gastric aspirate from newborn infants (7,8). This mass spectra does not match any of the 98 spectra of bile acids recently compiled (32) and further work is required to elucidate the structure of this quantitatively important compound.…”

Defective peroxisomal cleavage of the C27-steroid side chain in the cerebro-hepato-renal syndrome of Zellweger.

“…3). The value of 20% found after 35 h was based on very low activity (-200 dpm for tritium) and might therefore be uncertain. Fig.…”

Delta 4-3-oxosteroid 5 beta-reductase deficiency described in identical twins with neonatal hepatitis. A new inborn error in bile acid synthesis.

“…Hydroxylations at positions C-7 of the steroid nucleus, and C-12 for cholic acid, and oxidation of the side chain are also required. Studies of human fetal gallbladder bile indicate that while bile acid synthesis is relatively well developed in early gestation (2,3), alternative pathways in metabolism are operative during human development, including additional hydroxylations of the steroid nucleus (3)(4)(5)(6)(7)(8)(9).…”

“…4--P-14-, (2) allo-cholic; (3) chenodeoxycholic; (4) trihydroxy bile acid possibly 3f,7a, 12a-trihydroxy-5a-cholanoic; (5) hyocholic; (6) 7a-hydroxy-3-oxo-4-cholenoic; (7) 7a, 12a-dihydroxy-3-oxo-4-cholenoic; internal standard-coprostanol. Bile acids identified in the chromatograms of healthy infant urine are denoted by letters and identifications listed in Table II Figure 3.…”