Bile acid profiles in peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.

Abstract

Fast atom bombardment mass spectrometry and gas chromatography-mass spectrometry were used to analyze bile acids in the body fluids of an infant (L.C.) whose liver contained no immunoreactive peroxisomal 3-oxoacyl-CoA thiolase. The profiles were compared with those of six patients with undetectable peroxisomes (Zellweger syndrome) and two siblings (N.B. and I.B.) whose defect of peroxisomal fl-oxidation could not be localized by morphological studies of peroxisomes or by immunoblotting of peroxisomal fl-oxidation proteins.

Identification of intermediates in the bile acid synthetic pathway as ligands for the farnesoid X receptor

“…However, much higher levels of these C 27 bile acids are present in the plasma of patients with inherited peroxisome disorders, such as Zellweger syndrome, than the levels of CA and CDCA in normal subjects (37,38), and the concentration of 25-OH-THC [10] in the hepatic microsomes of CTX patients is 20-to 100-fold higher than in control subjects (39). Our findings indicate that these precursors modulate FXR target gene expression more potently or TABLE 1.…”

Aberrant Oxidation of the Cholesterol Side Chain in Bile Acid Synthesis of Sterol Carrier Protein-2/Sterol Carrier Protein-x Knockout Mice

“…Model analyses have shown that 27-NC-24-one is formed readily via spontaneous decarboxylation from 3␣,7␣,12␣-trihydroxy-24-keto-cholestanoic acid (22), which comes from the expected biosynthetic cholic acid intermediate 3␣,7␣,12␣-trihydroxy-24-keto-cholestanoyl-CoA. 27-NC-24-one has been found in an earlier study besides varanic acid and 3␣,7␣,12␣-trihydroxy-⌬24-cholestenoic acid in a human patient who may have had thiolase deficiency (36). Thus, we think that our results show convincingly that side chain oxidation is inhibited in vivo in SCP2/SCPx knockout mice at the thiolytic step that takes place in peroxisomal ␤-oxidation of THCA-CoA.…”

Familial Giant Cell Hepatitis with Low Bile Acid Concentrations and Increased Urinary Excretion of Specific Bile Alcohols: A New Inborn Error of Bile Acid Synthesis?

“…Materials used for analysis of plasma bile acids by GC-MS (11)(12)(13)(14) and for analysis of urinary cholanoids by FAB-MS (3,14,15) have been described previously. For analysis of urinary bile alcohols by GC-MS, P-glucuronidase/sulfatase from Helix pomatia was obtained from Sigma Chemical Co. Ltd. (Poole, Dorset, UK).…”

“…The dried eluate was reconstituted in toluene/hexane (1:1, vol/vol) and subjected to chromatography on neutral alumina (as used in the purification of bile acid methyl esters). The TMS ethers of the bile alcohols were prepared and analyzed by GC-MS using the same gas chromatography and mass spectrometry settings as used for bile acids (13,14). Urinary bile alcohol profiles from the patient described below were compared with profiles from normal infants, from infants with cholcstatic liver disease of known cause and from three adults with CTX (samples supplied by Dr. B. J. Koopman).…”

“…injection of cholecystokinin. The bile was analyzed by FAB-MS and by GC-MS after enzymatic deconjugation (14). Quantitation of bile acid concentrations was achieved by the use of nordeoxycholic acid as internal standard (as for plasma samples).…”