|
|
J Clin Invest. 1990 April; 85(4): 1267–1273. doi: 10.1172/JCI114563. | PMCID: PMC296562 |
Bile acid profiles in peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. P T Clayton, E Patel, A M Lawson, R A Carruthers, and J Collins Department of Child Health, Institute of Child Health, London, United Kingdom. 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 beta-oxidation could not be localized by morphological studies of peroxisomes or by immunoblotting of peroxisomal beta-oxidation proteins. 3 alpha, 7 alpha, 12 alpha-Trihydroxy-5 beta-cholestan-26-oic acid (THCA) was present in bile and plasma of all patients. However, bile from L.C., N.B. and I.B. contained unconjugated varanic acid (3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestan-26-oic acid) as the major C27 bile acid, whereas bile from Zellweger patients contained only small amounts of varanic acid. In the bile from L.C. two isomers of varanic acid were present; in the bile from N.B. and I.B. a single isomer predominated. L.C., N.B., and I.B. all produced bile containing small amounts of (24E)-3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-en-26-oic acid [( 24E]-delta 24-THCA), its [24Z]- isomer, 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-23-en-26-oic acid and 3 alpha, 7 alpha, 12 alpha-trihydroxy-27-nor-5 beta-cholestan-24-one. The results provide evidence for peroxisomal pathways for cholic acid synthesis in man via THCA, delta 24-THCA and varanic acid and show that bile acid analyses can be used to diagnose peroxisomal thiolase deficiency. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. These references are in PubMed. This may not be the complete list of references from this article. - Kase F, Björkhem I, Pedersen JI. Formation of cholic acid from 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid by rat liver peroxisomes. J Lipid Res. 1983 Dec;24(12):1560–1567. [PubMed]
- Miura S, Mori M, Takiguchi M, Tatibana M, Furuta S, Miyazawa S, Hashimoto T. Biosynthesis and intracellular transport of enzymes of peroxisomal beta-oxidation. J Biol Chem. 1984 May 25;259(10):6397–6402. [PubMed]
- Tager JM, Van der Beek WA, Wanders RJ, Hashimoto T, Heymans HS, Van den Bosch H, Schutgens RB, Schram AW. Peroxisomal beta-oxidation enzyme proteins in the Zellweger syndrome. Biochem Biophys Res Commun. 1985 Feb 15;126(3):1269–1275. [PubMed]
- Swell L, Gustafsson J, Danielsson H, Schwartz CC, Vlahcevic ZR. Biosynthesis of bile acids in man. An in vivo evaluation of the conversion of R and S 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic and 3 alpha, 7 alpha, 12 alpha-24 xi-tetrahydroxy-5 beta-cholestanoic acids to cholic acid. J Biol Chem. 1981 Jan 25;256(2):912–916. [PubMed]
- Moser HW. The peroxisome: nervous system role of a previously underrated organelle. The 1987 Robert Wartenberg lecture. Neurology. 1988 Oct;38(10):1617–1627. [PubMed]
- Kase BF, Björkhem I, Hågå P, Pedersen JI. Defective peroxisomal cleavage of the C27-steroid side chain in the cerebro-hepato-renal syndrome of Zellweger. J Clin Invest. 1985 Feb;75(2):427–435. [PubMed]
- Goldfischer S, Collins J, Rapin I, Neumann P, Neglia W, Spiro AJ, Ishii T, Roels F, Vamecq J, Van Hoof F. Pseudo-Zellweger syndrome: deficiencies in several peroxisomal oxidative activities. J Pediatr. 1986 Jan;108(1):25–32. [PubMed]
- Schram AW, Goldfischer S, van Roermund CW, Brouwer-Kelder EM, Collins J, Hashimoto T, Heymans HS, van den Bosch H, Schutgens RB, Tager JM, et al. Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2494–2496. [PubMed]
- Clayton PT, Lake BD, Hjelm M, Stephenson JB, Besley GT, Wanders RJ, Schram AW, Tager JM, Schutgens RB, Lawson AM. Bile acid analyses in "pseudo-Zellweger" syndrome; clues to the defect in peroxisomal beta-oxidation. J Inherit Metab Dis. 1988;11(Suppl 2):165–168. [PubMed]
- Lawson AM, Madigan MJ, Shortland D, Clayton PT. Rapid diagnosis of Zellweger syndrome and infantile Refsum's disease by fast atom bombardment--mass spectrometry of urine bile salts. Clin Chim Acta. 1986 Dec 15;161(2):221–231. [PubMed]
- Clayton PT, Lake BD, Hall NA, Shortland DB, Carruthers RA, Lawson AM. Plasma bile acids in patients with peroxisomal dysfunction syndromes: analysis by capillary gas chromatography-mass spectrometry. Eur J Pediatr. 1987 Mar;146(2):166–173. [PubMed]
- Setchell KD, Worthington J. A rapid method for the quantitative extraction of bile acids and their conjugates from serum using commercially available reverse-phase octadecylsilane bonded silica cartridges. Clin Chim Acta. 1982 Oct 27;125(2):135–144. [PubMed]
- Clayton PT, Muller DP. A simplified gas-liquid chromatographic methods for the estimation of non-sulphated plasma bile acids. Clin Chim Acta. 1980 Aug 19;105(3):401–405. [PubMed]
- Clayton PT, Muller DP, Lawson AM. The bile acid composition of gastric contents from neonates with high intestinal obstruction. Biochem J. 1982 Sep 15;206(3):489–498. [PubMed]
- Setchell KD, Lawson AM, Tanida N, Sjövall J. General methods for the analysis of metabolic profiles of bile acids and related compounds in feces. J Lipid Res. 1983 Aug;24(8):1085–1100. [PubMed]
- Setchell KD, Matsui A. Serum bile acid analysis. Clin Chim Acta. 1983 Jan 7;127(1):1–17. [PubMed]
- Norman A, Strandvik B. Formation and metabolism of bile acids in extrahepatic biliary atresia. J Lab Clin Med. 1971 Aug;78(2):181–193. [PubMed]
- Une M, Nagai F, Kihira K, Kuramoto T, Hoshita T. Synthesis of four diastereoisomers at carbons 24 and 25 of 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestan-26-oic acid, intermediates of bile acid biosynthesis. J Lipid Res. 1983 Jul;24(7):924–929. [PubMed]
- Ali SS, Stephenson E, Elliott WH. Bile acids. LXVII. The major bile acids of Varanus monitor. J Lipid Res. 1982 Sep;23(7):947–954. [PubMed]
- Une M, Kuramoto T, Hoshita T. The minor bile acids of the toad, Bufo vulgaris formosus. J Lipid Res. 1983 Nov;24(11):1468–1474. [PubMed]
- Une M, Nagai F, Hoshita T. High-performance liquid chromatographic separation of higher bile acids. J Chromatogr. 1983 Mar 4;257(2):411–415. [PubMed]
- Noma Y, Une M, Kihira K, Yasuda M, Kuramoto T, Hoshita T. Bile acids and bile alcohols of bullfrog. J Lipid Res. 1980 Mar;21(3):339–346. [PubMed]
- Une M, Morigami I, Kihira K, Hoshita T. Stereospecific formation of (24E)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-en-26-oic acid and (24R,25S)-3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestan-26-oic acid from either (25R)- or (25S)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid by rat liver homogenate. J Biochem. 1984 Oct;96(4):1103–1107. [PubMed]
- Chu CH, Schulz H. 3-Hydroxyacyl-CoA epimerase is a peroxisomal enzyme and therefore not involved in mitochondrial fatty acid oxidation. FEBS Lett. 1985 Jun 3;185(1):129–134. [PubMed]
- Kärki T, Hakkola E, Hassinen IE, Hiltunen JK. Beta-oxidation of polyunsaturated fatty acids in peroxisomes. Subcellular distribution of delta 3,delta 2-enoyl-CoA isomerase activity in rat liver. FEBS Lett. 1987 May 11;215(2):228–232. [PubMed]
- Karlaganis G, Karlaganis V, Sjövall J. Identification of 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24 xi, 25 xi,26-hexol and partial characterization of the bile alcohol profile in urine. J Lipid Res. 1984 Jul;25(7):693–702. [PubMed]
- Watkins PA, Chen WW, Harris CJ, Hoefler G, Hoefler S, Blake DC, Jr, Balfe A, Kelley RI, Moser AB, Beard ME, et al. Peroxisomal bifunctional enzyme deficiency. J Clin Invest. 1989 Mar;83(3):771–777. [PubMed]
|
This article has been