|
|
Am J Hum Genet. 1997 November; 61(5): 1153–1162. | PMCID: PMC1716023 |
D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder. Y Suzuki, L L Jiang, M Souri, S Miyazawa, S Fukuda, Z Zhang, M Une, N Shimozawa, N Kondo, T Orii, and T Hashimoto Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan. ysuz@cc.gifu-u.ac.jp Abstract Peroxisomal beta-oxidation proceeds from enoyl-CoA through D-3-hydroxyacyl-CoA to 3-ketoacyl-CoA by the D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxy-acyl-CoA dehydrogenase bifunctional protein (d-bifunctional protein), and the oxidation of bile-acid precursors also has been suggested as being catalyzed by the d-bifunctional protein. Because of the important roles of this protein, we reinvestigated two Japanese patients previously diagnosed as having enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (L-bifunctional protein) deficiency, in complementation studies. We found that both the protein and the enzyme activity of the d-bifunctional protein were hardly detectable in these patients but that the active L-bifunctional protein was present. The mRNA level in patient 1 was very low, and, for patient 2, mRNA was of a smaller size. Sequencing analysis of the cDNA revealed a 52-bp deletion in patient 1 and a 237-bp deletion in patient 2. This seems to be the first report of D-bifunctional protein deficiency. Patients previously diagnosed as cases of L-bifunctional protein deficiency probably should be reexamined for a possible d-bifunctional protein 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 (2.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. Images in this article Click on the image to see a larger version. These references are in PubMed. This may not be the complete list of references from this article. - Adamski J, Normand T, Leenders F, Monté D, Begue A, Stéhelin D, Jungblut PW, de Launoit Y. Molecular cloning of a novel widely expressed human 80 kDa 17 beta-hydroxysteroid dehydrogenase IV. Biochem J. 1995 Oct 15;311(Pt 2):437–443. [PubMed]
- Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [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]
- Furuta S, Miyazawa S, Osumi T, Hashimoto T, Ui N. Properties of mitochondria and peroxisomal enoyl-CoA hydratases from rat liver. J Biochem. 1980 Oct;88(4):1059–1070. [PubMed]
- Hashimoto T. Individual peroxisomal beta-oxidation enzymes. Ann N Y Acad Sci. 1982;386:5–12. [PubMed]
- Nakajima-Iijima S, Hamada H, Reddy P, Kakunaga T. Molecular structure of the human cytoplasmic beta-actin gene: interspecies homology of sequences in the introns. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6133–6137. [PubMed]
- Jiang LL, Kobayashi A, Matsuura H, Fukushima H, Hashimoto T. Purification and properties of human D-3-hydroxyacyl-CoA dehydratase: medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase. J Biochem. 1996 Sep;120(3):624–632. [PubMed]
- Jiang LL, Kurosawa T, Sato M, Suzuki Y, Hashimoto T. Physiological role of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein. J Biochem. 1997 Mar;121(3):506–513. [PubMed]
- Jiang LL, Miyazawa S, Hashimoto T. Purification and properties of rat D-3-hydroxyacyl-CoA dehydratase: D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein. J Biochem. 1996 Sep;120(3):633–641. [PubMed]
- Jiang LL, Miyazawa S, Souri M, Hashimoto T. Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein. J Biochem. 1997 Feb;121(2):364–369. [PubMed]
- Kobayashi A, Jiang LL, Hashimoto T. Two mitochondrial 3-hydroxyacyl-CoA dehydrogenases in bovine liver. J Biochem. 1996 Apr;119(4):775–782. [PubMed]
- Kunau WH, Dommes V, Schulz H. beta-oxidation of fatty acids in mitochondria, peroxisomes, and bacteria: a century of continued progress. Prog Lipid Res. 1995;34(4):267–342. [PubMed]
- Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
- LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
- Markwell MA, Haas SM, Bieber LL, Tolbert NE. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem. 1978 Jun 15;87(1):206–210. [PubMed]
- Miyazawa S, Osumi T, Hashimoto T. The presence of a new 3-oxoacyl-CoA thiolase in rat liver peroxisomes. Eur J Biochem. 1980 Feb;103(3):589–596. [PubMed]
- Nakada Y, Hyakuna N, Suzuki Y, Shimozawa N, Takaesu E, Ikema R, Hirayama K. A case of pseudo-Zellweger syndrome with a possible bifunctional enzyme deficiency but detectable enzyme protein. Comparison of two cases of Zellweger syndrome. Brain Dev. 1993 Nov–Dec;15(6):453–456. [PubMed]
- Natowicz MR, Evans JE, Kelley RI, Moser AB, Watkins PA, Moser HW. Urinary bile acids and peroxisomal bifunctional enzyme deficiency. Am J Med Genet. 1996 May 17;63(2):356–362. [PubMed]
- Osumi T, Hashimoto T, Ui N. Purification and properties of acyl-CoA oxidase from rat liver. J Biochem. 1980 Jun;87(6):1735–1746. [PubMed]
- Pedersen JI. Peroxisomal oxidation of the steroid side chain in bile acid formation. Biochimie. 1993;75(3-4):159–165. [PubMed]
- Poll-The BT, Roels F, Ogier H, Scotto J, Vamecq J, Schutgens RB, Wanders RJ, van Roermund CW, van Wijland MJ, Schram AW, et al. A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodystrophy). Am J Hum Genet. 1988 Mar;42(3):422–434. [PubMed]
- Reddy JK, Mannaerts GP. Peroxisomal lipid metabolism. Annu Rev Nutr. 1994;14:343–370. [PubMed]
- Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [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]
- Singh H, Usher S, Johnson D, Poulos A. A comparative study of straight chain and branched chain fatty acid oxidation in skin fibroblasts from patients with peroxisomal disorders. J Lipid Res. 1990 Feb;31(2):217–225. [PubMed]
- Suzuki Y, Shimozawa N, Yajima S, Tomatsu S, Kondo N, Nakada Y, Akaboshi S, Lai M, Tanabe Y, Hashimoto T, et al. Novel subtype of peroxisomal acyl-CoA oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein: identification by means of complementation analysis. Am J Hum Genet. 1994 Jan;54(1):36–43. [PubMed]
- Suzuki Y, Shimozawa N, Yajima S, Yamaguchi S, Orii T, Hashimoto T. Effects of sodium 2-[5-(4-chlorophenyl)pentyl]-oxirane-2-carboxylate (POCA) on fatty acid oxidation in fibroblasts from patients with peroxisomal diseases. Biochem Pharmacol. 1991 Feb 1;41(3):453–456. [PubMed]
- ten Brink HJ, Poll-The BT, Saudubray JM, Wanders RJ, Jakobs C. Pristanic acid does not accumulate in peroxisomal acyl-CoA oxidase deficiency: evidence for a distinct peroxisomal pristanyl-CoA oxidase. J Inherit Metab Dis. 1991;14(5):681–684. [PubMed]
- ten Brink HJ, Wanders RJ, Stellaard F, Schutgens RB, Jakobs C. Pristanic acid and phytanic acid in plasma from patients with a single peroxisomal enzyme deficiency. J Inherit Metab Dis. 1991;14(3):345–348. [PubMed]
- Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PubMed]
- Van Veldhoven PP, Huang S, Eyssen HJ, Mannaerts GP. The deficient degradation of synthetic 2- and 3-methyl-branched fatty acids in fibroblasts from patients with peroxisomal disorders. J Inherit Metab Dis. 1993;16(2):381–391. [PubMed]
- Wanders RJ, van Roermund CW, Brul S, Schutgens RB, Tager JM. Bifunctional enzyme deficiency: identification of a new type of peroxisomal disorder in a patient with an impairment in peroxisomal beta-oxidation of unknown aetiology by means of complementation analysis. J Inherit Metab Dis. 1992;15(3):385–388. [PubMed]
- Wanders RJ, van Roermund CW, Schelen A, Schutgens RB, Tager JM, Stephenson JB, Clayton PT. A bifunctional protein with deficient enzymic activity: identification of a new peroxisomal disorder using novel methods to measure the peroxisomal beta-oxidation enzyme activities. J Inherit Metab Dis. 1990;13(3):375–379. [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]
- Watkins PA, McGuinness MC, Raymond GV, Hicks BA, Sisk JM, Moser AB, Moser HW. Distinction between peroxisomal bifunctional enzyme and acyl-CoA oxidase deficiencies. Ann Neurol. 1995 Sep;38(3):472–477. [PubMed]
- Yamaguchi S, Orii T, Sakura N, Miyazawa S, Hashimoto T. Defect in biosynthesis of mitochondrial acetoacetyl-coenzyme A thiolase in cultured fibroblasts from a boy with 3-ketothiolase deficiency. J Clin Invest. 1988 Mar;81(3):813–817. [PubMed]
|
This article has been 
