HSD17B4

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Species	Human	Mouse
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D-bifunctional protein (DBP), also known as peroxisomal multifunctional enzyme type 2 (MFP-2), as well as 17β-hydroxysteroid dehydrogenase type IV (17β-HSD type IV) is a protein that in humans is encoded by the HSD17B4 gene. It's an alcohol oxidoreductase, specifically 17β-Hydroxysteroid dehydrogenase. It is involved in fatty acid β-oxidation and steroid metabolism (cf. steroidogenesis).

Function

The HSD17B4 gene encodes an enzyme involved in peroxisomal fatty acid beta-oxidation. It was first identified as a 17-beta-estradiol dehydrogenase (Leenders et al., 1996; van Grunsven et al., 1998). Peroxisomal beta-oxidation of fatty acids, originally described by Lazarow and de Duve (1976), is catalyzed by 3 enzymes: acyl-CoA oxidase (see, e.g., ACOX1, MIM 609751); the 'D-bifunctional enzyme,' with enoyl-CoA hydratase and D-3-hydroxyacyl-CoA dehydrogenase activity, and 3-ketoacyl-CoA thiolase (MIM 604054).

See also the L-bifunctional peroxisomal protein (EHHADH; MIM 607037). The D- and L-bifunctional proteins have different substrate specificities. The D-bifunctional protein catalyzes the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids and also acts in shortening cholesterol for bile acid formation. In contrast, the L-specific bifunctional protein does not have the latter 2 activities (Jiang et al., 1997).[supplied by OMIM]

See also

• D-bifunctional protein deficiency
• Perrault syndrome

Further reading

• de Launoit Y, Adamski J (June 1999). "Unique multifunctional HSD17B4 gene product: 17beta-hydroxysteroid dehydrogenase 4 and D-3-hydroxyacyl-coenzyme A dehydrogenase/hydratase involved in Zellweger syndrome". Journal of Molecular Endocrinology. 22 (3): 227–40. doi:10.1677/jme.0.0220227. PMID 10343282.
• Huyghe S, Mannaerts GP, Baes M, Van Veldhoven PP (September 2006). "Peroxisomal multifunctional protein-2: the enzyme, the patients and the knockout mouse model". Biochimica et Biophysica Acta. 1761 (9): 973–94. doi:10.1016/j.bbalip.2006.04.006. PMID 16766224.
• Palosaari PM, Hiltunen JK (February 1990). "Peroxisomal bifunctional protein from rat liver is a trifunctional enzyme possessing 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2-enoyl-CoA isomerase activities". The Journal of Biological Chemistry. 265 (5): 2446–9. PMID 2303409.
• Adamski J, Normand T, Leenders F, Monté D, Begue A, Stéhelin D, Jungblut PW, de Launoit Y (October 1995). "Molecular cloning of a novel widely expressed human 80 kDa 17 beta-hydroxysteroid dehydrogenase IV". The Biochemical Journal. 311 ( Pt 2) (2): 437–43. PMC 1136019. PMID 7487879.
• Markus M, Husen B, Adamski J (December 1995). "The subcellular localization of 17 beta-hydroxysteroid dehydrogenase type 4 and its interaction with actin". The Journal of Steroid Biochemistry and Molecular Biology. 55 (5–6): 617–21. doi:10.1016/0960-0760(95)00213-8. PMID 8547189.
• Jiang LL, Kobayashi A, Matsuura H, Fukushima H, Hashimoto T (September 1996). "Purification and properties of human D-3-hydroxyacyl-CoA dehydratase: medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase". Journal of Biochemistry. 120 (3): 624–32. doi:10.1093/oxfordjournals.jbchem.a021458. PMID 8902629.
• Jiang LL, Miyazawa S, Souri M, Hashimoto T (February 1997). "Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein". Journal of Biochemistry. 121 (2): 364–9. doi:10.1093/oxfordjournals.jbchem.a021596. PMID 9089413.
• Jiang LL, Kurosawa T, Sato M, Suzuki Y, Hashimoto T (March 1997). "Physiological role of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein". Journal of Biochemistry. 121 (3): 506–13. doi:10.1093/oxfordjournals.jbchem.a021615. PMID 9133619.
• Novikov D, Dieuaide-Noubhani M, Vermeesch JR, Fournier B, Mannaerts GP, Van Veldhoven PP (May 1997). "The human peroxisomal multifunctional protein involved in bile acid synthesis: activity measurement, deficiency in Zellweger syndrome and chromosome mapping". Biochimica et Biophysica Acta. 1360 (3): 229–40. doi:10.1016/s0925-4439(97)00003-3. PMID 9197465.
• Suzuki Y, Jiang LL, Souri M, Miyazawa S, Fukuda S, Zhang Z, Une M, Shimozawa N, Kondo N, Orii T, Hashimoto T (November 1997). "D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder". American Journal of Human Genetics. 61 (5): 1153–62. doi:10.1086/301599. PMC 1716023. PMID 9345094.
• van Grunsven EG, van Berkel E, Ijlst L, Vreken P, de Klerk JB, Adamski J, Lemonde H, Clayton PT, Cuebas DA, Wanders RJ (March 1998). "Peroxisomal D-hydroxyacyl-CoA dehydrogenase deficiency: resolution of the enzyme defect and its molecular basis in bifunctional protein deficiency". Proceedings of the National Academy of Sciences of the United States of America. 95 (5): 2128–33. doi:10.1073/pnas.95.5.2128. PMC 19272. PMID 9482850.
• Dong Y, Qiu QQ, Debear J, Lathrop WF, Bertolini DR, Tamburini PP (October 1998). "17Beta-hydroxysteroid dehydrogenases in human bone cells". Journal of Bone and Mineral Research. 13 (10): 1539–46. doi:10.1359/jbmr.1998.13.10.1539. PMID 9783542.
• Leenders F, Dolez V, Begue A, Möller G, Gloeckner JC, de Launoit Y, Adamski J (December 1998). "Structure of the gene for the human 17beta-hydroxysteroid dehydrogenase type IV". Mammalian Genome. 9 (12): 1036–41. doi:10.1007/s003359900921. PMID 9880674.
• Green VL, Speirs V, Landolt AM, Foy PM, Atkin SL (April 1999). "17Beta-hydroxysteroid dehydrogenase type 1, 2, 3, and 4 expression and enzyme activity in human anterior pituitary adenomas". The Journal of Clinical Endocrinology and Metabolism. 84 (4): 1340–5. doi:10.1210/jc.84.4.1340. PMID 10199776.
• van Grunsven EG, Mooijer PA, Aubourg P, Wanders RJ (August 1999). "Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional protein deficiency". Human Molecular Genetics. 8 (8): 1509–16. doi:10.1093/hmg/8.8.1509. PMID 10400999.
• Itoh M, Suzuki Y, Takashima S (June 1999). "A novel peroxisomal enzyme, D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein: its expression in the developing human brain". Microscopy Research and Technique. 45 (6): 383–8. doi:10.1002/(SICI)1097-0029(19990615)45:6<383::AID-JEMT5>3.0.CO;2-7. PMID 10402265.
• Möller G, Leenders F, van Grunsven EG, Dolez V, Qualmann B, Kessels MM, Markus M, Krazeisen A, Husen B, Wanders RJ, de Launoit Y, Adamski J (1999). "Characterization of the HSD17B4 gene: D-specific multifunctional protein 2/17beta-hydroxysteroid dehydrogenase IV". The Journal of Steroid Biochemistry and Molecular Biology. 69 (1–6): 441–6. doi:10.1016/S0960-0760(99)00066-7. PMID 10419023.
• Haapalainen AM, van Aalten DM, Meriläinen G, Jalonen JE, Pirilä P, Wierenga RK, Hiltunen JK, Glumoff T (November 2001). "Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution". Journal of Molecular Biology. 313 (5): 1127–38. doi:10.1006/jmbi.2001.5084. PMID 11700068.