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 HSD17B4gene.[1][2][3][4] It is involved in fatty acidβ-oxidation and steroidmetabolism.[4]
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][3]
↑Leenders F, Prescher G, Dolez V, Begue A, de Launoit Y, Adamski J (Mar 1997). "Assignment of human 17 beta-hydroxysteroid dehydrogenase IV to chromosome 5q2 by fluorescence in situ hybridization". Genomics. 37 (3): 403–4. doi:10.1006/geno.1996.0578. PMID8938456.
↑ 4.04.1Huyghe S, Mannaerts GP, Baes M, Van Veldhoven PP (2006). "Peroxisomal multifunctional protein-2: the enzyme, the patients and the knockout mouse model". Biochim. Biophys. Acta. 1761 (9): 973–94. doi:10.1016/j.bbalip.2006.04.006. PMID16766224.
Further reading
de Launoit Y, Adamski J (1999). "Unique multifunctional HSD17B4 gene product: 17beta-hydroxysteroid dehydrogenase 4 and D-3-hydroxyacyl-coenzyme A dehydrogenase/hydratase involved in Zellweger syndrome". J. Mol. Endocrinol. 22 (3): 227–40. doi:10.1677/jme.0.0220227. PMID10343282.
Huyghe S, Mannaerts GP, Baes M, Van Veldhoven PP (2006). "Peroxisomal multifunctional protein-2: the enzyme, the patients and the knockout mouse model". Biochim. Biophys. Acta. 1761 (9): 973–94. doi:10.1016/j.bbalip.2006.04.006. PMID16766224.
Palosaari PM, Hiltunen JK (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". J. Biol. Chem. 265 (5): 2446–9. PMID2303409.
Markus M, Husen B, Adamski J (1996). "The subcellular localization of 17 beta-hydroxysteroid dehydrogenase type 4 and its interaction with actin". J. Steroid Biochem. Mol. Biol. 55 (5–6): 617–21. doi:10.1016/0960-0760(95)00213-8. PMID8547189.
Jiang LL, Kobayashi A, Matsuura H, et al. (1997). "Purification and properties of human D-3-hydroxyacyl-CoA dehydratase: medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase". J. Biochem. 120 (3): 624–32. doi:10.1093/oxfordjournals.jbchem.a021458. PMID8902629.
Jiang LL, Miyazawa S, Souri M, Hashimoto T (1997). "Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein". J. Biochem. 121 (2): 364–9. doi:10.1093/oxfordjournals.jbchem.a021596. PMID9089413.
Jiang LL, Kurosawa T, Sato M, et al. (1997). "Physiological role of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein". J. Biochem. 121 (3): 506–13. doi:10.1093/oxfordjournals.jbchem.a021615. PMID9133619.
Novikov D, Dieuaide-Noubhani M, Vermeesch JR, et al. (1997). "The human peroxisomal multifunctional protein involved in bile acid synthesis: activity measurement, deficiency in Zellweger syndrome and chromosome mapping". Biochim. Biophys. Acta. 1360 (3): 229–40. doi:10.1016/s0925-4439(97)00003-3. PMID9197465.
Dong Y, Qiu QQ, Debear J, et al. (1999). "17Beta-hydroxysteroid dehydrogenases in human bone cells". J. Bone Miner. Res. 13 (10): 1539–46. doi:10.1359/jbmr.1998.13.10.1539. PMID9783542.
Leenders F, Dolez V, Begue A, et al. (1999). "Structure of the gene for the human 17beta-hydroxysteroid dehydrogenase type IV". Mamm. Genome. 9 (12): 1036–41. doi:10.1007/s003359900921. PMID9880674.
Green VL, Speirs V, Landolt AM, et al. (1999). "17Beta-hydroxysteroid dehydrogenase type 1, 2, 3, and 4 expression and enzyme activity in human anterior pituitary adenomas". J. Clin. Endocrinol. Metab. 84 (4): 1340–5. doi:10.1210/jc.84.4.1340. PMID10199776.
van Grunsven EG, Mooijer PA, Aubourg P, Wanders RJ (1999). "Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional protein deficiency". Hum. Mol. Genet. 8 (8): 1509–16. doi:10.1093/hmg/8.8.1509. PMID10400999.
Itoh M, Suzuki Y, Takashima S (1999). "A novel peroxisomal enzyme, D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein: its expression in the developing human brain". Microsc. Res. Tech. 45 (6): 383–8. doi:10.1002/(SICI)1097-0029(19990615)45:6<383::AID-JEMT5>3.0.CO;2-7. PMID10402265.
Möller G, Leenders F, van Grunsven EG, et al. (1999). "Characterization of the HSD17B4 gene: D-specific multifunctional protein 2/17beta-hydroxysteroid dehydrogenase IV". J. Steroid Biochem. Mol. Biol. 69 (1–6): 441–6. doi:10.1016/S0960-0760(99)00066-7. PMID10419023.
Haapalainen AM, van Aalten DM, Meriläinen G, et al. (2001). "Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution". J. Mol. Biol. 313 (5): 1127–38. doi:10.1006/jmbi.2001.5084. PMID11700068.
