HSD17B4 explained

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.^{[1] [2] [3] [4]} 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]^[5]

See also

• D-bifunctional protein deficiency
• Perrault syndrome

Further reading

• de Launoit Y, Adamski J . 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 . June 1999 . 10343282 . 10.1677/jme.0.0220227 . free .
• Huyghe S, Mannaerts GP, Baes M, Van Veldhoven PP . Peroxisomal multifunctional protein-2: the enzyme, the patients and the knockout mouse model . Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids . 1761 . 9 . 973–94 . September 2006 . 16766224 . 10.1016/j.bbalip.2006.04.006 .
• Palosaari PM, Hiltunen JK . 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 . February 1990 . 10.1016/S0021-9258(19)39819-9 . 2303409 . free .
• 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 . The Biochemical Journal . 311 (Pt 2) . 2 . 437–43 . October 1995 . 7487879 . 1136019 . 10.1042/bj3110437.
• Markus M, Husen B, Adamski J . 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 . December 1995 . 8547189 . 10.1016/0960-0760(95)00213-8 . 36279864 .
• 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 . Journal of Biochemistry . 120 . 3 . 624–32 . September 1996 . 8902629 . 10.1093/oxfordjournals.jbchem.a021458 .
• Jiang LL, Miyazawa S, Souri M, Hashimoto T . Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein . Journal of Biochemistry . 121 . 2 . 364–9 . February 1997 . 9089413 . 10.1093/oxfordjournals.jbchem.a021596 .
• 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 . Journal of Biochemistry . 121 . 3 . 506–13 . March 1997 . 9133619 . 10.1093/oxfordjournals.jbchem.a021615 . free .
• Novikov D, Dieuaide-Noubhani M, Vermeesch JR, Fournier B, Mannaerts GP, Van Veldhoven PP . The human peroxisomal multifunctional protein involved in bile acid synthesis: activity measurement, deficiency in Zellweger syndrome and chromosome mapping . Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease . 1360 . 3 . 229–40 . May 1997 . 9197465 . 10.1016/s0925-4439(97)00003-3 . free .
• Suzuki Y, Jiang LL, Souri M, Miyazawa S, Fukuda S, Zhang Z, Une M, Shimozawa N, Kondo N, Orii T, Hashimoto T . 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 . November 1997 . 9345094 . 1716023 . 10.1086/301599 .
• van Grunsven EG, van Berkel E, Ijlst L, Vreken P, de Klerk JB, Adamski J, Lemonde H, Clayton PT, Cuebas DA, Wanders RJ . 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 . March 1998 . 9482850 . 19272 . 10.1073/pnas.95.5.2128 . 1998PNAS...95.2128V . free .
• Dong Y, Qiu QQ, Debear J, Lathrop WF, Bertolini DR, Tamburini PP . 17Beta-hydroxysteroid dehydrogenases in human bone cells . Journal of Bone and Mineral Research . 13 . 10 . 1539–46 . October 1998 . 9783542 . 10.1359/jbmr.1998.13.10.1539 . 85168465 . free .
• Leenders F, Dolez V, Begue A, Möller G, Gloeckner JC, de Launoit Y, Adamski J . Structure of the gene for the human 17beta-hydroxysteroid dehydrogenase type IV . Mammalian Genome . 9 . 12 . 1036–41 . December 1998 . 9880674 . 10.1007/s003359900921 . 31749993 .
• Green VL, Speirs V, Landolt AM, Foy PM, Atkin SL . 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 . April 1999 . 10.1210/jcem.84.4.5619 . 10199776 . Valerie Speirs . free .
• van Grunsven EG, Mooijer PA, Aubourg P, Wanders RJ . Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional protein deficiency . Human Molecular Genetics . 8 . 8 . 1509–16 . August 1999 . 10400999 . 10.1093/hmg/8.8.1509 . free .
• Itoh M, Suzuki Y, Takashima S . 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 . June 1999 . 10402265 . 10.1002/(SICI)1097-0029(19990615)45:6<383::AID-JEMT5>3.0.CO;2-7 . 26589734 .
• 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 . 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 . 1999 . 10419023 . 10.1016/S0960-0760(99)00066-7 . 33700582 .
• Haapalainen AM, van Aalten DM, Meriläinen G, Jalonen JE, Pirilä P, Wierenga RK, Hiltunen JK, Glumoff T . 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 . November 2001 . 11700068 . 10.1006/jmbi.2001.5084 . 10.1.1.417.9893 .

Notes and References

1. Leenders F, Prescher G, Dolez V, Begue A, de Launoit Y, Adamski J . Assignment of human 17 beta-hydroxysteroid dehydrogenase IV to chromosome 5q2 by fluorescence in situ hybridization . Genomics . 37 . 3 . 403–4 . November 1996 . 8938456 . 10.1006/geno.1996.0578 .
2. Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jörnvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U . The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative . Chemico-Biological Interactions . 178 . 1–3 . 94–8 . March 2009 . 19027726 . 2896744 . 10.1016/j.cbi.2008.10.040 . 2009CBI...178...94P .
3. Web site: Entrez Gene: HSD17B4 hydroxysteroid (17-beta) dehydrogenase 4.
4. Huyghe S, Mannaerts GP, Baes M, Van Veldhoven PP . Peroxisomal multifunctional protein-2: the enzyme, the patients and the knockout mouse model . Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids . 1761 . 9 . 973–94 . September 2006 . 16766224 . 10.1016/j.bbalip.2006.04.006 .
5. Web site: Entrez Gene: HSD17B4 hydroxysteroid (17-beta) dehydrogenase 4.