CYP24A1

Cytochrome P450, family 24, subfamily A, polypeptide 1
Identifiers
Symbols	CYP24A1 ; CP24; CYP24; HCAI; P450-CC24
External IDs	OMIM: 126065 MGI: 88593 HomoloGene: 68094 ChEMBL: 4521 GeneCards: CYP24A1 Gene
EC number	1.14.13.126
Gene ontology Molecular function • iron ion binding • 25-hydroxycholecalciferol-24-hydroxylase activity • oxidoreductase activity • heme binding • 1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity Cellular component • mitochondrial inner membrane Biological process • osteoblast differentiation • vitamin metabolic process • xenobiotic metabolic process • steroid metabolic process • response to vitamin D • vitamin D metabolic process • vitamin D catabolic process • small molecule metabolic process • oxidation-reduction process • vitamin D receptor signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1591	13081
Ensembl	ENSG00000019186	ENSMUSG00000038567
UniProt	Q07973	Q64441
RefSeq (mRNA)	NM_000782	NM_009996
RefSeq (protein)	NP_000773	NP_034126
Location (UCSC)	Chr 20: 54.15 – 54.17 Mb	Chr 2: 170.48 – 170.5 Mb
PubMed search

1,25-dihydroxyvitamin D₃ 24-hydroxylase, mitochondrial is an enzyme that in humans is encoded by the CYP24A1 gene.^[1]

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids.

Function

This mitochondrial protein initiates the degradation of 1,25-dihydroxyvitamin D₃, the physiologically active form of vitamin D₃, by hydroxylation of the side chain to form calcitroic acid.

In regulating the level of vitamin D₃, this enzyme plays a role in calcium homeostasis and the vitamin D endocrine system.^[2]

CYP24A1 could play a role in Severe Infantile Hypercalcemia.^[3]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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|{{{bSize}}}px|alt=Vitamin D Synthesis Pathway edit]]

Vitamin D Synthesis Pathway edit

1. The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".

References

1. "Entrez Gene: CYP24A1 cytochrome P450, family 24, subfamily A, polypeptide 1".
2. Sakaki T, Kagawa N, Yamamoto K, Inouye K (January 2005). "Metabolism of vitamin D₃ by cytochromes P450". Front. Biosci. 10: 119–34. doi:10.2741/1514. PMID 15574355.
3. Dauber A, Nguyen TT, Sochett E, Cole DE, Horst R, Abrams SA, Carpenter TO, Hirschhorn JN (February 2012). "Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemia". J. Clin. Endocrinol. Metab. 97 (2): E268–74. doi:10.1210/jc.2011-1972. PMC 3275367. PMID 22112808.

Further reading

• Okuda K, Usui E, Ohyama Y (1995). "Recent progress in enzymology and molecular biology of enzymes involved in vitamin D metabolism.". J. Lipid Res. 36 (8): 1641–52. PMID 7595086.
• Chen KS, DeLuca HF (1995). "Cloning of the human 1 alpha,25-dihydroxyvitamin D-3 24-hydroxylase gene promoter and identification of two vitamin D-responsive elements.". Biochim. Biophys. Acta 1263 (1): 1–9. doi:10.1016/0167-4781(95)00060-t. PMID 7632726.
• Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA; et al. (1995). "Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening.". Genomics 23 (1): 42–50. doi:10.1006/geno.1994.1457. PMID 7829101.
• Chen ML, Heinrich G, Ohyama YI; et al. (1994). "Expression of 25-hydroxyvitamin D3-24-hydroxylase mRNA in cultured human keratinocytes.". Proc. Soc. Exp. Biol. Med. 207 (1): 57–61. PMID 7938037.
• Labuda M, Lemieux N, Tihy F; et al. (1994). "Human 25-hydroxyvitamin D 24-hydroxylase cytochrome P450 subunit maps to a different chromosomal location than that of pseudovitamin D-deficient rickets.". J. Bone Miner. Res. 8 (11): 1397–406. doi:10.1002/jbmr.5650081114. PMID 8266831.
• Hahn CN, Baker E, Laslo P; et al. (1993). "Localization of the human vitamin D 24-hydroxylase gene (CYP24) to chromosome 20q13.2→q13.3.". Cytogenet. Cell Genet. 62 (4): 192–3. doi:10.1159/000133473. PMID 8440135.
• Chen KS, Prahl JM, DeLuca HF (1993). "Isolation and expression of human 1,25-dihydroxyvitamin D3 24-hydroxylase cDNA.". Proc. Natl. Acad. Sci. U.S.A. 90 (10): 4543–7. doi:10.1073/pnas.90.10.4543. PMC 46548. PMID 8506296.
• Bland R, Walker EA, Hughes SV; et al. (1999). "Constitutive expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in a transformed human proximal tubule cell line: evidence for direct regulation of vitamin D metabolism by calcium.". Endocrinology 140 (5): 2027–34. doi:10.1210/en.140.5.2027. PMID 10218951.
• Taniguchi T, Eto TA, Shiotsuki H; et al. (2001). "Newly established assay method for 25-hydroxyvitamin D3 24-hydroxylase revealed much lower Km for 25-hydroxyvitamin D3 than for 1alpha,25-dihydroxyvitamin D3.". J. Bone Miner. Res. 16 (1): 57–62. doi:10.1359/jbmr.2001.16.1.57. PMID 11149490.
• Deloukas P, Matthews LH, Ashurst J; et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20.". Nature 414 (6866): 865–71. doi:10.1038/414865a. PMID 11780052.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Farhan H, Cross HS (2003). "Transcriptional inhibition of CYP24 by genistein.". Ann. N. Y. Acad. Sci. 973: 459–62. doi:10.1111/j.1749-6632.2002.tb04683.x. PMID 12485911.
• Theodoropoulos C, Demers C, Delvin E; et al. (2003). "Calcitriol regulates the expression of the genes encoding the three key vitamin D3 hydroxylases and the drug-metabolizing enzyme CYP3A4 in the human fetal intestine.". Clin. Endocrinol. (Oxf) 58 (4): 489–99. doi:10.1046/j.1365-2265.2003.01743.x. PMID 12641633.
• Fritsche J, Mondal K, Ehrnsperger A; et al. (2004). "Regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase and production of 1 alpha,25-dihydroxyvitamin D3 by human dendritic cells.". Blood 102 (9): 3314–6. doi:10.1182/blood-2002-11-3521. PMID 12855575.
• Nguyen TM, Lieberherr M, Fritsch J; et al. (2004). "The rapid effects of 1,25-dihydroxyvitamin D3 require the vitamin D receptor and influence 24-hydroxylase activity: studies in human skin fibroblasts bearing vitamin D receptor mutations.". J. Biol. Chem. 279 (9): 7591–7. doi:10.1074/jbc.M309517200. PMID 14665637.
• Mimori K, Tanaka Y, Yoshinaga K; et al. (2004). "Clinical significance of the overexpression of the candidate oncogene CYP24 in esophageal cancer.". Ann. Oncol. 15 (2): 236–41. doi:10.1093/annonc/mdh056. PMID 14760115.
• Sawada N, Kusudo T, Sakaki T; et al. (2004). "Novel metabolism of 1 alpha,25-dihydroxyvitamin D3 with C24-C25 bond cleavage catalyzed by human CYP24A1.". Biochemistry 43 (15): 4530–7. doi:10.1021/bi030207f. PMID 15078099.
• Kusudo T, Sakaki T, Abe D; et al. (2004). "Metabolism of A-ring diastereomers of 1alpha,25-dihydroxyvitamin D3 by CYP24A1.". Biochem. Biophys. Res. Commun. 321 (4): 774–82. doi:10.1016/j.bbrc.2004.07.040. PMID 15358094.
• Pascussi JM, Robert A, Nguyen M; et al. (2005). "Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia.". J. Clin. Invest. 115 (1): 177–86. doi:10.1172/JCI200521867. PMC 539191. PMID 15630458.