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Pathway Description
Corticosterone Methyl Oxidase II Deficiency (CMO II)
Homo sapiens
Disease Pathway
Corticosterone methyloxidase type II (CMO-II) deficiency, also called 18-oxidase defiency or aldosterone deficiency II among other names, is a genetic disorder that is autosomally linked. It is caused by a mutation in the cytochrome P450 11B2 gene, whose protein product is responsible for the formation of aldosterone from 18-hydroxycorticosterone (18-OHB), as well as converting progesterone to 11b-hydroxyprogesterone. The conversion of 18-OHB to aldosterone is the only reaction that uses 18-OHB, and due to the enzyme not being entirely functional, it builds up in the cell, while aldosterone levels will be lowered. However, since progesterone and 11b-hydroxyprogesterone are both produced and used by other reactions, their levels in the cell are not changed as drastically. Compared to the CMO-I deficiency, the CMO-II deficiency has less severe mutations in the gene, which cause it to have less severe changes in aldosterone and 18-OHB concentrations.
The CMO-II deficiency, and its resulting aldosterone deficiency can cause a salt-wasting phenotype in children, due to aldosterone being responsible for the resorption of sodium in the body, as well as secretion of potassium. With levels of aldosterone being lower due to this deficiency, excess sodium is excreted in the urine, and higher than average levels of potassium in the serum. Aside salt-wasting and potential failure to thrive as an infant due to this, there are no symptoms, such as genital abnormalities, that are seen in similar salt-wasting disorders like CYP21 deficiency.
References
Corticosterone Methyl Oxidase II Deficiency (CMO II) References
[Metagen: CORTICOSTERONE METHYL OXIDASE II DEFICIENCY - CMO II](http://metagene.de/program/d.prg?id_d=487)
[OMIM: 124080](http://omim.org/entry/610600})
Portrat-Doyen S, Tourniaire J, Richard O, Mulatero P, Aupetit-Faisant B, Curnow KM, Pascoe L, Morel Y: Isolated aldosterone synthase deficiency caused by simultaneous E198D and V386A mutations in the CYP11B2 gene. J Clin Endocrinol Metab. 1998 Nov;83(11):4156-61. doi: 10.1210/jcem.83.11.5258.
Pubmed: 9814506
Picco P, Garibaldi L, Cotellessa M, DiRocco M, Borrone C: Corticosterone methyl oxidase type II deficiency: a cause of failure to thrive and recurrent dehydration in early infancy. Eur J Pediatr. 1992 Mar;151(3):170-3.
Pubmed: 1601005
Zhang G, Rodriguez H, Fardella CE, Harris DA, Miller WL: Mutation T318M in the CYP11B2 gene encoding P450c11AS (aldosterone synthase) causes corticosterone methyl oxidase II deficiency. Am J Hum Genet. 1995 Nov;57(5):1037-43.
Pubmed: 7485152
Steroidogenesis References
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Norman, A.W, and Litwack, G. Hormones (2nd ed.) (1997) San Diego : Academic Press.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (4th ed.) (2002) Amsterdam; Boston: Elsevier.
Miller WL: Molecular biology of steroid hormone synthesis. Endocr Rev. 1988 Aug;9(3):295-318. doi: 10.1210/edrv-9-3-295.
Pubmed: 3061784
HECHTER O, SOLOMON MM, ZAFFARONI A, PINCUS G: Transformation of cholesterol and acetate to adrenal cortical hormones. Arch Biochem Biophys. 1953 Sep;46(1):201-14. doi: 10.1016/0003-9861(53)90182-9.
Pubmed: 13092959
Luu-The V: Assessment of steroidogenesis and steroidogenic enzyme functions. J Steroid Biochem Mol Biol. 2013 Sep;137:176-82. doi: 10.1016/j.jsbmb.2013.05.017. Epub 2013 Jun 13.
Pubmed: 23770321
George FW, Russell DW, Wilson JD: Feed-forward control of prostate growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5 alpha-reductase. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8044-7. doi: 10.1073/pnas.88.18.8044.
Pubmed: 1654556
Andersson S, Berman DM, Jenkins EP, Russell DW: Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism. Nature. 1991 Nov 14;354(6349):159-61. doi: 10.1038/354159a0.
Pubmed: 1944596
Emanuelsson I, Almokhtar M, Wikvall K, Gronbladh A, Nylander E, Svensson AL, Fex Svenningsen A, Norlin M: Expression and regulation of CYP17A1 and 3beta-hydroxysteroid dehydrogenase in cells of the nervous system: Potential effects of vitamin D on brain steroidogenesis. Neurochem Int. 2018 Feb;113:46-55. doi: 10.1016/j.neuint.2017.11.007. Epub 2017 Nov 21.
Pubmed: 29162485
Kimoto T, Asou H, Ohta Y, Mukai H, Chernogolov AA, Kawato S: Digital fluorescence imaging of elementary steps of neurosteroid synthesis in rat brain glial cells. J Pharm Biomed Anal. 1997 Jun;15(9-10):1231-40.
Pubmed: 9226548
Verschoor-Klootwyk AH, Verschoor L, Azhar S, Reaven GM: Role of exogenous cholesterol in regulation of adrenal steroidogenesis in the rat. J Biol Chem. 1982 Jul 10;257(13):7666-71.
Pubmed: 6282849
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