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CYP51A1  -  cytochrome P450, family 51, subfamily A,...

Homo sapiens

Synonyms: CP51, CYP51, CYPL1, CYPLI, Cytochrome P450 51A1, ...
 
 
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Disease relevance of CYP51A1

 

High impact information on CYP51A1

  • In all subgroups, insulin led to an increase in PM glucose transporters and a corresponding depletion of transporters in the LDM [4].
  • Insulin recruited 20% fewer transporters to the PM in the obese subgroup when compared with lean controls, and this was associated with a decline in LDM transporters with enlarging cell size in the control subjects [4].
  • Glucose transporters were measured in plasma membrane (PM), low-density (LDM), and high-density (HDM) microsomal subfractions from basal and maximally insulin-stimulated cells using the cytochalasin B binding assay, and normalized per milligram of membrane protein [4].
  • In NIDDM, PM, and LDM, transporters were decreased 50% in both basal and stimulated cells when compared with obese controls having similar mean adipocyte size [4].
  • CYP51 sterol demethylases are the only cytochrome P450 enzymes with a conserved function across the animal, fungal, and plant kingdoms (in the synthesis of essential sterols) [5].
 

Chemical compound and disease context of CYP51A1

  • C-terminal truncation of Candida albicans and human CYP51 orthologs reveals that, despite conservation in sequence, the requirement for arginine at the homologous C-terminal position in folding in E. coli is not conserved [6].
  • The genetic locus encoding cytochrome P450 51 (CYP51; P450(14DM)) in Mycobacterium smegmatis is described here together with confirmation of activity in lanosterol 14 alpha-demethylation [7].
  • Evidence for this has included association with maternal luteomas, fetal 21-hydroxylase deficiency, early pregnancy exposure to high-dose fluconazole, lanosterol 14-alpha-demethylase deficiency, and a unique urinary steroid profile consistent with apparent pregnene hydroxylation deficiency (APHD) [8].
 

Biological context of CYP51A1

 

Anatomical context of CYP51A1

 

Associations of CYP51A1 with chemical compounds

  • This selection, which was coupled with a test of susceptibility to the azole derivatives fluconazole, ketoconazole, and itraconazole, enabled the detection of mutations in different cloned CYP51A1 genes, whose products are potentially affected in their affinity for azole derivatives [13].
  • The cytochrome P-450 lanosterol 14alpha-demethylase (CYP51A1) of yeasts is involved in an important step in the biosynthesis of ergosterol [13].
  • In fungal pathogens of cereals, CYP51A1 modifications, some at positions known to contribute to a resistant phenotype in human pathogens, have also been identified in isolates with altered triazole-sensitivity [14].
  • Fluconazole was observed to inhibit sterol 14 alpha-demethylase in the human pathogen Cryptococcus neoformans, and accumulation of a ketosteroid product was associated with growth arrest [15].
  • In the case of CYP51, cholesterol deprivation led to a 2.6- to 3.8-fold induction of mRNA levels in human adrenocortical H295R cells and this effect was suppressed by the addition of 25-hydroxycholesterol [1].
 

Regulatory relationships of CYP51A1

 

Other interactions of CYP51A1

  • While SREBP-1a and the CRE-bound proteins are essential for the SREBP-dependent response, Sp1 apparently functions only to maximize sterol regulation of CYP51 [9].
  • Using a DNA probe containing all three regulatory elements, it is found that SREBP-1a, a CREB-like factor, and specificity protein (Sp1) all probably bind the CYP51 promoter [9].
  • The presence of strong CYP51 (log-rank = 12.11, P = 0.0005) or strong CYP2S1 (log-rank = 6.72, P = 0.0095) immunoreactivity were associated with poor prognosis [16].
  • Expression levels of four key enzymes of cholesterol metabolism, namely 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, lanosterol 14-demethylase (CYP51), cholesterol 7alpha-hydroxylase (CYP7A1) and sterol 12alpha-hydroxylase (CYP8B1), in metabolic syndrome model rats (SHR/NDmcr-cp) were examined [17].
  • For example, CYP51 is an ER enzyme in majority of tissues but in male germ cells it trafficks through the Golgi to acrosome, where it is stabilized for several weeks [18].
 

Analytical, diagnostic and therapeutic context of CYP51A1

References

  1. The ubiquitously expressed human CYP51 encodes lanosterol 14 alpha-demethylase, a cytochrome P450 whose expression is regulated by oxysterols. Strömstedt, M., Rozman, D., Waterman, M.R. Arch. Biochem. Biophys. (1996) [Pubmed]
  2. CYP51 from Trypanosoma cruzi: a phyla-specific residue in the B' helix defines substrate preferences of sterol 14alpha-demethylase. Lepesheva, G.I., Zaitseva, N.G., Nes, W.D., Zhou, W., Arase, M., Liu, J., Hill, G.C., Waterman, M.R. J. Biol. Chem. (2006) [Pubmed]
  3. Sex differences in the effect of diabetes duration on coronary heart disease mortality. Natarajan, S., Liao, Y., Sinha, D., Cao, G., McGee, D.L., Lipsitz, S.R. Arch. Intern. Med. (2005) [Pubmed]
  4. Role of glucose transporters in the cellular insulin resistance of type II non-insulin-dependent diabetes mellitus. Garvey, W.T., Huecksteadt, T.P., Matthaei, S., Olefsky, J.M. J. Clin. Invest. (1988) [Pubmed]
  5. A different function for a member of an ancient and highly conserved cytochrome P450 family: From essential sterols to plant defense. Qi, X., Bakht, S., Qin, B., Leggett, M., Hemmings, A., Mellon, F., Eagles, J., Werck-Reichhart, D., Schaller, H., Lesot, A., Melton, R., Osbourn, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Folding requirements are different between sterol 14alpha-demethylase (CYP51) from Mycobacterium tuberculosis and human or fungal orthologs. Lepesheva, G.I., Podust, L.M., Bellamine, A., Waterman, M.R. J. Biol. Chem. (2001) [Pubmed]
  7. Conservation and cloning of CYP51: a sterol 14 alpha-demethylase from Mycobacterium smegmatis. Jackson, C.J., Lamb, D.C., Marczylo, T.H., Parker, J.E., Manning, N.L., Kelly, D.E., Kelly, S.L. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  8. Undetectable maternal serum uE3 and postnatal abnormal sterol and steroid metabolism in Antley-Bixler syndrome. Cragun, D.L., Trumpy, S.K., Shackleton, C.H., Kelley, R.I., Leslie, N.D., Mulrooney, N.P., Hopkin, R.J. Am. J. Med. Genet. A (2004) [Pubmed]
  9. A cAMP-responsive element binding site is essential for sterol regulation of the human lanosterol 14alpha-demethylase gene (CYP51). Halder, S.K., Fink, M., Waterman, M.R., Rozman, D. Mol. Endocrinol. (2002) [Pubmed]
  10. The three human cytochrome P450 lanosterol 14 alpha-demethylase (CYP51) genes reside on chromosomes 3, 7, and 13: structure of the two retrotransposed pseudogenes, association with a line-1 element, and evolution of the human CYP51 family. Rozman, D., Strömstedt, M., Waterman, M.R. Arch. Biochem. Biophys. (1996) [Pubmed]
  11. Cyclic adenosine 3',5'-monophosphate(cAMP)/cAMP-responsive element modulator (CREM)-dependent regulation of cholesterogenic lanosterol 14alpha-demethylase (CYP51) in spermatids. Rozman, D., Fink, M., Fimia, G.M., Sassone-Corsi, P., Waterman, M.R. Mol. Endocrinol. (1999) [Pubmed]
  12. Localisation of lanosterol 14alpha-demethylase in round and elongated spermatids of the mouse testis: an immunoelectron microscopic and stereological study. Cotman, M., Rozma, D., Banek, L., Jezek, D. Pflugers Arch. (2001) [Pubmed]
  13. Amino acid substitutions in the cytochrome P-450 lanosterol 14alpha-demethylase (CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents. Sanglard, D., Ischer, F., Koymans, L., Bille, J. Antimicrob. Agents Chemother. (1998) [Pubmed]
  14. Impact of changes in the target P450 CYP51 enzyme associated with altered triazole-sensitivity in fungal pathogens of cereal crops. Cools, H.J., Fraaije, B.A., Kim, S.H., Lucas, J.A. Biochem. Soc. Trans. (2006) [Pubmed]
  15. Cross-resistance to polyene and azole drugs in Cryptococcus neoformans. Joseph-Horne, T., Hollomon, D., Loeffler, R.S., Kelly, S.L. Antimicrob. Agents Chemother. (1995) [Pubmed]
  16. Cytochrome p450 profile of colorectal cancer: identification of markers of prognosis. Kumarakulasingham, M., Rooney, P.H., Dundas, S.R., Telfer, C., Melvin, W.T., Curran, S., Murray, G.I. Clin. Cancer Res. (2005) [Pubmed]
  17. STUDIES ON THE EXPRESSION LEVELS OF STEROL-METABOLIZING ENZYMES IN THE OBESE MODEL SHR/NDmcr-cp RATS. Kudo, M., Noshiro, M., Aoyama, Y., Yoshida, Y. Clin. Exp. Pharmacol. Physiol. (2004) [Pubmed]
  18. Mammalian cytochromes P450-Importance of tissue specificity. Seliskar, M., Rozman, D. Biochim. Biophys. Acta (2007) [Pubmed]
  19. Biological spectra analysis: Linking biological activity profiles to molecular structure. Fliri, A.F., Loging, W.T., Thadeio, P.F., Volkmann, R.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  20. Elevated expression of lanosterol 14alpha-demethylase (CYP51) and the synthesis of oocyte meiosis-activating sterols in postmeiotic germ cells of male rats. Strömstedt, M., Waterman, M.R., Haugen, T.B., Taskén, K., Parvinen, M., Rozman, D. Endocrinology (1998) [Pubmed]
 
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