These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Molecular diversity of sterol 14alpha-demethylase substrates in plants, fungi and humans.
    Author: Lamb DC, Kelly DE, Kelly SL.
    Journal: FEBS Lett; 1998 Mar 27; 425(2):263-5. PubMed ID: 9559662.
    Abstract:
    Metabolism of lanosterol (LAN), 24-methylene-24,25-dihydrolanosterol (24-methyleneDHL), dihydrolanosterol (DHL) and obtusifoliol (OBT) by purified human, plant (Sorghum bicolor) and fungal (Candida albicans) sterol 14alpha-demethylase (CYP51; P450(14DM)) reconstituted with NADPH cytochrome P450 reductases was studied in order to elucidate the substrate specificity and sterol stereo- and regio-structural requirements for optimal CYP51 activity. Both human and C. albicans CYP51 could catalyse 14alpha-demethylation of each substrate with varying levels of activity, but having slightly higher activity for their respective endogenous substrates in vivo, dihydrolanosterol for human CYP51 (Vmax = 0.5 nmol/min/nmol CYP51) and 24-methylene-24,25-dihydrolanosterol for C. albicans CYP51 (Vmax = 0.3 nmol/min/nmol CYP51). In contrast, S. bicolor CYP51 showed strict substrate specificity and selectivity towards its own endogenous substrate, obtusifoliol (Vmax = 5.5 nmol/min/nmol CYP51) and was inactive towards 14alpha-demethylation of lanosterol, 24-methylene-24,25-dihydrolanosterol and dihydrolanosterol. These findings confirm that the presence of the 4beta-methyl group in the sterol molecule renders the plant CYP51 incapable of 14alpha-demethylation thus revealing the strict active site conservation of plant CYP51 during evolution.
    [Abstract] [Full Text] [Related] [New Search]