Ergosterol biosynthesis

Ergosterol, one of the most important components in fungal membranes, is involved in numerous biological functions, such as membrane fluidity regulation, activity and distribution of integral proteins and control of the cellular cycle. Ergosterol pathway is fungal-specific; plasma membranes of other organisms are composed predominantly of other types of sterol. However, the pathway is not universally present in fungi; for example, Pneumocystis carinii plasma membranes lack ergosterol. In S. cerevisiae, some steps in the pathway are dispensible while others are essential for viability (Tan et al., 2003).

Biosynthesis of ergosterol similarly to carotenoids and other isoprenoid compounds (e. g. ubiquinone), is derived from acetyl-CoA in a three-stage synthehtic process (Metzler, 2003). Stage one is the synthesis of isopenthenyl pyrophosphate (IPP), an activated isoprene unit that is the key building block of ergosterol. This step is identical with mevalonate pathway (Figure 9). Stage two is the condensation of six molecules of IPP to form squalene. In the stage three, squalene cyclizes in an astounding reaction and the tetracyclic product is subsequently converted into ergosterol. In the ergosterol pathway, steps prior to squalene formation are important for pathway regulation and early intermediates are metabolized to produce other essential cellular components (Tan et al, 2003). It should be noted that isoprenoid pathway is of great importance in secondary metabolism. Combination of C5 IPP units to squalene exemplifies a fundamental mechanism for the assembly of carbon skeletons in biomolecules. A remarkable array of compounds is formed from IPP, the basic C5 building block. Several molecules contain isporenoid side chains, for example Coenzyme Q10 has a side chain made ud of 10 isporene units.