Ergosterol synthesis, precursor

Since ergosterol is used in the formation of the leishmanial cell membrane, inhibition of ergosterol biosynthesis has been considered as a useful target for chemotherapeutic attack. Allylamines (eg. terbinafine) and imidazole antifungals (eg. ketoconazole) have been found to interfere with different steps in the biosynthetic pathway of C28 sterols in leishmania and fungi. Allylamines inhibit the microsomal squalene 2,3-epoxidase and, therefore, inhibit the synthesis of squalene epoxide, the precursor of lanosterol. Imidazoles, on other hand, inhibit cytochrome P-450 dependent C-14 demethylation of lanosterol leading to decreased or no synthesis of ergosterol [30]. 

Azoles are fungicidal and interfere with the synthesis of ergosterol by inhibiting the P450-dependent 14 alpha-demethylation of its precursor molecule, lanosterol. 

Figure 7-12 outlines the terminal steps in the complex sequence of both the biosynthesis of cholesterol and ergosterol. The synthesis, starting with acetate, leads to the common steroid precursor lanosterol.9 Thus, in the case of cholesterol, the scheme involves steps for the reduction of the A24 double bond, and the oxidation and removal of the 14a methyl group and of both methyls at C-4. This is followed by isomerization of the A8 double bond of the resultant zygmosterol to the A5 position, affording desmesterol, and finally cholesterol. 

A) Oral bioavailability is affected by first-pass hepatic metabolism Only third-generation cephalosporins cross the blood-brain barrier Procaine penicillin G is the most commonly used intravenous form of the antibiotic Renal tubular reabsorption of beta-lactams is inhibited by probenecid Nafcillin and ceftriaxone are eliminated mainly via biliary secretion The mechanism of antibacterial action of cephalosporins involves (A) Inhibition of the synthesis of precursors of peptidoglycans Interference with the synthesis of ergosterol Inhibition of transpeptidation reactions Inhibition of beta-lactamases Binding to cytoplasmic receptor proteins... 

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