Biosynthesis sterol

D. Berg and M. Plempel, eds.. Sterol Biosynthesis Inhibitors—Pharmaceutical and Agrochemical Aspects, Ellis Horwood, Chichester, 1988. 

G. Haug and H. Hoffman, eds., Chemisty of Plant Protection, Hoi 1 Sterol Biosynthesis Inhibitors andMnti-Feeding Compounds, Springer-Vedag, Berlin, 1986. 

The biosynthetic pathways for sterol biosynthesis have been known for a long time and a brief summary is presented in Scheme l.3 Starting from acetyl CoA (2), acetoacetyl CoA, and... 

Squalene epoxidase, like most enzymes responsible for the later steps of sterol biosynthesis [43, 51], is membrane-bound which makes its purification in native form challenging. The purification is additionally complicated by the presence of a large number of cytochrome P450 and other enzymes that have similar hydro-phobicity and size as squalene epoxidase and are hence difficult to remove [52]. Most studies have been carried out with rat liver microsome squalene epoxidase either partially purified or as a homogenate of the cell membrane fraction. In vitro reconstitution of squalene epoxidase activity is absolutely dependent on molecular oxygen, NADPH, FAD, and NADPH-cytochrome c reductase [52, 53]. In this respect, squalene epoxidase resembles the cytochrome P450 enzymes described... 

Kato, T. (1986). Sterol biosynthesis in fungi A target for broad spectrum fungicides. In Chemistry of Plant Protection No. 1 Sterol Biosynthesis Inhibitors and Anti-feeding Compounds. Berlin Springer-Verlag, 1-24. 

This synthetic allylamine derivative inhibits the enzyme squalene epoxidase at an early stage in fungal sterol biosynthesis. Acting as a structural analogue of squalene, naffidine causes the accumulation of this unsaturated hydrocarbon, and a decrease in ergosterol in the fungal cell membrane. 

Imibenconazole is a triazole fungicide exhibiting direct cell membrane destruction as well as sterol biosynthesis inhibition for controlling major diseases of fruits, vegetables, cereals, ornamentals and turf. 

Piironen V et al (2000) Plant sterols biosynthesis, biological function and their importance to human nutrition. J Sci Food Agric 80(7) 939—966... 

Steroid chemistry, the glamor area of natural product research in the years following World War II, was replaced by macrolides, alkaloids, and prostanoids. Sterol chemistry again became exciting when an unanticipated rich diversity of marine invertebrate sterols were isolated, notably from sponges. After pioneering research in Italy, the field was reborn in Carl Djerassi s laboratory at Stanford. As a result, we now have a better and more detailed knowledge of sterol biosynthesis than of any other class of marine natural products. The authors of Chapter 1 are Stanford alumni. 

Biosynthesis of Sterol-Related Triterpenes - De Novo Sterol Biosynthesis... 

Unquestionably, the greatest amount of research activity in sterol biosynthesis has been devoted to the elucidation of metabolic origins of unconventional... 

A recent and surprising finding in sponge sterol biosynthesis is the observation that certain 24-alkyl sterols can be transformed to cholesterol [46,48, 50]. This is particularly unusual, as this pathway operates in organisms which are also... 

There is a single report of the dealkylation of a sterol side-chain in the whelk Buccinum undatum [52]. This organism also transformed 3H-lanosterol (33) to cholesterol (1), thus indicating its capability for de novo sterol biosynthesis. 

Genetic analysis indicates that two of the 10 sad mutants of A. strigosa that we isolated represent different mutant alleles at the Sadi locus.6 These mutants accumulate radiolabelled 2,3-oxidosqualene but not p-amyrin when the roots are fed with 14C-labelled precursor mevalonic acid, suggesting that the triterpenoid pathway is blocked between 2,3-oxidosqualene and P-amyrin.34 The roots of these mutants also lack detectable P-amyrin synthase activity, but, like the wild type and the other mutants, are unimpaired in cycloartenol synthase (CS) activity and sterol biosynthesis.34 The transcript levels for AsbASl are substantially reduced in roots of sadl mutants, while AsCSl transcript levels are unaffected,35 suggesting that the sadl mutants are either mutated in the AsbASl gene itself or in a gene involved in its regulation. 

Chagas disease is caused by a kinetoplastid trypanosoma parasite and affects millions of people in Latin America. The disease is currently incurable. Chemotherapy is based mainly on nitrofuran and nitroimidazole compounds and sterol biosynthesis inhibitors such as ketoconazole (337). Toxicity and high doses are the major problems for these organic drugs. Urbina et al. (338, 339) have found that com-plexation of antiparasitic organic agents such as chloroquine (78)... 

Pharmacologically active allenic steroids have already been examined intensively for about 30 years [5], Thus, the only naturally occurring allenic steroid 107 had been synthesized 3 years before its isolation from Callyspongia diffusa and it had been identified as an inhibitor of the sterol biosynthesis of the silkworm Bombyx mori (Scheme 18.34) [86d], At this early stage, allenic 3-oxo-5,10-secosteroids of type 108 were also used for the irreversible inhibition of ketosteroid isomerases in bacteria, assuming that their activity is probably caused by Michael addition of a nucleophilic amino acid side chain of the enzyme at the 5-position of the steroid [103, 104]. Since this activity is also observed in the corresponding /3,y-acetylenic ketones, it can be rationalized that the latter are converted in vivo into the allenic steroids 108 by enzymatic isomerization [104, 105],... 

Scheme 18.34 Allenic steroids as inhibitors of sterol biosynthesis.

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