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Sterol 58-isomerase

Paul R, et al. (1998) Both the immunosuppressant SR31747 and the antiestrogen tamoxifen bind to an emopamil-insensitive site of mammalian Delta8-Delta7 sterol isomerase. J. Pharmacol. Exp. Then 285 1296-1302. [Pg.206]

J. M. J. Derry, E. Gormally, G. D. Means, et al. Mutations in a A -A sterol isomerase in the tattered mouse and X-linked dominant chondrodysplasia punctata. Nature Genetics 22, 286 (1999). [Pg.427]

FIGURE 1. Proposed reaction pathway for A -sterol-A -reductase. Structural and chai ge analogies between the cationic high energy intennediates involved in A 7-sterol A7-reductase (a7-SR), cycloeucalenol isomerase (COI), A8ri4 sterol Al4-reductase (A14-SR), and A -A 7-sterol isomerase (A -A 7-SI) and the protonated forms of tridemorph 1, 6,7-diazacholest-8(14)-en-3(3-ol 2 and 6-aza-B-homocholest-7-en-3p-ol 3. [Pg.187]

Both nutritional and metabolic effects play a role, although not all interrelations are well understood at present. There are even patients with low cholesterol levels in whom no underlying cause has been found yet. All patients with hypocholesterolemia should be screened for biosynthesis defects as there have been a number of other conditions identified affecting the biosynthetic pathway [15]. These defects comprise the Conradi-Hiinermann syndrome (sterol isomerase), CHILD syndrome (sterol C-4 demethy-lase), desmosterolosis (sterol 5 -reductase), Greenberg skeletal dysplasia (sterol (5 -reductase), and sitosterolemia. [Pg.58]

Ag-isomerase leading to depletion of ergosterol and accumulation of an unplanar sterol ignosterol. With the inhibition of two steps in the same pathway, a natural synergistic effect is built into the molecule so that the risk of appearance of resistant mutants is low and efficacy high. [Pg.132]

The compensatory effect of cholesterol observed in D407 cells have also been demonstrated in other cell lines (Cho et al. 1998 Holleran et al. 1998) and may well be a consequence of tamoxifen-induced severe inhibition of lanosterol (to cholesterol)-converting enzymes. In rat liver preparations and CHO cells, sterol A8-isomerase (IC50 0.21-0.15. iM) was the most sensitive... [Pg.105]

Cho SY, Kim JH, Paik YK (1998) Cholesterol biosynthesis from lanosterol differential inhibition of sterol delta 8-isomerase and other lanosterol-converting enzymes by tamoxifen. Mol Cells 8(2) 233-239... [Pg.109]

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],... [Pg.1019]

Fig. 5.1.2 Cholesterol biosynthesis branch of the isoprenoid biosynthetic pathway. Enzymes are numbered as follows 1 squalene synthase 2 squalene epoxidase 3 2,3-oxidosqua-lene sterol cyclase 4 sterol A24-reductase (desmosterolosis) 5 sterol C-14 demethylase 6 sterol A14-reductase (hydrops-ectopic calcification-moth-eaten, HEM, dysplasia) 7 sterol C-4 demethylase complex (including a 3/ -hydroxysteroid dehydrogenase defective in congenital hemidyspla-sia with ichthyosiform nevus and limb defects, CHILD, syndrome) 8 sterol A8-A7 isomerase (Conradi-Hunermann syndrome CDPX2) 9 sterol A5-desaturase (lathosterolosis) 10 sterol A7-reductase (Smith-Lemli-Opitz syndrome). Enzyme deficiencies are indicated by solid bars across the arrows... Fig. 5.1.2 Cholesterol biosynthesis branch of the isoprenoid biosynthetic pathway. Enzymes are numbered as follows 1 squalene synthase 2 squalene epoxidase 3 2,3-oxidosqua-lene sterol cyclase 4 sterol A24-reductase (desmosterolosis) 5 sterol C-14 demethylase 6 sterol A14-reductase (hydrops-ectopic calcification-moth-eaten, HEM, dysplasia) 7 sterol C-4 demethylase complex (including a 3/ -hydroxysteroid dehydrogenase defective in congenital hemidyspla-sia with ichthyosiform nevus and limb defects, CHILD, syndrome) 8 sterol A8-A7 isomerase (Conradi-Hunermann syndrome CDPX2) 9 sterol A5-desaturase (lathosterolosis) 10 sterol A7-reductase (Smith-Lemli-Opitz syndrome). Enzyme deficiencies are indicated by solid bars across the arrows...
Enzyme defect Mevalonate kinase 3/ -Hydroxy-steroid dehydrogenase 3/M Iydroxy-sterol 8- 7-isomerase 3/I-Hydroxysterol 14-reductase 3/1-1 Iydroxysterol A5-dcsaturasc 3/ -Hydroxysterol 24-reductase 3/l-Hydroxysterol 7-reductase... [Pg.488]

Moebius, F. F., Reiter, R. J., Hanner, M., Glossmann, H. High affinity of sigma rbinding sites for sterol isomerization inhibitors evidence for a pharmacological relationship with the yeast sterol C8-C7 isomerase, Brit. J. Pharmacol. 1997, 121, 1-6. [Pg.422]

One of the best therapeutic approaches may be to prevent absorption of cholesterol from the intestines by inclusion of a higher fiber content in the diet.66 Supplementation with a cholesterol-binding resin may provide additional protection. Plant sterols also interfere with cholesterol absorption. Incorporation of esters of sitostanol into margarine provides an easy method of administration. Supplemental vitamin E may also be of value.q Another effective approach is to decrease the rate of cholesterol synthesis by administration of drugs that inhibit the synthesis of cholesterol. Inhibitors of HMG-CoA reductase,s hh (e.g., vaLostatin) iso-pentenyl-PP isomerase, squalene synthase (e.g.,... [Pg.1249]

Ergosterol biosynthesis inhibitor, by inhibition of steroid reduction (sterol—A14—reductase) and isomerisation (A8 to A7—isomerase)... [Pg.762]

In Chlorella species triparanol inhibited the removal of the 14a-methyl group, the second alkylation of the side-chain, and, in one species, the A8- A7-isomerase.149 This drug and AY9944 showed a lack of specificity in Chlorella, and it may be that primitive plants like these might be valuable as test organisms to establish the activities of potential inhibitors of sterol biosynthesis. [Pg.193]

Sterol-A -isomerase deficiency, known as Conradi-HUnermann syndrome (CDPX2), is an X-linked dominant disorder. Clinical manifestations of this disorder include skeletal abnormalities, chondrodysplasia punctata, craniofacial anomalies, cataracts, and skin abnormalities. The 7-dehydrocholesterol reductase deficiency, known as Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive disorder occurring in about 1 in 20,000 births. Clinical manifestations of affected individuals include craniofacial abnormalities, microcephaly, congenital heart disease, malformation of the limbs, psychomotor retardation, cerebral maldevelopment, and urogenital anomalies. Measurement of 7-dehydrocholesterol in amniotic fluid during second trimester or in neonatal blood specimen has been useful in the identification of the disorder. The sterol-A " -reductase deficiency causes a developmental phenotype similar to SLO syndrome and is associated with accumulation of desmosterol. The inability of de novo fetal synthesis of cholesterol combined with its inadequate transport from the mother to the fetus appears... [Pg.421]

S. Y. Cho, J-H. Kim, and Y-K. Paik Cholesterol biosynthesis from lanosterol Differential inhibition of sterol A -isomerase and other lanosterol-converting enzymes by tamoxifen. Molecules and Cells 8,233 (1998). [Pg.427]

Inhibitors of sterol biosynthesis provide many, useful, broad spectrum, fungicides, and it is essential that their effectiveness is retained as long as possible. Of the two major groups of SBI fungicides, only.the morpholines, which inhibit A reductase and/or A -A isomerase depending on their... [Pg.211]


See other pages where Sterol 58-isomerase is mentioned: [Pg.99]    [Pg.310]    [Pg.312]    [Pg.313]    [Pg.315]    [Pg.315]    [Pg.613]    [Pg.613]    [Pg.147]    [Pg.213]    [Pg.436]    [Pg.188]    [Pg.110]    [Pg.105]    [Pg.84]    [Pg.110]    [Pg.76]    [Pg.64]    [Pg.315]    [Pg.316]    [Pg.316]    [Pg.421]    [Pg.199]    [Pg.204]    [Pg.133]   
See also in sourсe #XX -- [ Pg.93 ]




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