Cytochrome p450 steroid hormone biosynthesis

CYP1A1 also metabolizes polyunsaturated fatty acids into signaling molecules that have physiological as well as pathological activities. CYP1A1 has monoxygenase activity in that it metabolizes arachidonic acid to 19-hydroxyeicosatetraenoic acid (19-HETE) (see 20-Hydroxyeicosatetraenoic acid ) but also has epoxygenase activity in that it metabolizes docosahexaenoic acid to epoxides , primarily 19 R ,20 S -epoxyeicosapentaenoic acid and 19 S ,20 R -epoxyeicosapentaenoic acid isomers (termed 19,20-EDP) and similarly metabolizes eicosapentaenoic acid to epoxides, primarily 17 R ,18 S -eicosatetraenic acid and 17 S ,18 R -eicosatetraenic acid isomers (termed 17,18-EEQ). [12] Synthesis of 12(S)-HETE by CYP1A1 has also been demonstrated. [13] 19-HETE is an inhibitor of 20-HETE, a broadly active signaling molecule, . it constricts arterioles , elevates blood pressure, promotes inflammation responses, and stimulates the growth of various types of tumor cells; however the in vivo ability and significance of 19-HETE in inhibiting 20-HETE has not been demonstrated (see 20-Hydroxyeicosatetraenoic acid ). The EDP (see Epoxydocosapentaenoic acid ) and EEQ (see epoxyeicosatetraenoic acid ) metabolites have a broad range of activities. In various animal models and in vitro studies on animal and human tissues, they decrease hypertension and pain perception; suppress inflammation; inhibit angiogenesis , endothelial cell migration and endothelial cell proliferation; and inhibit the growth and metastasis of human breast and prostate cancer cell lines. [14] [15] [16] [17] It is suggested that the EDP and EEQ metabolites function in humans as they do in animal models and that, as products of the omega-3 fatty acids , docosahexaenoic acid and eicosapentaenoic acid, the EDP and EEQ metabolites contribute to many of the beneficial effects attributed to dietary omega-3 fatty acids. [14] [17] [18] EDP and EEQ metabolites are short-lived, being inactivated within seconds or minutes of formation by epoxide hydrolases , particularly soluble epoxide hydrolase , and therefore act locally. CYP1A1 is one of the main extra-hepatic cytochrome P450 enzymes; it is not regarded as being a major contributor to forming the cited epoxides [17] but could act locally in certain tissues such as the intestine and in certain cancers to do so.

 suboxone
telithromycin

aprepitant
erythromycin
fluconazole
grapefruit juice
verapamil 2
diltiazem

cimetidine

amiodarone
NOT azithromycin
chloramphenicol
boceprevir
ciprofloxacin
delaviridine
diethyl-dithiocarbamate
fluvoxamine
gestodene
imatinib
mibefradil
mifepristone
norfloxacin
norfluoxetine
starfruit
telaprevir
voriconazole

Blizzard and Kyle (1963) offered the first substantial evidence for the autoimmune concept. They found antiadrenal antibodies in 36 of 71 patients with Addison disease and antithyroid antibodies in 22. Hung et al. (1963) found circulating adrenal antibodies in 2 sibs with Addison disease. A third sib had died from Addison disease. One of the affected sibs also had hypoparathyroidism, pernicious anemia, and superficial moniliasis. The authors suggested the disorder may not be inherited as a simple mendelian recessive but may be autoimmune in nature.

Cytochrome p450 steroid hormone biosynthesis

cytochrome p450 steroid hormone biosynthesis

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