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Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Estabrook, Cooper, and Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of defensive compounds, fatty acids, and hormones.
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the CYP2D6 gene. CYP2D6 is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.
Cytochrome P450 2E1 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals.
Cytochrome P450 2A6 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. CYP2A6 is the primary enzyme responsible for the oxidation of nicotine and cotinine. It is also involved in the metabolism of several pharmaceuticals, carcinogens, and a number of coumarin-type alkaloids. CYP2A6 is the only enzyme in the human body that appreciably catalyzes the 7-hydroxylation of coumarin, such that the formation of the product of this reaction, 7-hydroxycoumarin, is used as a probe for CYP2A6 activity.
Deltamethrin is a pyrethroid ester insecticide. Deltamethrin plays a key role in controlling malaria vectors, and is used in the manufacture of long-lasting insecticidal mosquito nets; however, resistance of mosquitos and bed bugs to deltamethrin has seen a widespread increase.
The Anopheles gambiae complex consists of at least seven morphologically indistinguishable species of mosquitoes in the genus Anopheles. The complex was recognised in the 1960s and includes the most important vectors of malaria in sub-Saharan Africa, particularly of the most dangerous malaria parasite, Plasmodium falciparum. It is one of the most efficient malaria vectors known. The An. gambiae mosquito additionally transmits Wuchereria bancrofti which causes lymphatic filariasis, a symptom of which is elephantiasis.
Cytochrome P450 1A2, a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene.
Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. The enzyme catalyzes sequential hydroxylations of the steroid angular methyl group at C18 after initial 11β-hydroxylation. It is encoded by the CYP11B2 gene in humans.
Cytochrome P450 17A1 is an enzyme of the hydroxylase type that in humans is encoded by the CYP17A1 gene on chromosome 10. It is ubiquitously expressed in many tissues and cell types, including the zona reticularis and zona fasciculata of the adrenal cortex as well as gonadal tissues. It has both 17α-hydroxylase and 17,20-lyase activities, and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. More specifically, the enzyme acts upon pregnenolone and progesterone to add a hydroxyl (-OH) group at carbon 17 position (C17) of the steroid D ring, or acts upon 17α-hydroxyprogesterone and 17α-hydroxypregnenolone to split the side-chain off the steroid nucleus.
Steroid 21-hydroxylase is an enzyme that hydroxylates steroids at the C21 position and is involved in biosynthesis of aldosterone and cortisol. The enzyme converts progesterone and 17α-hydroxyprogesterone into 11-deoxycorticosterone and 11-deoxycortisol, respectively, within metabolic pathways that ultimately lead to aldosterone and cortisol. Deficiency in the enzyme may cause congenital adrenal hyperplasia.
Steroid 11β-hydroxylase, also known as steroid 11β-monooxygenase, is a steroid hydroxylase found in the zona glomerulosa and zona fasciculata of the adrenal cortex. Named officially the cytochrome P450 11B1, mitochondrial, it is a protein that in humans is encoded by the CYP11B1 gene. The enzyme is involved in the biosynthesis of adrenal corticosteroids by catalyzing the addition of hydroxyl groups during oxidation reactions.
Cytochrome P450 3A43 is a protein that in humans is encoded by the CYP3A43 gene.
Cytochrome P450 4F12 is a protein that in humans is encoded by the CYP4F12 gene.
CYP2R1 is cytochrome P450 2R1, an enzyme which is the principal vitamin D 25-hydroxylase. In humans it is encoded by the CYP2R1 gene located on chromosome 11p15.2. It is expressed in the endoplasmic reticulum in liver, where it performs the first step in the activation of vitamin D by catalyzing the formation of 25-hydroxyvitamin D.
CYP20A1 is a protein which in humans is encoded by the CYP20A1 gene.
CYP4F22 is a protein that in humans is encoded by the CYP4F22 gene.
CYP2A7 is a protein that in humans is encoded by the CYP2A7 gene.
Attractive toxic sugar baits or ATSBs are oral insecticides designed to reduce malaria infections by killing the host vector - the mosquito - rather than the parasite itself.
Thioester containing protein 1, often called TEP1 is a key component of the arthropod innate immune system. TEP1 was first identified as a key immunity gene in 2001 through functional studies on Anopheles gambiae mosquitoes.
Cytochrome P450, family 9, also known as CYP9, is a cytochrome P450 family found in Insect genome, CYP9 and insect CYP6 family belong to the same clan as mammalian CYP3 and CYP5 families. The first gene identified in this family is the CYP9A1 from the Heliothis virescens, which is involved in thiodicarb insecticide resistance. Subfamily CYP9A in Lepidopteran play important roles in insecticide resistance, can metabolize esfenvalerate efficiently.
References
- ↑ Djouaka, RF; Bakare, AA; Coulibaly, ON; Akogbeto, MC; Ranson, H; Hemingway, J; Strode, C (13 November 2008). "Expression of the cytochrome P450s, CYP6P3 and CYP6M2 are significantly elevated in multiple pyrethroid resistant populations of Anopheles gambiae s.s. from Southern Benin and Nigeria". BMC Genomics. 9: 538. doi:10.1186/1471-2164-9-538. PMC 2588609 . PMID 19014539.
- ↑ Ismail HM, O'Neill PM, Hong DW, Finn RD, Henderson CJ, Wright AT, et al. (December 2013). "Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions". Proceedings of the National Academy of Sciences of the United States of America. 110 (49): 19766–71. Bibcode:2013PNAS..11019766I. doi: 10.1073/pnas.1320185110 . PMC 3856776 . PMID 24248381.
- ↑ Wagah, MG; Korlević, P; Clarkson, C; Miles, A; Anopheles gambiae 1000 Genomes, Consortium.; Lawniczak, MKN; Makunin, A (25 May 2021). "Genetic variation at the Cyp6m2 putative insecticide resistance locus in Anopheles gambiae and Anopheles coluzzii". Malaria Journal. 20 (1): 234. doi:10.1186/s12936-021-03757-4. PMC 8146665 . PMID 34034756.
