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The characterization of the flavin-containing monooxygenase gene family of man

Janmohamed, Azara; (1998) The characterization of the flavin-containing monooxygenase gene family of man. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Flavin-containing monooxygenases (FMO) are a family of enzymes that metabolise a variety of foreign compounds such as pesticides, pharmaceuticals and toxicants. They are found in most tissues of all mammals. Five FMO isoforms (FMO1, 2, 3, 4 and 5) have been identified. Analysis of human genomic DNA by Southern blot hybridization with cDNAs encoding the different FMO isoforms gave simple patterns of hybridization suggesting that a single gene encodes each protein. Northern blot hybridization analyses and RNase protection assays showed that each FMO has a distinct tissue specific pattern of expression. This pattern differs between man and other species. The skin is a major portal of entry for a variety of chemicals and environmental pollutants. FMOs 1, 3 and 5 were found to be the major forms present in human skin. In situ hybridization demonstrated that FMOs 1, 3, 4 and 5 are expressed in the sebaceous gland and the epidermis. Western blotting analysis of FMOs in whole skin homogenates and microsomes was unsuccessful due to a high degree of cross-reactivity of the polyclonal antibodies used with other skin proteins. The methimazole assay was used to determine the presence of FMO activity in skin. The expression of FMOs in an immortalised human keratinocyte (HaCaT) cell line was also studied. These cells could offer an alternative system for biotransformation studies; this is possible only if HaCaT cells express a similar range of FMOs as the skin or primary human keratinocyte cultures. Primary cultures of human keratinocytes expressed FMOs 1, 2, and 3 to varying degrees, whereas HaCaT cells, expressed only FMOs 1, 4 and 5. An analysis of cytochromes P450 in whole human skin, primary keratinocyte cultures and HaCaT cells was undertaken. Regional localisation of CYP2As, CYP2B6 and CYP3As in the skin was the same as for FMOs.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The characterization of the flavin-containing monooxygenase gene family of man
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Flavin-containing monooxygenases
URI: https://discovery.ucl.ac.uk/id/eprint/10106727
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