Search

Your search keyword '"Henderson, Marilyn C."' showing total 34 results
Start Over Author "Henderson, Marilyn C."
34 results on '"Henderson, Marilyn C."'

10. Human Microdosing with Carcinogenic Polycyclic Aromatic Hydrocarbons: In Vivo Pharmacokinetics of Dibenzo[def,p]chrysene and Metabolites by UPLC Accelerator Mass Spectrometry

Author

Madeen, Erin P., primary, Ognibene, Ted J., additional, Corley, Richard A., additional, McQuistan, Tammie J., additional, Henderson, Marilyn C., additional, Baird, William M., additional, Bench, Graham, additional, Turteltaub, Ken W., additional, and Williams, David E., additional

Published
2016
Full Text
View/download PDF

24. Identification and functional analysis of common human flavin-containing monooxygenase 3 genetic variants.

Author

Koukouritaki, Sevasti B, Poch, Mark T, Henderson, Marilyn C, Siddens, Lisbeth K, Krueger, Sharon K, Vandyke, Jonathan E, Williams, David E, Pajewski, Nicholas M, Wang, Tao, and Hines, Ronald N

Abstract

Flavin-containing monooxygenases (FMOs) are important for the disposition of many therapeutics, environmental toxicants, and nutrients. FMO3, the major adult hepatic FMO enzyme, exhibits significant interindividual variation. Eighteen FMO3 single-nucleotide polymorphism (SNP) frequencies were determined in 202 Hispanics (Mexican descent), 201 African Americans, and 200 non-Latino whites. Using expressed recombinant enzyme with methimazole, trimethylamine, sulindac, and ethylenethiourea, the novel structural variants FMO3 E24D and K416N were shown to cause modest changes in catalytic efficiency, whereas a third novel variant, FMO3 N61K, was essentially devoid of activity. The latter variant was present at an allelic frequency of 5.2% in non-Latino whites and 3.5% in African Americans, but it was absent in Hispanics. Inferring haplotypes using PHASE, version 2.1, the greatest haplotype diversity was observed in African Americans followed by non-Latino whites and Hispanics. Haplotype 2A and 2B, consisting of a hypermorphic promoter SNP cluster (-2650C>G, -2543T>A, and -2177G>C) in linkage with synonymous structural variants was inferred at a frequency of 27% in the Hispanic population, but only 5% in non-Latino whites and African Americans. This same promoter SNP cluster in linkage with one or more hypomorphic structural variant also was inferred in multiple haplotypes at a total frequency of 5.6% in the African-American study group but less than 1% in the other two groups. The sum frequencies of the hypomorphic haplotypes H3 [15,167G>A (E158K)], H5B [-2650C>G, 15,167G>A (E158K), 21,375C>T (N285N), 21,443A>G (E308G)], and H6 [15,167G>A (E158K), 21,375C>T (N285N)] was 28% in Hispanics, 23% in non-Latino whites, and 24% in African Americans.

Published
2007
Full Text
View/download PDF

30. Assessment of methyl p-tolyl sulfoxidation by human FMO2.1, p.S195L and p.N413K flavin-containing monooxygenase variant.

Author

Krueger, Sharon K., Henderson, Marilyn C., Siddens, Lisbeth K., VanDyke, Jonathan E., Fumes, Bjarte, Schlenk, Daniel, and Williams, David E.

Subjects
*MONOOXYGENASES, *FLAVINS, *MEMBRANE proteins, *PHYSIOLOGICAL oxidation, *PHYSIOLOGICAL effects of magnesium, *GENETIC mutation
Abstract

Previous work identified two common ethnically-dependent allelic variants of human flavin-containing monooxygenase 2 (FMO2) that encode protein with monooxygenase activity that could occur in combination with the functional FM02*1 allele (Q472 protein); the encoded proteins were S195L and N413K. To understand how these variants alter enzyme activity, we performed assays with the FMO substrate, methyl p-tolyl sulfide (MTS) under a range of conditions with S195L, N413K and Q472 produced by over-expression in Sf9 insect cells. MTS sulfoxidation was assayed by HPLC. All protein variants demonstrated the same pattern of response to the presence of magnesium (increased activity) and to heat (decreased activity). Increased activity was observed with Q472 and N413K in response to increasing pH and to cholate, while S195L had diminished activity. The major effect of the N413K substitution was to increase velocity compared with Q472, while S195L had reduced activity and altered patterns of response to incubation conditions. In contrast to Q472 and N413K, S195L activity was negligible unless NADPH was added before MTS. Also, the K,, for S195L is at least 10-fold higher than for Q472 and N413K. Although these allelic variants are expected to occur infrequently as mutations to the FM02*1 allele, they contribute to our overall understanding of mammalian FMO structure and function. [ABSTRACT FROM AUTHOR]

Published
2007

Catalog

Books, media, physical & digital resources
See catalog results