Sep 10, 1976

Association of the Ah locus with specific changes in metyrapone and ethylisocyanide binding to mouse liver microsomes

The Journal of Biological Chemistry
G F KahlD W Nebert

Abstract

The genetic trait of "responsiveness," which refers to the capacity for induction of cytochrome P-448 and numerous monooxygenase activities by certain aromatic hydrocarbons, is known to segregate almost exclusively as a single autosomal dominant gene among progeny of appropriate crosses originating from the responsive C57BL/6 and the nonresponsive DBA/2 inbred mouse strains. In this report the allele for responsiveness is shown to be associated with (a) increases in the apparent KS values for metyrapone bound to reduced P-450; (b) increases in the ethylisocyanide difference ratio (deltaA455-490/deltaA430-490);(c) increases in the deltaA455-490 per mg of microsomal protein but not in the deltaA430-490 per mg of protein from the reduced P-450-ethylisocyanide complex; (d) an approximately 2-nm hypsochromic shift in the spectral maximum in the 446 nm region for the reduced P-450-metyrapone complex; (e) an approximately 2-nm hypsochromic shift of the absorption maximum in the 455 nm region, but not of the maximum in the 430 nm region, for the reduced P-450-ethylisocyanide complex; and (f) larger increases in the deltaA455-490 than in the deltaA430-490 per mg of microsomal protein for the reduced P450-ethylisocyanide complex as a fun...Continue Reading

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Mentioned in this Paper

Sodium Dithionite
SU 4885
Cyp2c12
Genetic Conditions, Dominant
Methylcholanthrene
Isocyanides
Cytochrome P-450 Oxygenase
Plasma Protein Binding Capacity
Microsomes, Liver
Carbon Monoxide

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