Biomaterial Database

Inhibition of adrenocortical, mitochondrial and microsomal monooxygenases by SU-10'603, a steroid 17 alpha-hydroxylase inhibitor. 1989

L B LaCagnin, and M Levitt, and J M Bergstrom, and H D Colby

Department of Pharmacology and Toxicology, Philadelphia College of Pharmacy and Science, PA 19104.

SU-10'603 is a pyridine derivative that is widely used as a steroid 17 alpha-hydroxylase inhibitor. Studies were done to evaluate its effects in vitro on several other monooxygenases in guinea pig adrenal mitochondrial and microsomal preparations. In adrenal mitochondria, SU-10'603 produced a concentration-dependent inhibition of 11 beta-hydroxylation; 50% inhibition was obtained at a concentration of approximately 0.5 mM. Its potency was similar to that of the 11 beta-hydroxylase inhibitor, metyrapone. SU-10'603 was a more potent inhibitor of cholesterol sidechain cleavage (CSC) than of 11 beta-hydroxylation; a 50% decline in CSC activity was produced by an inhibitor concentration of approximately 0.1 mM. In adrenal microsomal preparations, SU-10'603 had no effect on the rate of 21-hydroxylation of 17 alpha-hydroxyprogesterone. However, SU-10'603 was a potent inhibitor of adrenal microsomal xenobiotic metabolizing monooxygenases (benzo[a]pyrene hydroxylase, benzphetamine demethylase), effecting approximately 50% inhibition of both reactions at a concentration of 0.05 mM. The results indicate that SU-10'603 inhibits several monooxygenases in the guinea pig adrenal cortex and is thus not specific for 17 alpha-hydroxylation.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008861	Microsomes	Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)	Microsome
D008928	Mitochondria	Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)	Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D009281	Naphthalenes	Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
D010105	Oxygenases	Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.	Oxygenase
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006899	Mixed Function Oxygenases	Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.	Hydroxylase,Hydroxylases,Mixed Function Oxidase,Mixed Function Oxygenase,Monooxygenase,Monooxygenases,Mixed Function Oxidases,Function Oxidase, Mixed,Function Oxygenase, Mixed,Oxidase, Mixed Function,Oxidases, Mixed Function,Oxygenase, Mixed Function,Oxygenases, Mixed Function
D000302	Adrenal Cortex	The outer layer of the adrenal gland. It is derived from MESODERM and comprised of three zones (outer ZONA GLOMERULOSA, middle ZONA FASCICULATA, and inner ZONA RETICULARIS) with each producing various steroids preferentially, such as ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and ANDROSTENEDIONE. Adrenal cortex function is regulated by pituitary ADRENOCORTICOTROPIN.	Cortex, Adrenal
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013764	Tetrahydronaphthalenes	Partially saturated 1,2,3,4-tetrahydronaphthalene compounds.	Tetralins