Monkey, cytochrome

In the Cynomolgus monkey, cytochrome P450, NADPH-cytochrome P450 reductase and some monooxygenase activities, especially ethoxycouma-rin 0-deethylase activity, were present in respiratory epithelium, although in lower levels than in liver (Longo et al. 1992). 

Abdelgadir SE, Roselli CE, Choate JV, Resko JA. 1997. Distribution of aromatase cytochrome P450 messenger ribonucleic acid in adult rhesus monkey brains. Biol Reprod 57 ... 

ScaUet AC, Muskhelishvili L, Slikker W Jr, Kadlubar FF. 2005. Sex differences in cytochrome P450 IBl, an estrogen-metabolizing enzyme, in the rhesus monkey telencephalon. J Chem Neuroanat 29 71-80. 

Dalet-Beluche 1, Boulenc X, Eabre G, Maurel P, Bonfils C (1992) Purification of two cytochrome P450 isozymes related to CYP2A and CYP3A gene families from monkey (baboon, Papio papio) liver microsomes. Cross reactivity with human forms. Eur J Biochem 204 641-648 Damaj Ml, Siu EC, Sellers EM, Tyndale RE, Martin BR (2007) Inhibition of nicotine metabolism by methoxysalen Pharmacokinetic and pharmacological studies in mice. J Pharmacol Exp Ther 320 250-257... 

Ohmori S, Shirakawa C, Motohashi K, Yoshida H, Abe H, Nakamura T, Horie T, Kitagawa H, Asaoka K, Rikihisa T, et al (1993a) Purihcahon from hver microsomes from untreated cynomolgus monkeys of cytochrome P450 closely related to human cytochrome P450 2B6. Mol Pharmacol 43 183-190... 

Ohmori S, Horie T, Guengerich FP, Kiuchi M, Kitada M (1993b) Purification and characterization of two forms of hepatic microsomal cytochrome P450 from untreated cynomolgus monkeys. Arch Biochem Biophys 305 405 13... 

Drug interactions No drug interaction studies have been conducted with Avonex. Other interferons have been found to reduce cytochrome P-450-mediated drug metabolism. Hepatic microsomes isolated from Avonex-treated rhesus monkeys showed no influence on hepatic P-450 enzyme metabolism activity. 

The first transient expression system for cytochrome P450 expression was the COS cell system which couples monkey cells with an SV40-based expression vector (Zuber et al., 1986). The cDNA of interest is introduced into a plasmid expression vector under control of a heterologous promoter. The vector is introduced into COS cells via electroporation or another method allowing DNA uptake. The plasmid vector replicates within the cells and cDNA-derived protein accumulates within the cell. 

With regard to drug interactions, it is important to note that the cytochrome P-450 system is not involved in the metabolism of moxifloxacin. In vitro studies using cytochrome P-450 enzymes have shown that moxifloxacin does not inhibit the enzymes CYP 1A2, CYP 3A4, CYP 2C9, CYP 2C19, and CYP 2D6. Moxifloxa-cin s metabolic profile makes it highly unlikely that it will alter the pharmocoki-netics of drugs affected by these enzymes. In rhesus monkeys, oxidative phase I biotransformations do play an additional role, however [272,273]. 

Schmucker DL, Wang RK. Effects of aging on the properties of rhesus monkey liver microsomal NADPH-cytochrome c (P-450) reductase. Drug Metab Dispos 1987 15 225-32. 

Polymeric mixtures were prepared from horse, human, rabbit, monkey (Macaco mulatto), turkey, tuna, cow, and kangaroo (Macropus canguru) cytochromes c at protein to glutaraldehyde molar ratios of 1 11. All yielded similar gel filtration elution patterns. 

Studies have been conducted in animals to attempt to clarify the role of varying rates of drug metabolism in humans and animals and the likelihood for development of addiction/dependence to narcotics. Hydromorphone has been studied in several animal models because it is metabolized in humans by specific cytochrome P450 isoenzymes. So far, studies have looked at administration of agents that either block or promote P450 isoenzymes responsible for hydrocodone metabolism and the impact of enhanced or degraded metabolism of hydrocodone on those animal models. Results in rats and rhesus monkeys have demonstrated little effect from modifying hydrocodone metabolism. 

A second example of in vivo activation of drug metabolism was recently reported by Wei Tang and his associates (83). The in vitro addition of quinidine to monkey liver microsomes or hepatocytes stimulated the cytochrome P450 3A4-mediated metabolism of diclofenac to 5-hydroxydiclofenac (83). Although quinidine had little or no effect on the Km for diclofenac metabolism by monkey... 

Otton, S.V. Tyndale, R.F. Wu, D. Inaba, T. Kalow, W. and Sellers, E.M. Catalytic and immunologic similarities between monkey and human liver c54ochrome P-450dbl (human cytochrome P450 2D6). DrugMetab Dispos 20(1) 1-5, 1992. 

In agreement with what has been observed in animals, the level of aldehyde oxidase activity present in human liver is also markedly dependent on the substrate employed, the analytical method used to evaluate the substrate, and most importantly, the intrinsic activity of the preparation (Beedham et al. 1992). For N-1-methylnicotinamide oxidase activity, the rank order was cynomolgus monkey > rat > beagle dog > human liver (Rodrigues 1994). The relative levels of aldehyde oxidase activity may help determine the relative extent of lactim formation from N-heterocyclic compounds such as N-1-methylnicotinamide. Of course, formation of lactim metabolites from iminium ions can also be coordinately regulated by other enzyme activities including cytochromes P-450. Thus, formation of... 

Matsunaga T, Iwawaki Y, Watanabe K, Yamamoto I, Kageyama T, Yoshimura H (1995) Metabolism of delta-9-tetrahydrocannabinol by cytochrome P450 isozymes purified from hepatic microsomes of monkeys. Life Sci 56 2089-2095... 

We find also some interesting results from the data shown in Table 3.4. Comparing the amino acid sequence of cytochrome c from N. winogradskyi with those of cytochromes c from human, monkey, and tuna, the numbers of the different amino acids at the corresponding positions of the sequence are found to be 62, 61, and 59, respectively. The number of different amino acids in the sequence is 72 between yeast and the bacterial cytochrome c. From these data, the evolutionary distance between yeast and the bacterium is farther than that between the animals and the bacterium. The number of different amino acids in the sequence of cytochrome c is 44 between human and yeast cytochromes c. By simple analysis of the figures, we are led to a conclusion that the bacterium has appeared on Earth evolutionarily after human or that yeast has appeared after human. This is a mystery of molecular evolution that needs to be solved in future studies. 

Ronk M, Shively JE, Shute EA, Blake RC Jr (1991) Amino acid sequence of the blue copper protein rusticyanin from Thiobacillus ferrooxidans. Biochemistry 30 9435-9442 Rothfus JA, Smith EL (1965) Amino acid sequence of rhesus monkey heart cytochrome c. J Biol Chem 240 4277-4283... 

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