Isozyme profile

Figure 10.27. Isozymes of Lactate Dehydrogenase. (A) The rat heart LDH isozyme profile changes in the course of development. The H isozyme is represented by squares and the M isozyme by circles. The negative and positive numbers denote the days before and after birth, respectively. (B) LDH isozyme content varies by tissue. [(A) After W.-H. Li, Molecular Evolution (Sinauer, 1997), p. 283 (B) After K. Urich, Comparative Animal Biochemistry (S nngQrVQrlag, 1990), p. 542.]...

Anderson, M. D., Prasad, T. K., Stewart, C. R., 1995. Changes in isozyme profiles of catalase, peroxidase, and glutathione reductase during acclimation to chilling in mesocotyls of maize seedlings. Plant Physiol. 109 1247-1257. 

Hailing Linder C, Englund UH, Narisawa S et al (2013) Isozyme profile and tissue-origin of alkaline phosphatases in mouse serum. Bone 53(2) 399 08... 

Cornish, H. H., M. L. Barth, and V. N. Dodson. 1970. Isozyme profiles and protein patterns in specific organ damage. Toxicology and Applied Pharmacology 16 411-423. 

Compared with other molecular methods, isozyme profiling can be relatively inexpensive to perform (Loureiro and Querol, 1999). Isozyme detection should be performed at various intervals during growth because the proteins being detected may or may not be expressed by the microorganism at similar times. 

JV-Acetyltransferases (NATs) catalyze the conjugation of an acetyl group from acetyl-CoA on to an amine, hydrazine or hydroxylamine moiety of an aromatic compound. NATs are involved in a variety of phase II-diug metabolizing processes. There are two isozymes NAT I and NAT II, which possess different substrate specificity profiles. The genes encoding NAT I and NAT II are both multi-allelic. Especially for NAT II, genetic polymoiphisms have been shown to result in different phenotypes (e.g., fast and slow acetylators). 

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... 

Area under the plasma concentration-time profile Chromium-51-labeled ethylenediamine-tetraacetic acid Cytochrome P450, 3A4 isozyme... 

Transon C, Leemann T, Dayer P. In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol 1996 50(3) 209-215. 

Other studies on the pure isozymes (43, 44) showed that Km and ymaI for p-nitrophenyl phosphate and Ki for inorganic phosphate are the same for the different isozymes. The isozymes also have the same ORD spectrum and pH vs. pKi profile. The isozymes showed only slight differences in their rates of dissociation and reassociation. 

After modification of lead compound 12, it was found that pyrimidines containing the 3-methylindazole heterocycle and methylated at the C-4 amino nitrogen possessed both good in vitro and cross-species pharmacokinetic profiles. The replacement of the 3,4,5-trimethoxy aniline with a 3-aminobenzenesulfonamide led to comparable potencies. However, significant inhibition (/C50 < 10 pM) was observed against a number of cytochrome (CYP) P450 isozymes, presumably resulting from... 

SA in Table II - nmoles/hr/mg protein and N.D - not detectable. Tobacco, soy cultures and barley seedlings were the best source of ALS, both in terms of specific activity and total units. The enzyme preparations from all sources were unstable in buffer solutions in spite of protective thiol agents. The inactivation of ALS in the crude extract of tobacco showed a distinct biphasic kinetics, implying the presence of at least two isozymes (unpublished observations). The presence of two ALS genes in tobacco (29) and at least three in microorganisms (18) has also been noted by other workers. ALS from barley was most amenable to purification. Table III gives a profile for the rapid purification of this enzyme with high recovery. 

If metabolism in animal models is extensive or the generated metabolite(s) is shown to have toxic effects, in vitro metabolism studies using isolated P-450 isozymes, tissue homogenates containing the microsomal fraction, hepatocytes, and liver slices are commonly conducted to determine if the extent of metabolism and the metabolite profile is similar for animals and humans. The results from these in vitro metabolism comparison studies can be used to select the animal models for definitive development studies that have similar metabolism profiles to humans. 

Pharmacokinetic and pharmacodynamic profiles of olanzapine have been extensively reviewed (114). Olanzapine does not inhibit CYP isozymes, and no clinically significant metabolic interaction was found with fluoxetine. 

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