Isozymic

Compounds having the 16,17 ketal, eg, budesonide, amcinonide, fluocinonide, halcinonide, triamcinolone acetonide, and flurandrenohde, also undergo metabohsm by routes that parahel that of cortisol metabohsm. Unsymmetrical acetals such as budesonide are also metabolized by routes not available to the more metabohcahy stable symmetrical 16a,17a-isopropyhdiene-dioxysubstituted compounds (desonide, flunisohde, and triamcinolone acetonide). Isozymes within the cytochrome P450 3A subfamily are thought to catalyze the metabohsm of budesonide, resulting in formation of 16a-hydroxyprednisolone and 6P-hydroxybudesonide (19,20) (Fig. 3) in addition to the more common metabohc steps (oxidation via reduction of A, etc). 

In addition, vinpocetine selectively inhibits a specific calcium, calmodulin-dependent cycHc nucleotide phosphodiesterase (PDF) isozyme (16). As a result of this inhibition, cycHc guanosine 5 -monophosphate (GMP) levels increase. Relaxation of smooth muscle seems to be dependent on the activation of cychc GMP-dependent protein kinase (17), thus this property may account for the vasodilator activity of vinpocetine. A review of the pharmacology of vinpocetine is available (18). 

The hver microsomal dmg-metabolizing system is of particular importance. This oxidative pathway is mediated by isozymes of the cytochrome family (Fig. 4). At least ten enzyme families exist to accommodate the abiUty of humans to handle many foreign molecules (21). 

Testosterone, the principal male sex steroid hormone, is synthesized in five steps from cholesterol, as shown below. In the last step, five isozymes catalyze the 17/3-hydroxysteroid dehydrogenase reactions that interconvert 4-androstenedione and testosterone. Defects in the synthesis or action of testosterone can impair the development of the male phenotype during embryogenesis and cause the disorders of human sexuality termed male pseudohermaphroditism. Specifically, mutations in isozyme 3 of the 17/3-hydroxysteroid dehydrogenase in the fetal testis impair the for-... 

Specialized controls Enzyme regulation is an important matter to cells, and evolution has provided a variety of additional options, including zymogens, isozymes, and modulator proteins. 

Muscle cells contain two different isozymes of creatine kinase, one in the mitochondria and one in the sarcoplasm. Explain. 

The enzymes of the glyoxylate cycle in plants are contained in glyoxysomes, organelles devoted to this cycle. Yeast and algae carry out the glyoxylate cycle in the cytoplasm. The enzymes common to both the TCA and glyoxylate pathways exist as isozymes, with spatially and functionally distinct enzymes operating independently in the two cycles. 

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). 

Blanco G et al (1998) Isozymes of the Na+-K+-ATPase heterogeneity in structure, diversity in function. Am J Physiol 275(5 Part 2) F633-F650... 

The two isozymes are both homodimers, composed of approximately 600 amino acids and possess approximately 60% homology. The three-dimensional structures of COX-1 and COX-2 are very similar. Each one consists of three independent units an epidermal growth factor-like domain, a membrane-binding section and an enzymic domain. The catalytic sites and the residues immediately adjacent are identical but for two small but crucial variations that result in an increase in the volume of the COX-2-active site, enabling it to accept inhibitor-molecules larger than those that could be accommodated in the COX-1 molecule. 

Forskolin is a diteipene derivative from the plant Coleus forskohlii. It activates all mammalian isozymes of adenylyl cyclase except AC9 and AC 10. 

This kinase specifically phosphorylates the regulatory light chain of myosin after activation by calcium-calmodulin. Several isozymes of approximately 135 kDa exist. 

Endothelial NO Synthase (eNOS) expression is relatively specific for endothelial cells. However, the isozyme has also been detected in certain neurons of the brain, in syncytiotrophoblasts of human placenta and in LLC-PKi kidney tubular epithelial cells. 

Cytochrome P450 (CYP) Cytochrome P450 isozymes Cytochrome P450 mono-oxygenases Mixed function oxidases... 

CYP2J2 is abundant in cardiovascular tissue and active in the metabolism of arachidonic acid to eicosanoids that possess potent anti-inflammatory, vaso-dilatory, and fibrinolytic properties. Polymorphic alleles with reduced function are known. Some other CYP2 subfamilies and isozymes listed in Table 1 are still not well characterized, in part because most of them were discovered in the course of the human genome project. 

CYP26 consists of three enzymes each representing a separate subfamily (Table 1) probably are all involved in retinoic acid hydroxylation. CYP26A1 is an all trans retinoic acid hydroxylase which degrades retinoic acid, an important signalling molecule for vertebrate development. It acts through retinoic acid receptors. The other CYP26 isozymes are also retinoic acid hydroxylases. 

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