The Isoforms

Most NOS inhibitors are stmcturaHy related to L-arginine and do not differentiate between the isoforms (Table 15). t - / 7-Methy1 arginine (l-NMA) (264) is a competitive inhibitor and also irreversibly inhibits NOS. T.-/ 7-Nitroarginine (l-NNA) (265), L-AP -nitroarginine methyl ester (t.-NAMF) (266),... 

Heterogeneity. Natural aequorin is not a homogeneous protein it is a mixture of many isoforms having isoelectric points ranging from 4.2 to 4.9 (Blinks and Harrer, 1975). The isoform composition may vary to some extent by the purification method employed, due to uneven loss of isoforms during purification. Consequently, the properties of each preparation of aequorin may also vary. By anion-exchange... 

HPLC, about one dozen of the isoforms, aequorins A, B, C, -J, were isolated (Shimomura, 1986a Shimomura et al., 1990). An example of HPLC separation of isoforms is shown in Fig. 4.1.6, and a comparison of the properties of the isoforms is given in Table 4.1.2. 

Table 4.1.2 Properties of the Isoforms of Aequorin (Shimomura, 1986a)... 

Fig. 9.12 An example of HPLC separation of the isoforms of Mycena citricolor luciferin precursors. The sample adsorbed on a PRP-lcolumn was eluted by a linear increase of acetonitrile from 20% to 40% in a pH 7.5 buffer containing 5 mM tributylamine sulfate. Practically all the peaks have the precursor activity.

Human umbilical vein endothelial cells (HUVEC) express the isoforms ECE-la, -lb, -Id and ECE-2. In these cells, ET-1 is secreted via both a constitutive and a regulated pathway. The ratio of released ET-1 big-ET-1 is 4 1. About 80% of the ET-1 is secreted at the abluminal cell surface of endothelial cells. ECE-isoforms are abundantly expressed on the cell surface of endothelial cells and to a lower level also on vascular smooth muscle cells. In atherosclerotic lesions of vessels, however, ECE expression in smooth muscle cells is upregulated. ECE isoforms expressed in smooth muscle cells contribute significantly to the generation of mature ET in normal and in particular atherosclerotic vessels. 

The insulin-binding domain of the INSR is located within a cystein-rich region of the a-subunits. Alternative splicing of exon 11 generates two isoforms of the a-subunit which differ in their C-terminus and in their tissue distribution (type A leukocytes type B liver type A and B skeletal muscle and fat). The isoforms differ in their affinity to insulin (A > B), but then-relevance for normal and impaired insulin action is not entirely clear [1,2]. 

Na+/Ca2+ Exchangers. Figure 4 Molecular properties of drugs interacting with NCX. Scheme summarizing the potency, the mode of selectivity, the molecular site of action and the isoform specificity of drugs interfering with NCX activity. 

All class I PI3Ks are heterodimeric enzymes composed of a 110 kDa catalytic subunit (with the isoforms pi 10 a,(3,5 or y) that associates with a regulatory subunit. Although the class I PI3Ks are capable of phosphorylating Ptdlns, PtdIns(4)P and PtdIns(4,5)P2 in vitro, it appears that they only use PtdIns(4,5)P2 as a substrate in vivo. Receptor-induced formation of Ptdlns... 

CD45RO Known to be the isoform of leukosialin present on memory T cells CD46 Known to be z membrane cofactor protein... 

Cytochrome P450 (EC 1.14.14.1) enzymes are well known for their ability to metabolize the majority of drugs, to detoxify environmental pollutants, and to activate some classes of carcinogens [93]. The most highly expressed subfamily is CYP 3A, which includes the isoforms CYP 3A4, CYP 3A5, CYP 3A7, and CYP 3A43 [93, 94]. The most abundant isoform is CYP 3A4, which corresponds to 30% of the total P450 content in the liver and about 70% of the total P450 content in the... 

The cellular and subcellular distributions of a-subunit isoforms provide clues to their different physiological functions. The four isoforms exhibit about 85% sequence identity. The most substantial differences occur in their N-terminal regions and in an 11-residue sequence of the large cytoplasmic loop. When measured in cell cultures, the isoforms differ in their apparent affinities for intracellular Na+ (al < a2 < a3) [21 ] and extracellular K+ (a3 < a2 = al) [22], In adult tissues, al is the major iso form in... 

There are multiple isoforms of the a and p subunits of soluble GC that exhibit distinct tissue and cellular distributions. Most of the isoforms are expressed in brain, including 0Ci 3 and and P3. The p2 subunit is found primarily in lung. This isoform also contains a consensus sequence at its carboxy terminus for isoprenylation or carboxymethyl-ation, which could serve to anchor the protein to the plasma membrane. It has been proposed that specific isoforms of the a and P subunits of GC may form heterodimers with distinct functional and regulatory properties, although this remains to be established with certainty. 

Human ERa has 565 amino acids, greater therefore than the dominant isoform of ER/J, which has 530 amino acids (Kuiper et al. 1996), the isoforms are products of the same gene and are generated by alternate processing of mRNA. Nevertheless, the structure in the domains of both types of ER reflect the general pattern described, except that ER/3 lacks the carboxyterminal F region (Kumar et al. 1987 Nilsson et al. 2001). Both ERa and ERj0, as well... 

Ji, F., Kanbara, N., and Obata, K. (1999) GABA and histogenesis in fetal and neonatal mouse brain lacking both the isoforms of glutamic acid decarboxylase. Neurosci. Res. 33, 187-194. 

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