Isoform pattern

Figure 3. PME isoform patterns in cell wall extracts fiom active and resting cells, a cell wall extracts from successive segments (A, B, C and D) sectioned along mui bean hypocotyb and exhibiting decreasing elongation rates a, and y m c the main PME isoforms present in the extracts, tteir pi are respectively around 7.5, S.5 and above 9.1. b cell wall extracts obtained from poplar cambium and inner bark tissues during cambial active (may) and rest (december and march) periods 1, 2 and 3 represent the activity of 3 groups of PME isoforms with pi around 5-6, 7.5 and above 9.1. Activities expressed as percent of total PME activity present in each extract.

Fig. 3. Diagram of the isoelectric focusing patterns of the six common apolipoprotein E phenotypes. E, Protein e, apoE allele. Top Focusing position of the three common apoE isoforms, designated E2, E3, and E4, as they appear in the three homozygous and three heterozygous phenotypes. Bottom Effect of posttranslational sialylation on the isoform patterns. Sialylated derivatives are indicated as E,.

Utermann was the first to recognize that a particular isoform pattern is associated with type III hyperlipoproteinemia (Utermann et ai, 1975), indicating that apoE polymorphism was associated with this disorder. Later, with the introduction of the three-allele model by Zannis and Breslow (1980), it was shown that type III hyperlipoproteinemia was associated with the E2/2 phenotype. The underlying basis for this association is discussed in Section IVA. 

In severe neonatal nemaline myopathy virtually every muscle fiber shows multiple rods and all muscle fiber types are affected. However in juvenile cases, two different patterns of fiber type involvement are seen. In one there is a clear size difference between type 1 fibers, which are abnormally small (hypotrophic or atrophic) and which contain numerous nemaline rods, and type 2 fibers, which are either of normal diameter or hypertrophic and contain few, if any, nemaline rods. Other patients show a gross predominance of type 1 muscle fibers, again with rods virtually confined to this fiber type. These findings may be explicable in terms of the involvement of isoforms of a-actinin specific to slow and fast muscle fiber types. 

Phytoestrogens may elicit their biological effects by binding to estrogen receptors (ERs). Until recently, only a single ER isoform, ERa, had been identified however, a second receptor termed ERp has also been identified (Enmark et al, 1997, 1999 Saunders et al, 2000, 2001). It has been shown that the ERs have different intracellular and tissue distribution patterns and are responsible for different biological effects (see Table 5.1). A number of spliced variants of both ERa and ERp have also been identified (Inoue et al, 2000 Ogawa et al, 1998 Vladusic et al, 1998). 

In most plant materials that have been examined, several PME isoforms have been extracted fixDm the cell walls. What is their reqjective fimction How is their synthesis regulated -Immunolocalisation experiments have shown that some Golgi vesicles can be labelled with the JIM 5 antibody, which is known to recognize low-ester pectins [19]. This raises the question of the action pattern of the pectin methyltransferases. Can they produce pectins with different... 

All cell-wall extracts contained several PME isoforms differing in their isoelectric points. The isoenzyme patterns changed significantly during cell ageing. 

Evidence that BPH could be hormone related came from studies of a population of pseudohermaphrodites in the Dominican Republic. These individuals are genetically male, but do not display normal male genitalia until the onset of puberty. They are therefore raised as females until puberty. Studies revealed that these pseudohermaphrodites are deficient in an isoform of the enzyme steroid 5a-reductase, which is responsible for catalyzing the conversion of testosterone to dihydrotestosterone (DHT). In addition to the overt sexual manifestations of this condition, affected individuals show no incident of male pattern baldness, mild or no acne, and underdevelopment of the prostate. These observations led researchers to postulate that a selective inhibitor of steroid 5a-reductase would be an effective treatment for BPH. 

Finasteride has been clinically proved to reduce the median volume of the prostate in patients and is currently prescribed for the treatment of BPH. The compound also has demonstrated efficacy in the treatment of male pattern baldness and is prescribed for this indication as well. Subsequent to the discovery of finasteride, it was found that there are two isoforms of steroid 5a-reductase in mammals, type 1 and type 2. The type 2 isoform is primarily active in reproductive tissue, while the type 1 isoform contributes to DHT formation in the skin, liver, and reproductive tissue. Finasteride inhibits both isozymes in rats, but selectively inhibits the type 2 isozyme only in humans. It is hypothesized that dual inhibition of both isoforms of steroid 5a-reductase might prove more effective in treating BPH. Hence the GlaxoSmithKline group identified and developed dutasteride (Figure 8.18C). Dutasteride inactivates both human isoforms of steroid 5a-reductase by a mechanism similar to that described for finasteride (Bramson et al., 1997 see also the Web site www.avodart.com). Both finasteride and dutasteride have demonstrated clinical efficacy and are currently used in the treatment of BPH. 

Protein phosphatase 1. Four subtypes of PP1, derived from three genes, are known. These enzymes, listed in Table 23-2, are highly homologous and exhibit similar substrate specificities therefore, they can be considered isoforms. However, the proteins exhibit very distinct patterns of distribution in the brain. PP1 dephosphorylates a wide array of substrate proteins. Its catalytic subunit can form complexes with over 50 regulatory subunits in a... 

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