Isoenzymes distribution

Changes in Isoenzyme Distribution During Development and Disease... 

The patterns of several sets of isoenzymes change during normal development in tissues from many species. For example, changes in the relative proportions of several isoenzymes are noted during the embryonic development of skeletal muscle. The proportions of the electrophoretically more cathodal isoenzymes, of both LD and CK, progressively increase in this tissue, until approximately the sixth month of intrauterine life, when the pattern resembles that of differentiated muscle. Smaller quantitative changes in isoenzyme distribution may continue to birth and into early postnatal life. 

The diagnosis of organ disease is aided by measurement of a number of enzymes characteristic of that tissue or organ. Most tissues have characteristic enzyme patterns (Table 8-2) that may be reflected in the relative serum concentrations of the respective enzymes in disease. The diseased tissue can be further identified by determination of the isoenzyme pattern of one of these enzymes (e.g., lactate dehydrogenase, creatine kinase) in the serum, since many tissues have characteristic isoenzyme distribution patterns for a given enzyme. For example, creatine kinase (CK) is a dimer composed of two subunits, M (for muscle) and B (for brain), that occur in three isoenzyme forms, BB(CKi), MB(CK2) and MM(CK3), which catalyze the reversible phosphorylation of creatine with adenosine triphosphate (ATP) as the phosphate donor ... 

The most important applications of electrophoresis are in molecular biology and medicine where, for example, the study of inherent variabilities of serum proteins has produced a new branch of genetics, and the discovery of hemoglobin variants in several anemias has introduced the notion of molecular diseases. Electrophoresis has also greatly facilitated sequencing of nucleic acids, the clinical diagnosis of protein dyscrasias, the measurement of isoenzyme distribution, and the classification of lipoproteinemias, among others. 

The isoenzyme distribution patterns of LDH and aldolase in rat kidney deserve particular attention. These patterns look as if they have been formed by the superimposition of two isoenzyme distributions, one heavily weighted toward A4-LDH, the other toward B4-LDH. And, in fact, when adult kidney cortex and medulla are analyzed separately they reveal distinct patterns. Cortex contains mostly B4-LDH and medulla mostly A4-LDH (Smith and Kissane, 1963). Medulla contains only aldolase A whereas in cortex both aldolase A and B are present (Lebherz and Rutter, 1969). In chicken heart, the CPK distribution is different in atrium and ventricle, ventricle showing only BB-CPK, atrium a complement of BB-MB-, and MM-CPK (Bogenmann, 1973). It is obvious, therefore, that isoenzymes may be useful in identifying differences in... 

The discovery that MAO has two isoenzymes with different distributions, substrate specificity and inhibitor sensitivity has helped to rehabilitate the MAOIs to some extent. These isoenzymes are the products of different genes on the X-chromosome and share about 70% sequence homology. Whereas noradrenaline and 5-HT are metabolised preferentially by MAOa, tyramine and dopamine can be metabolised by either isoenzyme. Selective inhibitors of MAOa (e-g- moclobemide Da Prada et al. 1989) should therefore be safe and effective antidepressants whereas the selective MAOb inhibitor, selegiline, should not have any appreciable antidepressant activity (Table 20.5). 

The slow and fast isoenzymes of Ca -ATPase contain 42 and 50 arginine residues, respectively. The C-terminal sequence of the neonatal fast-twitch isoenzyme is Arg-Arg-Lys. There are only four arginine residues in the putative transmembrane helices, which are probably located near the cytoplasmic or luminal surface of the membrane. The remaining arginine residues are distributed in the cytoplasmic domains. 

Maly IP, Toranelli M, Sasse D. Distribution of alcohol dehydrogenase isoenzymes in the human liver acinus. Histo-chem Cell Biol 1999 111 391-397. 

Bittar, P. G., Charnay, Y., Pellerin, L. etal. Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain. /. Cereb. Blood Flow Metab. 16 1079-1089,1996. 

Aldehyde reductases are a group of isoenzymes that catalyze the NADPH-specific reduction of aldehydes. Ketones do not serve as substrates for these enzymes. The best substrates for aldehyde reductase are aromatic aldehydes and those aldehydes obtained through metabolism of biogenic amines. The species distribution, specificity, and inhibition of aldehyde reductases have been reviewed (792). 

As with the aldehyde reductases, ketone reductases are specific for NADPH as reductant. Also, some isoenzymes of ketone reductase have not been purified to homogeneity and therefore not fully characterized. It is clear, however, that the ketone reductases catalyze reduction of aromatic, aliphatic, cyclic, and unsaturated ketones to the corresponding alcohols. The ketone reductases also catalyze reduction of aromatic and aliphatic aldehydes to primary alcohols. The distribution and specificity of ketone reductases has been reviewed (103). 

Nitric oxide is widely distributed and at least three isoenzymes of nitric oxide synthase (NOS) have been described iNOS (inducible), eNOS (endothelial) and nNOS (neuronal). The substrate for NOS is the amino acid arginine ... 

The two isoenzymes of cyclooxygenase are distributed differently Macrophages contain COX-2 whereas cells in... 

Investigations into die expression of distinct PKC isoenzymes in various tissues revealed a highly variable tissue distribution. PKCa and PKCX are ubiquitously expressed. Brain contains all isoenzymes, whereas others such as skin and skeletal muscle contain only a few (Blobe et al., 1994). Such a different pattern of expression suggests Aat the PKC isoenzymes play different roles in the tissue of expression and do not suggest a general role of all isoenzymes in cell proliferation. In many publications an influence of PKC on cell proliferation has been reported. 

Tricyclics interact with other drugs and substances at a variety of points during distribution and metabolism. Most interactions occur at the CYP isoenzyme complex in the liver. Other interactions occur at peripheral sites and involve interaction at the noradernergic receptors (a and P). A summary of major TCA drug interactions is given in Table 23.2. 

The Kupffer cells are known to contain significant peroxidase activity and also acetyltransferase. The differential distribution of isoenzymes may also be a factor in the localization of damage. 

Carter, M. J. Carbonic anhydrase isoenzymes properties distribution and functional significance. BioL Rev. 47, 465 (1972)... 

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