Cholinesterases multiple forms

Many iso-enzymes are hybrids of a limited number of sub-units. Some enzymes show multiple forms owing to increasing levels of polymerization of a single sub-unit these should not really be called iso-enzymes, because they do not have any genetic difference between the different forms. Cholinesterase, for instance, shows five forms consisting of a single sub-unit existing as monomers, dimers, trimers, tetramers and pentamers. 

Many differences in overall toxicity between males and females of various species are known (Table 9.1). Although it is not always known whether metabolism is the only or even the most important factor, such differences may be due to gender-related differences in metabolism. Hexobarbital is metabolized faster by male rats thus female rats have longer sleeping times. Parathion is activated to the cholinesterase inhibitor paraoxon more rapidly in female than in male rats, and thus is more toxic to females. Presumably many of the gender-related differences, as with the developmental differences, are related to quantitative or qualitative differences in the isozymes of the xenobiotic-metabolizing enzymes that exist in multiple forms, but this aspect has not been investigated extensively. 

Aggregation of enzyme molecules with each other or with nonenzymatic proteins may give rise to multiple forms that can be separated by techniques that depend on differences in molecular size. For example, four catalytically active cholinesterase components with molecular weights ranging from about 80,000 to 340,000 are found in most sera, with the heaviest component, C4, contributing most of the enzyme activity. Other enzyme forms are also occasionally present, but it appears that the principal serum cholinesterase fractions can be attributed to different states of aggregation of a single monomer. 

The genes at the Eg locus, which affect the isozyme pattern of the enzyme, are called Eg for the more common variant, and Ej for the less common variant. Various means of designating the multiple forms of cholinesterase, which can be characterized from their electrophoretic properties, are considered in Section 2.6. 

Most workers have adopted the international convention on nomenclature of multiple forms of enzymes (12), so that the major isoenzymes of cholinesterase are numbered consecutively, with the form having the highest mobility towards the anode being designated one. Unfortunately, there are two sets of symbols for the electrophoretic bands of the enzyme, namely C1-C4 (H6) and ChEj-ChEs e.T (L8). It turns out that C1-C3 are identical to ChEj-ChEs, respectively, but C4 is identified with ChE4 +... 

L12. LaMotta, R. V., Woronick, C. L., and Reinfrank, R. F., Multiple forms of serum cholinesterase Molecular weights of the isoenzymes. Arch. Biochem. Biophys. 136, 448-451 (1970). 

Unakami, S., S. Suzuki, E. Nakanishi, K. Ichinohe, M. Hirata, and Y. Tanimoto. 1987. Comparative studies on multiple forms of serum cholinesterase in various species. Experimental Animals 36 199-204. 

Brodbeck, U., Gentinetta, R., and Lundin, S. J., 1973, Multiple forms of a cholinesterase from body muscle of plaice (Pleuronectes platessa) and possible role of sialic acid in cholinesterase reaction specificity, A era Chem. Scand. 27 561. 

Cholinesterases are subdivided into acetylcholinesterase and cholinesterase, one with a narrow, the other with broad substrate specificity [109-112], Both enzymes exist in multiple molecular forms distinguishable by their subunits association (Fig. 2.4). The hydrodynamic properties of these associations have allowed globular (G) and asymmetric (A) forms to be distinguished. The G forms can be hydrophilic (water-soluble, and excreted into body fluids) or amphiphilic (membrane-bound). The homomeric class exists... 

Figure 1 Subunit structure of the multiple molecular forms of ChEs. G, globular forms A, asymmetric forms with collagen-like tails. Each circle is a catalytic subunit disulfide bridges indicated by S-S as found in the electric organ of the electric eel. (Modified from Brimijoin WS (1992) US EPA Workshop on Cholinesterase Methodologies.)...

Modern techniques for protein separation have been used to demonstrate the existence of multiple molecular forms of cholinesterase. Such entities, which are groups of isoenzymes, can be separated either by electrophoresis or by chromatography (H8) moreover, they can be distinguished by kinetic means (e.g., R3). 

Multiple Molecular Forms of Human Plasma Cholinesterase... 

The classic view of two cholinesterases whose sole function is to terminate cholinergic signals at the synapse has been repeatedly challenged by observations that were incongruent with this view and suggested a far more complex picture of multiple molecular forms with distinct temporal and spatial expression patterns. This complexity mainly results from alternative splicing... 

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