Molecular heterogeneity, enzyme

Protein macromolecules present in biological fluids are almost invariably heterogeneous in their characteristics. They may be products of more than one gene in the population (allotypes in the case of proteins isoenzymes in the case of enzymes), or a single individual (isotypes of proteins, allelozymes of enzymes), or be subject to post-translational modification. The result of this inherent molecular heterogeneity is that different forms of the same protein may behave differently with respect to... 

To avoid high cytotoxicity and molecular heterogeneity of poly(L-lysine), molecularly homogenous lysine-rich synthetic peptides have been used for gene transfer. It is known that the active sites of enzymes, receptor ligands and antibodies usually involve about 5 to 20 amino acids. Thus, it should be possible to design small synthetic peptides to mimic the active sites of viral proteins and formulate synthetic peptide/DNA complexes that are as efficient as vimses, but do not have their limitations. The major components of a peptide-based delivery systems are ... 

Protein contaminants can occur as natural isoforms or can arise during purification. Adventitious proteolysis and cysteine oxidation are probably the most common sources of microheterogeneity that occur during isolation (Lorber et al, 1987). This has frequently motivated the inclusion of protease inhibitors and/or reducing agents in crystallization solutions, as well as during purification. In many cases modifications that produce molecular heterogeneity are reflected in enzyme activity. For... 

Modifications affecting nonprotein components of enzyme molecules may also lead to molecular heterogeneity. 

The molecular heterogeneity of ChAc from different species was further investigated by isoelectric focusing of partially purified enzyme preparations. The isoelectric focusing experiments were run (Malthe-Sorenssen and Fonnum, 1972) with a constant load of 0.5 W for the pH gradient 3-10 and 0.75 W for the pH gradient 6-9. Constant current was usually obtained after 36 h but the column was stopped after 46 h. 

Classical heterogeneous catalysts are the subject of four major chapters in the book. We elaborate in detail on our current understanding of the molecular events that underline their catalytic phenomena and attempt to deduce from these results important catalytic reactivity concepts. This detailed understanding provides a basis for the comparison of the mechanistic principles between heterogeneous, enzyme, and homogeneous organometaUic cluster catalysis. 

Rat-kidney lysosomal jS-D-glucuronidase underwent autolysis, and its pH value increased, under mild acid conditions. This finding is considered to bear on the origin of the molecular heterogeneity of the lysosomal enzyme. 

Fig. 3. Molecular heterogeneity of human PP-ribose-P amidotransferase demonstrated by gel filtration. Two milliliters of the enzyme sample were applied to an 8% agarose column equilibrated with 50 mM potassium phosphate buffer, pH 7.4 containing 5 mM MgCl2> 60 mM -mercaptoethanol, and 0.25 M sucrose. (From Holmes, et al., in press).

P-Lactamases are enzymes that hydrolyze the P-lactam ring of P-lactamantibiotics (penicillins, cephalosporins, monobactams and carbapenems). They are the most common cause of P-lactam resistance. Most enzymes use a serine residue in the active site that attacks the P-lactam-amid carbonyl group. The covalently formed acylester is then hydrolyzed to reactivate the P-lacta-mase and liberates the inactivated antibiotic. Metallo P-lactamases use Zn(II) bound water for hydrolysis of the P-lactam bond. P-Lactamases constitute a heterogeneous group of enzymes with differences in molecular structures, in substrate preferences and in the genetic localizations of the encoding gene (Table 1). 

Molecular catalysis. The term molecular catalysis is used for catalytic systems where identical molecular species are the catalytic entity, like the molybdenum complex in Figure 8.1, and also large molecules such as enzymes. Many molecular catalysts are used as homogeneous catalysts (see (5) below), but can also be used in multiphase (heterogeneous) systems, such as those involving attachment of molecular entities to polymers. 

Enzyme catalysis. Enzymes are proteins, polymers of amino acids, which catalyze reactions in living organisms-biochemical and biological reactions. The systems involved may be colloidal-that is, between homogeneous and heterogeneous. Some enzymes are very specific in catalyzing a particular reaction (e.g., the enzyme sucrase catalyzes the inversion of sucrose). Enzyme catalysis is usually molecular catalysis. Since enzyme catalysis is involved in many biochemical reactions, we treat it separately in Chapter 10. 

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