Catalytic specificity

These appHcations are mosdy examples of homogeneous catalysis. Coordination catalysts that are attached to polymers via phosphine, siloxy, or other side chains have also shown promise. The catalytic specificity is often modified by such immobilization. Metal enzymes are, from this point of view, anchored coordination catalysts immobilized by the protein chains. Even multistep syntheses are possible using alternating catalysts along polymer chains. Other polynuclear coordination species, such as the homopoly and heteropoly ions, also have appHcations in reaction catalysis. 

Lipase is an enzyme which catalyzes the hydrolysis of fatty acid esters normally in an aqueous environment in living systems. However, hpases are sometimes stable in organic solvents and can be used as catalyst for esterifications and transesterifications. By utihzing such catalytic specificities of lipase, functional aliphatic polyesters have been synthesized by various polymerization modes. Typical reaction types of hpase-catalyzed polymerization leading to polyesters are summarized in Scheme 1. Lipase-catalyzed polymerizations also produced polycarbonates and polyphosphates. 

The catalytic specificity of the cycloamyloses has led to their utilization as a model for understanding enzymatic catalysis. It is the authors expectation that the cycloamyloses will continue to serve as an enzyme model as well as a model for designing more efficient catalytic systems. Toward this end, it would seem profitable to pursue the idea that the cycloamyloses may lower the activation energy of a chemical reaction by inducing strain into the substrate. 

We should recognize that the citric acid cycle is catalytic. Specifically, the molecule that is required to condense with acetyl-SCoA in the first step of the cycle is regenerated in the last step. In principle therefore, the cycle is capable of consuming acetyl-SCoA and producing carbon dioxide endlessly as it turns. Here is a schematic... 

Babbitt, P.C. Gerlt, J.A. (1997) Understanding enzyme super-families chemistry as the fundamental determinant in the evolution of new catalytic activities. J. Biol. Chem. 27, 30,591-30,594. An interesting description of the evolution of enzymes with different catalytic specificities, and the use of a limited repertoire of protein structural motifs. 

Flavins are very versatile redox coenzymes. Flavopro-teins are dehydrogenases, oxidases, and oxygenases that catalyze a variety of reactions on an equal variety of substrate types. Since these classes of enzymes do not consist exclusively of flavoproteins, it is difficult to define catalytic specificity for flavins. Biological electron acceptors and donors in flavin-mediated reactions can be two-electron acceptors, such as NAD+ or NADP+, or a variety of one-electron acceptor systems, such as cytochromes (Fe2+/ Fe3+) and quinones, and molecular oxygen is an electron acceptor for flavoprotein oxidases as well as the source of oxygen for oxygenases. The only obviously common aspect of flavin-dependent reactions is that all are redox reactions. 

The preparation of imprinted polymers based on imidazole was also recently reported by Li et al. [41], who used essentially the same system as Mosbach to investigate the effect of the monomer-template ratio on catalytic specificity. 

Fu H, Ebert-Khosla S, Hopwood DA, Khosla C (1994) Engineered biosynthesis of novel polyketides dissection of the catalytic specificity of the act ketoreductase. J Am Chem Soc 116 4166-4170... 

Strobel SM, Halpert JR. Reassessment of cytochrome P450 2B2 catalytic specificity and identification of four active site residues. Biochemistry 1997 36 11697-11706. 

Figure 4. Two versions of the E,-E2 model illustrating the uncertainty with respect to the orientation of cation-binding sites in E,P and E2. The orientation is indicated by a dot (pointing upwards for cytoplasmic orientation and downwards for extracytoplas-mic orientation). In A the orientation of the cation-binding site with respect to the membrane changes simultaneously with a change in catalytic specificity of the ATP-binding/phosphorylation site. In B it is the phosphorylation that determines orientation of the cation binding site.

In the absence of a-type ions from their cytoplasmic uptake sites, the pump protein displays an alternative catalytic specificity the aspartyl residue can no longer react with ATP, but it readily phosphorylates from inorganic phosphate... 

Figure 6. Time course of change in catalytic specificity (upper panel) and Ca2+ dissociation from extracytoplasmic low affinity sites (lower panel) following phosphorylation of the SR Ca2+-ATPase with ATP. The amount of ADP-insensitive phosphoen-zyme (E2P) was measured in two ways (I) [y-32P]ATP was included in the reaction mixture and the radioactivity incorporated into the enzyme was determined after acid quenching at various time intervals. To remove the ADP-sensitive phosphoenzyme so that only ADP-insensitive phosphoenzyme was measured, ADP was added 4 sec before the quench (upper panel, right scale) (2) by the enhancement of fluorescence from a trinitrophenyl-derivative of ADP bound in the catalytic site in exchange with ADP after the phosphorylation (upper panel, left scale). The change in Ca2+ binding was measured indirectly by use of murexide as an indicator of free Ca2+ in the medium. The data show that Ca2+ dissociates simultaneously with formation of E2P. The data points were taken from Andersen et al., 1985.

The concepts outlined above are tentatively summarized in the minimal reaction cycles shown in Figure 11. The cycles show not just two conformational states, but multiple states. The E1/E2 notation is used primarily to refer to distinct catalytic specificities for ATP-ADP exchange and Pi-H20 exchange, respectively. There is... 

Pollack et al, 1986 Benkovic et al., 1990 Driggers and Schultz, 1996 Xiu et al., 1996). In this sense, the catalytic space of the enzyme is the binding of the transition state similar reactions bind to similar transition states. Because catalytic specificity is never perfect, any enzyme can catalyze a range of reactions, represented by a ball in catalytic space. This indicates that only a finite number of enzymes may be necessary to cover all simple catalytic tasks. 

It, has been speculated that the catalytic specificity of an enzyme requires the active site of the enzyme and the transition state of the reaction at the substrate molecule to be structurally complementary 26). Molecules which resembled the transition state structure could thus be expected to bind the active site tightly. This concept was taken up and developed by Lienhard27) and Wolfenden 28) as transition state analogs. 

The factors to be considered in tailoring enzymes for the food industry can be divided into five areas a) sensitivity to processing conditions b) catalytic specificity or action profile c) purity d) source and e) application economics. 

Catalytic Specificity. The catalytic specificity or action profile of an enzyme is the tailoring factor that offers unlimited potential. Being able to select just the exact bond to cleave in a polymer, or to control within a very narrow range the size distribution in a polymer digest, offers enormous product quality potential. 

---