Catalytic metabolisms

The proteinoid microsphere (7) possesses a sufficient number of properties to permit its study in this context as a model for a primitive cell. In the case of the microsphere, the proteinoid material is itself catalytic. Metabolism is a functional expression of molecular structures, enzyme protein. This emphasis on polymers is clearest in the context of origins. The ways in which particulate structures, i.e., cells, contribute to and control such expression can be studied uniquely in the cell model. 

Docking calculations followed by MM/MD and Monte Carlo simulations on the catalytic metabolism of the insecticide carbofiiran by... 

When tested under identical conditions, some synthetic antioxidants are more potent than tocopherol. For example, the approximate EDso for amylhydroquinone is 0.5, for methylene blue 0.3, and for DPPD (N,N -diphenyl-p-phenylenediamine) 0.03 ixg (Schwarz and Lee, 1961). We have postulated since 1956 that tocopherol may be converted into an active form before exerting its catalytic metabolic effect (Rodnan et al., 1956). In this regard it is noteworthy that a synthetic preparation of an a-tocoph-... 

Fig. 4 Catalytic metabolism of BZDO. BZDR benzoate dioxygenase reductase. (Lipscomb et al. 2002)...

Kinetics is the branch of science concerned with the rates of chemical reactions. The study of enzyme kinetics addresses the biological roles of enzymatic catalysts and how they accomplish their remarkable feats. In enzyme kinetics, we seek to determine the maximum reaction velocity that the enzyme can attain and its binding affinities for substrates and inhibitors. Coupled with studies on the structure and chemistry of the enzyme, analysis of the enzymatic rate under different reaction conditions yields insights regarding the enzyme s mechanism of catalytic action. Such information is essential to an overall understanding of metabolism. 

The metabolic breakdown of triacylglycerols begins with their hydrolysis to yield glycerol plus fatty acids. The reaction is catalyzed by a lipase, whose mechanism of action is shown in Figure 29.2. The active site of the enzyme contains a catalytic triad of aspartic acid, histidine, and serine residues, which act cooperatively to provide the necessary acid and base catalysis for the individual steps. Hydrolysis is accomplished by two sequential nucleophilic acyl substitution reactions, one that covalently binds an acyl group to the side chain -OH of a serine residue on the enzyme and a second that frees the fatty acid from the enzyme. 

The metabolic control is exercised on certain key regulatory enzymes of a pathway called allosteric enzymes. These are enzymes whose catalytic activity is modulated through non-covalent binding of a specific metabolite at a site on the protein other than the catalytic site. Such enzymes may be allosterically inhibited by ATP or allosterically activated by ATP (some by ADP and/or AMP). 

Protein kinase A (PKA) is a cyclic AMP-dependent protein kinase, a member of a family of protein kinases that are activated by binding of cAMP to their two regulatory subunits, which results in the release of two active catalytic subunits. Targets of PKA include L-type calcium channels (the relevant subunit and site of phosphorylation is still uncertain), phospholam-ban (the regulator of the sarcoplasmic calcium ATPase, SERCA) and key enzymes of glucose and lipid metabolism. 

Some enzymes require cofactors to activate catalysis. Typical cofactors are metal atoms, ammonia, and small organic molecules that associate with the enzyme and help to structure the catalytic site. To conduct an enz5anatic reaction, the necessary cofactors must be suppUed along with the substrate and the enzyme. In cell metabolism, a variety of these cofactors act in conjunction with inhibitors to control the metabolic rate. 

Apart from their catalytic function, at least one form of glutathione-5-trans-ferases has the function of simply binding xenobiotics and transporting them, without metabolism. In effect, this is an example of storage (see Section 2.3.3). The form in question is termed ligandin, and binding is associated with one particular subunit. Binding is not associated with catalytic activity. 

The catalytic capacity of the rate-fimiting reaction in a metabolic pathway is the product of the concentration of enzyme molecules and their intrinsic catalytic efficiency. It therefore follows that catalytic capacity can be... 

Pyridoxal phosphate is a coenzyme for many enzymes involved in amino acid metabolism, especially in transamination and decarboxylation. It is also the cofactor of glycogen phosphorylase, where the phosphate group is catalytically important. In addition, vitamin Bg is important in steroid hormone action where it removes the hormone-receptor complex from DNA binding, terminating the action of the hormones. In vitamin Bg deficiency, this results in increased sensitivity to the actions of low concentrations of estrogens, androgens, cortisol, and vitamin D. 

---