Polymer systems enzyme modulated

UDP-Gal (Figure 6.7) [100]. This enzyme module system was further used with poly(ethylene glycol) (PEG)-polymer bound substrates that facihtate facile product isolation [99]. 

In developing such systems, we have investigated two enzyme-substrate reactions as a means of modulating polymer erosion rates ... 

In animal systems, the enzyme exists as a polyfunctional inactive protein with a MW of about 240,000 (Hardie and Cohen, 1978 Tanabe et al., 1975 MacKall and Lane, 1977), which consists of three domains—biotin carboxylase, BCCP, and transcarboxylase. These are linked by an exposed polypeptide chain peculiarly susceptible to attack by endogenous proteases. In the presence of citrate this protomer rapidly aggregates to polymers of 7-10 million daltons, and these polymers are active forms of the enzyme. These polymers rapidly depolymerize in the presence of low concentrations of palmi-toyl-CoA to the inactive protomer. In addition, there is increasing evidence that a phosphorylation-dephosphorylation cycle is involved in further modulating the activity of this important enzyme (Hardie and Cohen, 1978 Lee and Kim, 1977). 

All of these results indicate that the observed inhibition of DNA polymerase a by poly(ADP-ribosyl)ation is not due to the suppression of factors modulating the enzymatic activity but dnough the direct inhibition of DNA polymerase a-primase complex itself. Considering our previous observation (1) that the inhibited activity of DNA polymerase a by the incubation in a poly(ADP-ribosyl)ating system could be restored by a mild alkaline treatment, a procedure known to hydrolyze the ADP-ribosyl-protein liiikage (12), the observed inhibition is probably due to the modiBcation of either DNA polymerase a and/or primase subunit itself although direct evidence for covalent association of polymer to the enzyme subunit(s) remains to be proven. 

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