Answer to Question #300552 in Biochemistry for Susie

Question

Gerhart and Pardee measured ATCase activity in the presence of a variety of purine and pyrimidine derivatives. Their results are presented in Table 16.2. What compound(s) were the most effective inhibitors? activators? Explain the significance of the metabolites that served as inhibitors or activators in the context of the biosynthetic pathway presented in Figure 16.1.

Table 16.2: Effect of nitrogen bases, nucleosides and nucleotides on ATCase activity. *Indicates stimulation. (Based on Gerhart and Pardee, 1962.)

Compound

Inhibition, % (Conc = 2 mM)

Cytosine

0

Cytidine

24

CMP

38

dCMP

48

CTP

86

dCTP

88

UTP

8

GTP

35

dGTP

31

ATP

-180*

dATP

-162*

Answer 1

CTP. The enzyme catalyzes the condensation of carbamoyl phosphate and aspartate to form carbamoyl aspartate. The reaction pathway is shown in Figure 16.1. The enzyme has been fairly well characterized. It is known to consist of six regulatory subunits and six catalytic subunits. In this case, we examine the properties of ATCase isolated from E. coli to illustrate some of the important regulatory properties of multi-subunit enzymes. As an early enzyme in a multi-step pathway, the ATCase reaction is a logical one to regulate the synthesis of pyrimidine nucleotides. Both purine nucleotides and pyrimidine nucleotides are needed in roughly equal amounts as substrates for DNA synthesis in rapidly dividing cells. The regulation of the ATCase enzyme ensures a proper balance of purine and pyrimidine pools in E. coli.