(ASKING FOR QUESTION NUMBER 4.) Background Aspartate transcarbamoylase (ATCase)
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(ASKING FOR QUESTION NUMBER 4.)
Background Aspartate
transcarbamoylase (ATCase) catalyzes an early step in the synthesis of the pyrimidine nucleotides UTP and 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. The goal in this case was to identify the cellular metabolites that serve as activators and inhibitors of ATCase.
1.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.
2. The kinetics of the ATCase reaction were examined using increasing concentrations of aspartate, in the presence and absence of CTP and ATP as shown in Figure 16.2.
a. What information can you obtain by looking at the shapes of the curves in this figure?
b. What kinetic parameter(s) change in the presence of CTP? What parameter(s) do not change? What is the significance of these observations?
c. Answer question 2b for ATP.
figure 16.2 and 16.3
Figure 16.3: Percent ATCase activity in the presence of CTP, and in the presence of both CTP and ATP (based on Gerhart and Pardee, 1962).
3. The investigators examined the behavior of the ATCase enzyme in the presence of CTP, and in the presence of both CTP and ATP. The concentration of CTP is 0.1 mM and the concentration of ATP is 2 mM. The results are shown in Figure 16.3. What is the significance of these observations?
Question 4. Back in 1962, Gerhart and Pardee developed a model for the regulation of the activity of the ATCase enzyme by CTP and ATP, using the pathway given in Figure 16.1. Describe that model, using information presented here as well as what you have learned about allosteric enzymes. Be sure to include a sentence explaining the physiological significance of your model.
HCO3 Glutamine ATP ATCase Carbamoyl phosphate Aspartate N-carbamoylasparitate UMP UTP Figure 16.1: Pyrimidine synthetic pathway. CTPExplanation / Answer
Question 4. ANS:
John Gerhart and Arthur Pardee elaborated this model they both concluded that ATCase (aspartate transcarbamoylase) enzyme activity is could be regulated with CTP and ATP.
This model is a good example of an allosteric regulation, in which the enzyme ATCase is allosterically inhibited by its own end product CTP.
In the presence of low CTP concentration the ATCase catalyzed reaction can occurs more quickly. When the levels of CTP concentration is high, the rate of the reaction gradually becomes slow.
ATCase catalytic activity is increased by ATP, Which is the end product of purine synthesis pathway. ATCase can condenses L-aspertate and carbomoyl phosphate into N-carbamyl-L-aspertate.
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