Aspartate Carbamoyltransferase

Aspartate carbamoyltransferase (also known as aspartate transcarbamoylase or ATCase) is one of the most studied enzymes for allosteric regulation. It catalyzes the reaction that follows:

> Aspartate + Carbamoyl Phosphate <=> Carbamoyl Aspartate

As seen in Figure 11.35, ATCase is at the crossroads of biosynthetic pathways that lead to proteins or pyrimidines. ATCase catalyzes the joining of aspartate and carbamoyl phosphate to form N-carbamoyl-L-aspartate, the first metabolite committed to the synthesis of pyrimidines. The enzyme is sensitive to feedback inhibition by cytidine triphosphate (CTP), one of the end products of the pathway, and is activated by ATP, a purine nucleotide (Figure 11.36). ATCase is a multisubunit protein consisting of 6 catalytic subunits and 6 regulatory subunits.The quarternary structure of ATCase enzyme is shown in Figure 11.37. A detailed representation of one catalytic subunit and one regulatory subunit is shown in Figure 11.38.

Allosteric regulation of ATCase involves changes in the quaternary structure of the molecule. A major rearrangement of subunit positions occurs in the T-> R transition.

Sometimes different organisms regulate similar pathways in different ways. For example, ATCase is the major control point in the pyrimidine pathway synthesis in bacteria, whereas eukaryotes regulate the synthesis of carbamoyl phosphate (Figure 11.35). In mammals, the carbamoyl phosphate synthetase II is inhibited by UDP, UTP, CTP, dUDP, and UDP-glucose.

See also: Regulation of Enzyme Activity, Pyrimidine Nucleotide Metabolism (from Chapter 22), Figure 22.10

INTERNET LINKS:

> 1. Properties of Allosteric Enzymes

> 2. Aspartate Transcarbamoylase (SCOP)

> 3. Image of ATCase (slow)