4.17 : Allosteric Proteins-ATCase

Proteins that contain linked binding sites are called allosteric proteins and can be of various types, such as enzymes, receptors, structural proteins, and motor proteins.

For example, aspartate transcarbamoylase, also known as ATCase, is a large enzyme containing six catalytic subunits, each with a substrate binding site. It also has six additional regulatory subunits, each with a site that can bind both pyrimidines and purines, the building blocks of DNA and RNA.

The enzyme catalyzes an essential step in pyrimidine synthesis, the condensation of aspartate and carbamoyl phosphate to produce carbamoyl aspartate. The rate of this reaction increases in a concentration-dependent manner.

Binding of ATP, a purine, to the enzyme activates the enzyme. Whereas, the simultaneous binding of UTP and CTP, pyrimidines, results in a 95% inhibition of enzyme activity.

This regulatory mechanism is essential to maintain the right amount of pyrimidines relative to purines in the cell.

Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.

Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway, inhibit the activity of ATCase, the enzyme that catalyzes the first essential step of this pathway. Binding of UTP and CTP to the enzyme negatively regulates the linked catalytic site when the concentration of pyrimidines is high, relative to the concentration of purines in the cell. This phenomenon is known as feedback inhibition and is essential in maintaining the right amounts of metabolites in an organism.

ATCase is part of the CAD multi-enzyme complex, part of the pyrimidine biosynthesis pathway, along with carbamoyl phosphate synthetase II and dihydroorotase. Pyrimidines are essential for DNA synthesis during cell division, therefore, inhibition of ATCase activity slowing down tumor growth in cancer.

Tags

Allosteric Proteins ATCase Binding Sites Feedback Mechanism Enzyme Activity Regulation Pyrimidine Biosynthesis Aspartate Transcarbamoylase UTP CTP Feedback Inhibition CAD Multi enzyme Complex Carbamoyl Phosphate Synthetase II Dihydroorotase DNA Synthesis Cell Division Tumor Growth

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