Name: atcase feedback inhibition in pyrimidine synthesis
Uploaded: 2023-04-30T10:13:14.000Z
Duration: 1 min 19 s
Channel: JoVE

K12 Standards

Tennessee Academic Standards

High School

Biology

from-molecules-to-organisms-structures-and-processes

From Molecules to Organisms: Structures and Processes

BIO1.LS1.3

Allosteric Proteins-ATCase

Les protéines qui contiennent des sites de liaison liés sont appelées protéines allostériques et peuvent être de différents types, tels que des enzymes, des récepteurs, des protéines structurelles et des protéines motrices. 
Par exemple, l’aspartate transcarbamoylase, également connue sous le nom d’ATCase, est une grande enzyme contenant six sous-unités catalytiques, chacune avec un site de liaison au substrat. Il possède également six sous-unités régulatrices supplémentaires, chacune avec un site capable de se lier à la fois aux pyrimidines et aux purines, les éléments constitutifs de l’ADN et de l’ARN.
L’enzyme catalyse une étape essentielle de la synthèse de la pyrimidine, la condensation de l’aspartate et du phosphate de carbamoyle pour produire de l’aspartate de carbamoyle. La vitesse de cette réaction augmente en fonction de la concentration.
La liaison de l’ATP, une purine, à l’enzyme active l’enzyme. Alors que la liaison simultanée de l’UTP et de la CTP, les pyrimidines, entraîne une inhibition de 95 % de l’activité enzymatique. 
Ce mécanisme de régulation est essentiel pour maintenir la bonne quantité de pyrimidines par rapport aux purines dans la cellule.

<ol>
	<li>Suplatov, D. et Švedas, V. (2015). Etude des sites fonctionnels et allostériques dans les superfamilles de protéines. Acta naturae, 7(4), 34-45.</li>
	<li>Bellelli, A. et Carey, J. (2017). Protéines avec plusieurs sites de liden. Dans Reversible Ligand Binding (éd. A. Bellelli et J. Carey). doi :10.1002/9781119238508.ch4</li>
	<li>Helmstaedt, K., Krappmann, S. et Braus, G. H. (2001). Régulation allostérique de l’activité catalytique : Escherichia coli aspartate transcarbamoylase versus chorismate mutase de levure. Revues de microbiologie et de biologie moléculaire : MMBR, 65(3), 404-421. doi :10.1128/MMBR.65.3.404-421.2001</li>
</ol>

protéines allostériques-atcase

Les liaisons entre sites de liaison peuvent réguler la fonction d’une protéine. Par exemple, l’activité enzymatique est souvent régulée par un mécanisme de rétroaction dans lequel le produit final du processus biochimique sert d’inhibiteur.

L'aspartate transcarbamoylase (ATCase) est une enzyme cytosolique qui catalyse la condensation du L-aspartate et du carbamoyl phosphate en N-carbamoyl-L-aspartate. Cette réaction est la première étape de la biosynthèse de la pyrimidine. L'UTP et le CTP, les produits finaux de la voie de synthèse de la pyrimidine, inhibent l'activité de l'ATCase, l'enzyme qui catalyse la première étape essentielle de cette voie. La liaison de l'UTP et du CTP à l'enzyme régule négativement le site catalytique lié lorsque la concentration de pyrimidines est élevée par rapport à la concentration de purines dans la cellule. Ce phénomène est connu sous le nom de rétro-inhibition et est essentiel au maintien des quantités adéquates de métabolites dans un organisme.

L'ATCase fait partie du complexe multi-enzymatique CAD, qui fait partie de la voie de biosynthèse de la pyrimidine, avec la carbamoyl phosphate synthétase II et la dihydroorotase. Les pyrimidines sont essentielles à la synthèse de l'ADN lors de la division cellulaire, par conséquent, l'inhibition de l'activité de l'ATCase ralentit la croissance tumorale dans le cancer.

Protéines allostériques-ATCase

Les liaisons entre les sites de liaison peuvent réguler la fonction d'une protéine. Par exemple, l'activité enzymatique est souvent régulée par un mécanisme de rétroaction où le ...

Education

Enseignement

JoVE Core

Molecular Biology

Biologie moléculaire

Unit 1

Unité 1

Protein Function

Fonction des protéines

KEY TERMS AND CONCEPTS

TERMES ET CONCEPTS CLÉS

atcase feedback inhibition in pyrimidine synthesis

ATCase is a key enzyme in pyrimidine synthesis. It is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to form N-carbamoyl-L-aspartate. This reaction starts the pathway that makes pyrimidines.

ATCase is regulated by feedback inhibition. The end products UTP and CTP bind to the enzyme and reduce its activity when pyrimidine levels are high compared with purines in the cell. This binding at one site affects the linked catalytic site, which helps keep metabolite levels balanced.

ATCase also works as part of the CAD multi-enzyme complex. CAD includes carbamoyl phosphate synthetase II and dihydroorotase in the pyrimidine biosynthesis pathway. Because pyrimidines are needed for DNA synthesis during cell division, blocking ATCase activity can slow tumor growth in cancer.

ATCase Feedback Inhibition in Pyrimidine Synthesis

atcase-feedback-inhibition-pyrimidine-synthesis

ligand binding sites

How Ligands Attach to Proteins

Ligands attach to proteins at specific binding sites on the protein surface. These sites let proteins interact with other molecules or ions and help them carry out important cell functions. Although many possible ligands may be nearby, only a matching ligand can bind to a given protein. A ligand-binding site has a shape and chemical pattern that fit its ligand. This fit comes from the protein’s amino acid chain, which gives the site its structure and reactivity. The ligand stays in place...

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the equilibrium binding constant and binding strength

the-equilibrium-binding-constant-and-binding-strength

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cofactors and coenzymes

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allosteric regulation

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Allosteric Switching in Multimeric Proteins

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gtpases and their regulation

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protein complexes with interchangeable parts

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structural protein function

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allosteric proteins-atcase

ATCase is a key enzyme in pyrimidine synthesis. It is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to form N-carbamoyl-L-aspartate. This reaction starts the pathway that makes pyrimidines. ATCase is regulated by feedback inhibition. The end products UTP and CTP bind to the enzyme and reduce its activity when pyrimidine levels are high compared with purines in the cell. This binding at one site affects the linked catalytic site, which helps keep...

key terms and concepts

Learn how ATCase is controlled by feedback inhibition from UTP and CTP and how this step helps regulate pyrimidine synthesis and DNA production.

ATCase Feedback Inhibition in Pyrimidine Synthesis | JoVE K12

molecular biology

JoVE Core Biologie Moléculaire illustre les processus moléculaires au sein de la cellule grâce à des leçons vidéos claires et concises. Les applications de ces concepts sont ensuite démontrées grâce à des expériences concrètes en laboratoire.

Arizona Science Standards

Life Science

HS+B.L1

HS+B.L1U1.5

Characteristics of Life

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Compare and contrast existing models, identify patterns, and use structural and functional evidence to analyze the characteristics of life. Engage in argument about the designation of viruses as non-living based on these characteristics.
EXPLANATION: Students begin to develop patterns of living and non-living organisms in kindergarten and build on detailed characteristics of different classifications of living organisms throughout elementary and middle school. Biology 1 discussions introduce viral particles and viral cycles, building on student understanding of living organisms to engage in an argument regarding the classification of a viral particle as either living or non-living.

BIO1.LS1.1

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BIO1.LS1.2

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Replication in Eukaryotes

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MicroRNAs

siRNA - Small Interfering RNAs

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Antibody Structure

Phosphorylation

Ligand Binding Sites

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Protein Kinases and Phosphatases

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Covalently Linked Protein Regulators

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ATCase Feedback Inhibition in Pyrimidine Synthesis

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