Régulation de la production d’un nucléotide triphosphate

1. Structure & Function des protéines chez les animaux Régulation de la production d’un nucléotide triphosphate Régulation allostérique Uridylate en thymidylate Cycle des Cofacteurs Deux médicaments anti-cancer Sommaire

2. dADP, dCDP, dGDP, dUDP DNA dNTP dNTP Here are the four different ribonucleoside diphosphates DNA is synthesized from deoxyribonucleoside triphosphates (dNTPs) by an enzyme, DNA polymerase, which is represented by the unlabeled green rectangle. Here are the four different ribonucleoside diphosphates Three of the deoxyribo- nucleoside diphosphates are converted to deoxyribo- nucleoside triphosphates by phosphorylation reactions. which are converted, by ribonucleotide reductase, to deoxyribonucleoside diphosphates. which are converted, by ribonucleotide reductase, to deoxyribonucleoside diphosphates. Structure & Function des protéines chez les animaux rADPrCDPrGDPrUDP ribonucleotidereductase Regulation allostérique Étape suivante Inhibition allostérique Sujet suivant Recommencer Sujet précédent This completes the allosteric regulation section. Note that ribonucleotide reductase catalyzes the committed step that inexorably leads to the dNTPs and DNA synthesis. Hence, ribonucleotide reductase is allosterically regulated to control the flow through the pathway and hence the rate of production of the dNTPs. Click again to move on to the next step, uridylate to thymidylate. Faire un essai Tutoriale Aide Son :oui/non Contenu Index Quitter Ribonucleotide reductase controls the production of deoxynucleoside tri-phosphates in the body. Enzymes are represented as green rectangles. Here are the four different ribonucleoside diphosphates This 2-enzyme pathway is regulated by negative feedback. When the dNTP concentration rises, some of the dNTP bind to to ribonucleotide reductase molecules and decrease their activity by allosteric inhibition. The thymidine triphosphate (TTP) pathway provides an important example of the regulation of enzyme activity in the body. The purpose of this pathway is the synthesis of DNA. Ribonucleotide reductase controls the production of deoxynucleoside tri-phosphates in the body. The purpose of this pathway is the synthesis of DNA. The purpose of this pathway is the synthesis of DNA. Ribonucleotide reductase controls the production of deoxynucleoside tri-phosphates in the body. Enzymes are represented as green rectangles. DNA is synthesized from deoxyribonucleoside triphosphates (dNTPs) by an enzyme, DNA polymerase, which is represented by the unlabeled green rectangle. DNA is synthesized from deoxyribonucleoside triphosphates (dNTPs) by an enzyme, DNA polymerase, which is represented by the unlabeled green rectangle. Three of the deoxyribo- nucleoside diphosphates are converted to deoxyribo- nucleoside triphosphates by phosphorylation reactions. which are converted, by ribonucleotide reductase, to deoxyribonucleoside diphosphates.

3. dADP, dCDP, dGDP, dUDP DNA dNTP dNTP Here are the four different ribonucleoside diphosphates DNA is synthesized from deoxyribonucleoside triphosphates (dNTPs) by an enzyme, DNA polymerase, which is represented by the unlabeled green rectangle. Here are the four different ribonucleoside diphosphates Three of the deoxyribo- nucleoside diphosphates are converted to deoxyribo- nucleoside triphosphates by phosphorylation reactions. which are converted, by ribonucleotide reductase, to deoxyribonucleoside diphosphates. which are converted, by ribonucleotide reductase, to deoxyribonucleoside diphosphates. Structure & Function des protéines chez les animaux rADPrCDPrGDPrUDP ribonucleotidereductase Regulation allostérique Étape suivante Inhibition allostérique Sujet suivant Recommencer Sujet précédent This completes the allosteric regulation section. Note that ribonucleotide reductase catalyzes the committed step that inexorably leads to the dNTPs and DNA synthesis. Hence, ribonucleotide reductase is allosterically regulated to control the the rate of pr flow through the pathwaé and hence oduction of the dNTPs. Click again to move on to the next step, uridylate to thymidylate. Faire un essai Tutoriale Aide Son :oui/non Contenu Index Quitter Ribonucleotide reductase controls the production of deoxynucleoside tri-phosphates in the body. Enzymes are represented as green rectangles. Here are the four different ribonucleoside diphosphates This 2-enzyme pathway is regulated by negative feedback. When the dNTP concentration rises, some of the dNTP bind to to ribonucleotide reductase molecules and decrease their activity by allosteric inhibition. The thymidine triphosphate (TTP) pathway provides an important example of the regulation of enzyme activity in the body. The purpose of this pathway is the synthesis of DNA. Ribonucleotide reductase controls the production of deoxynucleoside tri-phosphates in the body. The purpose of this pathway is the synthesis of DNA. The purpose of this pathway is the synthesis of DNA. Ribonucleotide reductase controls the production of deoxynucleoside tri-phosphates in the body. Enzymes are represented as green rectangles. DNA is synthesized from deoxyribonucleoside triphosphates (dNTPs) by an enzyme, DNA polymerase, which is represented by the unlabeled green rectangle. DNA is synthesized from deoxyribonucleoside triphosphates (dNTPs) by an enzyme, DNA polymerase, which is represented by the unlabeled green rectangle. Three of the deoxyribo- nucleoside diphosphates are converted to deoxyribo- nucleoside triphosphates by phosphorylation reactions. which are converted, by ribonucleotide reductase, to deoxyribonucleoside diphosphates.

4. dADP, dCDP, dGDP, dUDP DNA dNTP dNTP thymidylatesynthase dTDP dTMP Uridylate requires the addition of a methyl group, to make thymidylate, for DNA synthesis. The first step is dephosphorylation to deoxyuridine monophosphate. The methyl group is added by thymidylate synthase, which converts dUMP to thymidine monophosphate (dTMP). Structure & Function des protéines chez les animaux rADPrCDPrGDPrUDP ribonucleotidereductase Uridylate en thymidylate Étape suivante allostericfeedback Sujet suivant Recommencer Hit P to go back Sujet précédent dUMP Faire un essai Tutoriale Aide This completes the uridylate to thymidylate section. Note that thymidylate synthase is essential to make dTTP and hence DNA. Click again to move on to the next section, cofactor cycling. Son :oui/non Contenu Index Quitter Here is the negative feedback loop regulating the production of deoxyribonucleoside tri- phosphates. Uridylate requires the addition of a methyl group, to make thymidylate, for DNA synthesis. The first step is dephosphorylation to deoxyuridine monophosphate. The methyl group is added by thymidylate synthase, which converts dUMP to thymidine monophosphate (dTMP). Two phosphorylation events convert dTMP to thymidine triphosphate, dTTP, ready for DNA synthesis. The methyl group is added by thymidylate synthase, which converts dUMP to thymidine monophosphate (dTMP) DNA synthesis requires all four deoxyribonucleoside tri- phosphates, so dTTP is essential for DNA synthesis to proceed. Two phosphorylation events convert dTMP to thymidine triphosphate, dTTP, ready for DNA synthesis.

5. dADP, dCDP, dGDP, dUDP DNA dNTP dNTP dTDP dTMP dihydrofolate Thymidylate synthase adds a methyl group to dUMP. The methyl group comes from the cofactor, methylene tetrahydrofolate, which is converted to dihydrofolate. Structure & Function des protéines chez les animaux rADPrCDPrGDPrUDP This completes the cofactor cycling section. The cofactor, methylene tetrahydrofolate, donates a methyl group to dUMP. The resulting dihydrofolate is recycled. The recycling starts with the reaction catalyzed by dihydrofolate reductase. ribonucleotidereductase Cycle des cofacteurs Étape suivante allostericfeedback Sujet suivant methylenetetrahydrofolate Recommencer Sujet précédent dUMP Faire un essai Tutoriale thymidylatesynthase thymidylatesynthase thymidylatesynthase tetra-hydrofolate Aide Son :oui/non Contenu dihydrofolatereductase Index Quitter The most important enzyme for normal regulation of production of deoxynucleoside tri-phosphates in the body is ribonucleotide reductase. Thymidylate synthase activity is essential for DNA synthesis. Thymidylate synthase adds a methyl group to dUMP. The methyl group comes from the cofactor, methylene tetrahydrofolate, Dihydrofolate is recycled back to methylene tetrahydrofolate. The thymidine triphosphate (TTP) pathway provides an important example of the regulation of enzyme activity in the body. Enzymes are represented as green rectangles. Thymidylate synthase activity is essential for DNA synthesis. The most important enzyme for normal regulation of production of deoxynucleoside tri-phosphates in the body is ribonucleotide reductase. Thymidylate synthase activity is essential for DNA synthesis. Dihydrofolate reductase catalyzes the first step in recycling. which is converted to dihydrofolate.

6. dADP, dCDP, dGDP, dUDP DNA dNTP dNTP dTDP dTMP dihydrofolate Structure & Function des protéines chez les animaux rADPrCDPrGDPrUDP ribonucleotidereductase DNA synthesis is essential for cell proliferation. Thus, fluorouracil and methotrexate, in preventing DNA synthesis, inhibit cell proliferation. This prevents tumors from growing, but also interferes with those normal cells that need to proliferate, producing side-effects. Deux médicaments anti-cancer Étape suivante allostericfeedback Sujet suivant methylenetetrahydrofolate Recommencer Sujet précédent dUMP Faire un essai fluorodeoxy-uridylate Tutoriale thymidylatesynthase thymidylatesynthase thymidylatesynthase tetra-hydrofolate Aide methotrexate Son :oui/non Contenu dihydrofolatereductase Index Quitter Fluorodeoxyuridylate is a suicide inhibitor of thymidylate synthase. Fluorodeoxyuridylate is formed in the cell from the drug, fluorouracil. Thymidylate synthase and dihydrofolate reductase are the most important targets for anti-cancer therapy, in this pathway. Fluorodeoxyuridylate is a suicide inhibitor of thymidylate synthase. Fluorodeoxyuridylate is formed in the cell from the drug, uracil. Methotrexate is a competitive inhibitor of dihydrofolate reductase (DHFR). Either fluorouracil or methotrexate has the effect of blocking the conversion of dUMP to dTMP, thus preventing DNA synthesis. Methotrexate is a competitive inhibitor of dihydrofolate reductase (DHFR).

7. dADP, dCDP, dGDP, dUDP DNA dNTP dNTP dTDP dTMP dihydrofolate Structure & Function des protéines chez les animaux rADPrCDPrGDPrUDP ribonucleotidereductase Sommaire Étape suivante allostericfeedback Sujet suivant methylenetetrahydrofolate Recommencer Sujet précédent dUMP Faire un essai fluorodeoxy-uridylate Tutoriale thymidylatesynthase thymidylatesynthase thymidylatesynthase tetra-hydrofolate Aide methotrexate Son :oui/non Contenu dihydrofolatereductase Index Quitter Which enzyme regulates the rate of production of deoxy- ribonucleoside triphosphates? How does thymidine phosphate differ from uridine phosphate? This is the end of this module. (Hint: click on the questions at the left to hear the answer. Click the “Take a test” button, above, for more questions.)

8. Structure & Function des protéines chez les animaux Aide Étape suivante Sujet suivant • Click the right mouse button to make this presentation fit on your screen. • Click the left mouse button to move through this presentation; click the right mouse button for more options. • The screen buttons with white lettering are functional. • This presentation is a supplement to Lecture 7, “Metabolic Pathways and Feedback Mechanisms” and assumes you have the basic knowledge of the structure of nucleotides that is provided in that lecture. Recommencer Sujet précédent Faire un essai Tutoriale Aide Son :oui/non Contenu Index Quitter