Structure Function des protines chez les animaux Rgulation

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

Regulation allostérique r. ADP r. CDP ribonucleotide r. GDP reductase r. UDP d. ADP, d. CDP, d. GDP, d. UDP Structure & Function des protéines chez les animaux Étape suivante Inhibition allostérique Sujet suivant Recommencer Sujet précédent DNA d. NTP This completes the allosteric regulation section. Note that ribonucleotide reductase catalyzes the committed step that inexorably leads to the d. NTPs and DNA synthesis. Hence, ribonucleotide reductase is allosterically regulated to control the flow through the pathway and hence the rate of production of the d. NTPs. Click again to move on to the next step, uridylate to thymidylate. Faire un essai Tutoriale Aide Son : oui/non Contenu Index Quitter Enzymes are represented green Here DNA are is synthesized theof four from as The Ribonucleotide The thymidine purpose triphosphate reductase thisdifferent pathway controls (TTP) is the rectangles. ribonucleoside deoxyribonucleoside diphosphates triphosphates pathway production synthesis provides of of DNA. deoxynucleoside an important triexample which arebyconverted, by. DNA (d. NTPs) enzyme, of phosphates the regulation inanthe ofbody. enzyme activity in ribonucleotide reductase, to polymerase, which is represented by the body. deoxyribonucleoside unlabeled green rectangle. diphosphates. Ribonucleotide reductase controls Here are the four different The purpose ofrepresented this pathway is the Enzymes are as green DNA is synthesized from Three of the deoxyriboproduction of deoxynucleoside triribonucleoside diphosphates synthesis of DNA. rectangles. deoxyribonucleoside triphosphates nucleoside diphosphates are phosphates in the body. which are converted, (d. NTPs) enzyme, by. DNA convertedbytoan deoxyribonucleotide reductase, to polymerase, which is represented by the nucleoside triphosphates by deoxyribonucleoside unlabeled green rectangle. phosphorylation reactions. diphosphates. Here are the deoxyribofour different This 2 -enzyme pathway is controls The Ribonucleotide purpose of this reductase pathway is the DNA is from Three ofsynthesized the ribonucleoside regulated byof negative feedback. synthesis production DNA. ofdiphosphates deoxynucleoside trideoxyribonucleoside triphosphates nucleoside diphosphates are which ared. NTP converted, by DNA When the phosphates in concentration the body. (d. NTPs) by enzyme, converted to an deoxyribonucleotide reductase, to rises, some oftriphosphates the d. NTP bind polymerase, which is represented by the nucleoside by to todeoxyribonucleoside ribonucleotide reductase unlabeled green reactions. rectangle. phosphorylation diphosphates. molecules and decrease their activity by allosteric inhibition.

Regulation allostérique r. ADP r. CDP ribonucleotide r. GDP reductase r. UDP d. ADP, d. CDP, d. GDP, d. UDP Structure & Function des protéines chez les animaux Étape suivante Inhibition allostérique Sujet suivant Recommencer Sujet précédent DNA d. NTP This completes the allosteric regulation section. Note that ribonucleotide reductase catalyzes the committed step that inexorably leads to the d. NTPs and DNA synthesis. Hence, ribonucleotide reductase is allosterically regulated to control the rate of pr flow through the pathwaé and hence oduction of the d. NTPs. Click again to move on to the next step, uridylate to thymidylate. Faire un essai Tutoriale Aide Son : oui/non Contenu Index Quitter Enzymes are represented green Here DNA are is synthesized theof four from as The Ribonucleotide The thymidine purpose triphosphate reductase thisdifferent pathway controls (TTP) is the rectangles. ribonucleoside deoxyribonucleoside diphosphates triphosphates pathway production synthesis provides of of DNA. deoxynucleoside an important triexample which arebyconverted, by. DNA (d. NTPs) enzyme, of phosphates the regulation inanthe ofbody. enzyme activity in ribonucleotide reductase, to polymerase, which is represented by the body. deoxyribonucleoside unlabeled green rectangle. diphosphates. Ribonucleotide reductase controls Here are the four different The purpose ofrepresented this pathway is the Enzymes are as green DNA is synthesized from Three of the deoxyriboproduction of deoxynucleoside triribonucleoside diphosphates synthesis of DNA. rectangles. deoxyribonucleoside triphosphates nucleoside diphosphates are phosphates in the body. which are converted, (d. NTPs) enzyme, by. DNA convertedbytoan deoxyribonucleotide reductase, to polymerase, which is represented by the nucleoside triphosphates by deoxyribonucleoside unlabeled green rectangle. phosphorylation reactions. diphosphates. Here are the deoxyribofour different This 2 -enzyme pathway is controls The Ribonucleotide purpose of this reductase pathway is the DNA is from Three ofsynthesized the ribonucleoside regulated by negative feedback. synthesis production of DNA. ofdiphosphates deoxynucleoside trideoxyribonucleoside triphosphates nucleoside diphosphates are which ared. NTP converted, by DNA When the concentration phosphates in the body. (d. NTPs) by enzyme, converted to an deoxyribonucleotide reductase, to rises, some of the d. NTP bind polymerase, which is represented by the nucleoside triphosphates by to deoxyribonucleoside to ribonucleotide reductase unlabeled green reactions. rectangle. phosphorylation diphosphates. molecules and decrease their activity by allosteric inhibition.

Uridylate en thymidylate r. ADP r. CDP ribonucleotide r. GDP reductase r. UDP d. ADP, d. CDP, d. GDP, d. UDP Structure & Function des protéines chez les animaux Étape suivante allosteric feedback Sujet suivant Hit Recommencer P to go back Sujet précédent DNA d. NTP Faire un essai d. UMP Tutoriale thymidylate synthase d. TDP d. TMP This completes the uridylate to thymidylate section. Note that thymidylate synthase is essential to make d. TTP and hence DNA. Click again to move on to the next section, cofactor cycling. Aide Son : oui/non Contenu Index Quitter Uridylate thefeedback addition Heremethyl is therequires negative The group is added by of a methyl group, make loop regulating the to production thymidylate synthase, which thymidylate, for to DNA of deoxyribonucleoside triconverts d. UMP thymidine synthesis. step is phosphates. The first monophosphate (d. TMP). dephosphorylation to deoxyuridine monophosphate. Uridylate requires addition Twomethyl phosphorylation eventsby The groupthe is added of a methyl group, to make convert d. TMP to thymidine thymidylate synthase, which thymidylate, for DNA triphosphate, d. TTP, ready for converts d. UMP to thymidine synthesis. The first step is DNA synthesis. monophosphate (d. TMP). dephosphorylation to deoxyuridine monophosphate. The DNA methyl synthesis grouprequires is added allbyfour Two phosphorylation events thymidylate deoxyribonucleoside synthase, which triconvert d. TMP to thymidine converts phosphates, d. UMP so to d. TTP thymidine is essential triphosphate, d. TTP, ready for monophosphate for DNA synthesis (d. TMP) to proceed. DNA synthesis.

Cycle des cofacteurs r. ADP This completes the cofactor cycling r. CDPTheribonucleotide section. cofactor, methylene tetrahydrofolate, donates a methyl r. GDP reductase group to d. UMP. The resulting r. UDP dihydrofolate is recycled. The recycling starts with the reaction allosteric catalyzed by dihydrofolate reductase. feedback DNA d. NTP d. ADP, d. CDP, d. GDP, d. UDP Étape suivante Sujet suivant methylene tetrahydrofolate Recommencer Sujet précédent Faire un essai d. UMP Tutoriale thymidylate synthase d. TDP Structure & Function des protéines chez les animaux tetrahydrofolate d. TMP dihydrofolate reductase Aide Son : oui/non Contenu Index Quitter Thethymidine most important enzyme for Thymidylate synthase activity The triphosphate (TTP) regulation ofimportant production of isnormal essential for DNA synthesis. pathway provides an deoxynucleoside tri-phosphates in example of the regulation of enzyme the body reductase. activity in istheribonucleotide body. Enzymes are represented as green rectangles. Thymidylate synthase enzyme adds a for Thymidylate The most important synthase activity methyl group d. UMP. The methyl is normal essential regulation forto. DNA of synthesis. production of group comes from the cofactor, deoxynucleoside tri-phosphates in methylene the body tetrahydrofolate, is ribonucleotide reductase. which is converted to dihydrofolate. Thymidylate adds a back Thymidylatesynthase activity Dihydrofolate is recycled methyl groupfor to d. UMP. The methyl essential DNA synthesis. toismethylene tetrahydrofolate. group comes from the cofactor, Dihydrofolate reductase catalyzes methylene tetrahydrofolate, the first step in recycling. which is converted to dihydrofolate.

Deux médicaments anti-cancer r. ADP DNA synthesis is essential for cell ribonucleotide r. CDP proliferation. Thus, fluorouracil and r. GDP reductase methotrexate, in preventing DNA r. UDP inhibit cell proliferation. synthesis, d. ADP, d. CDP, d. GDP, d. UDP Étape suivante This prevents tumors from growing, butallosteric also interferes with those normal cells that need to proliferate, feedback producing side-effects. DNA d. NTP Sujet suivant methylene tetrahydrofolate d. UMP thymidylate synthase Recommencer Sujet précédent Faire un essai fluorodeoxyuridylate methotrexate d. TDP Structure & Function des protéines chez les animaux d. TMP dihydrofolate Tutoriale tetrahydrofolate dihydrofolate reductase Aide Son : oui/non Contenu Index Quitter Fluorodeoxyuridylate Thymidylate synthase is and a dihydrofolate suicide inhibitor reductase of thymidylate are the most important synthase. Fluorodeoxyuridylate targets forformed is anti-cancer in thetherapy, cell from the in thisfluorouracil. drug, pathway. Fluorodeoxyuridylate Methotrexate is a competitive is a suicide inhibitor of dihydrofolate of thymidylate synthase. reductase. Fluorodeoxyuridylate (DHFR). is formed in the cell from the drug, uracil. Either Methotrexate fluorouracil is a competitive or methotrexate inhibitor of dihydrofolate has the effect of blocking reductasethe (DHFR). conversion of d. UMP to d. TMP, thus preventing DNA synthesis.

Sommaire r. ADP r. CDP ribonucleotide r. GDP reductase r. UDP d. ADP, d. CDP, d. GDP, d. UDP Étape suivante allosteric feedback DNA Structure & Function des protéines chez les animaux Sujet suivant methylene tetrahydrofolate d. NTP d. UMP thymidylate synthase Sujet précédent Faire un essai fluorodeoxyuridylate methotrexate d. TDP Recommencer d. TMP dihydrofolate Tutoriale tetrahydrofolate dihydrofolate reductase Aide Son : oui/non Contenu Index Quitter Which enzyme regulates the rate of production of deoxyribonucleoside 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. )

Aide • 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. Structure & Function des protéines chez les animaux Étape suivante Sujet suivant Recommencer Sujet précédent Faire un essai Tutoriale Aide Son : oui/non Contenu Index Quitter