Régulation de la production Régulation de la production d’un nucléotide triphosphated’un nucléotide triphosphate

Uridylate en thymidylate

Cycle des Cofacteurs

Deux médicaments anti-cancer

Structure & Function des protéines chez les animaux

Régulation allostérique

Sommaire

The thymidine triphosphate (TTP) pathway provides an important example of the regulation of enzyme activity in the body.

Enzymes are represented as green rectangles.

ribonucleotidereductase

Ribonucleotide reductase controls the production of deoxynucleoside tri-phosphates in the body.

DNA

Enzymes are represented as green rectangles.

Ribonucleotide reductase controls the production of deoxynucleoside tri-phosphates 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.

dNTP

DNA is synthesized from deoxyribonucleoside triphosphates (dNTPs) by an enzyme, DNA polymerase, which is represented by the unlabeled green rectangle.

rADPrCDPrGDPrUDP

The purpose of this pathway is the synthesis of DNA.

DNA is synthesized from deoxyribonucleoside triphosphates (dNTPs) by an enzyme, DNA polymerase, which is represented by the unlabeled green rectangle.

Here are the four differentribonucleoside diphosphates

dADP, dCDP, dGDP, dUDP

which are converted, byribonucleotide reductase, todeoxyribonucleosidediphosphates.

DNA is synthesized from deoxyribonucleoside triphosphates (dNTPs) by an enzyme, DNA polymerase, which is represented by the unlabeled green rectangle.

Here are the four differentribonucleoside diphosphateswhich are converted, byribonucleotide reductase, todeoxyribonucleosidediphosphates.

Three of the deoxyribo-nucleoside diphosphates areconverted to deoxyribo-nucleoside triphosphates byphosphorylation reactions.

dNTP

Inhibitionallostérique

Regulation allostériqueRegulation allostérique Structure & Function des protéines chez les animaux

Sujet suivant

Sujet précédent

Étape suivante

Recommencer

Faire un essai

Aide

Son :oui/non

Quitter

Contenu

Here are the four differentribonucleoside diphosphateswhich are converted, byribonucleotide reductase, todeoxyribonucleosidediphosphates.

Three of the deoxyribo-nucleoside diphosphates areconverted to deoxyribo-nucleoside triphosphates byphosphorylation reactions.

This 2-enzyme pathway isregulated by negative feedback.When the dNTP concentrationrises, some of the dNTP bind toto ribonucleotide reductasemolecules and decrease theiractivity by allosteric inhibition.

This completes the allosteric regulationsection. Note that ribonucleotidereductase catalyzes the committed stepthat inexorably leads to the dNTPs andDNA synthesis. Hence, ribonucleotidereductase is allosterically regulated tocontrol the flow through the pathwayand hence the rate of production of thedNTPs. Click again to move on to thenext step, uridylate to thymidylate.

Index

Tutoriale

The thymidine triphosphate (TTP) pathway provides an important example of the regulation of enzyme activity in the body.

Enzymes are represented as green rectangles.

ribonucleotidereductase

Ribonucleotide reductase controls the production of deoxynucleoside tri-phosphates in the body.

DNA

Enzymes are represented as green rectangles.

Ribonucleotide reductase controls the production of deoxynucleoside tri-phosphates 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.

dNTP

DNA is synthesized from deoxyribonucleoside triphosphates (dNTPs) by an enzyme, DNA polymerase, which is represented by the unlabeled green rectangle.

rADPrCDPrGDPrUDP

The purpose of this pathway is the synthesis of DNA.

DNA is synthesized from deoxyribonucleoside triphosphates (dNTPs) by an enzyme, DNA polymerase, which is represented by the unlabeled green rectangle.

Here are the four differentribonucleoside diphosphates

dADP, dCDP, dGDP, dUDP

which are converted, byribonucleotide reductase, todeoxyribonucleosidediphosphates.

DNA is synthesized from deoxyribonucleoside triphosphates (dNTPs) by an enzyme, DNA polymerase, which is represented by the unlabeled green rectangle.

Here are the four differentribonucleoside diphosphateswhich are converted, byribonucleotide reductase, todeoxyribonucleosidediphosphates.

Three of the deoxyribo-nucleoside diphosphates areconverted to deoxyribo-nucleoside triphosphates byphosphorylation reactions.

dNTP

Inhibitionallostérique

Regulation allostériqueRegulation allostérique Structure & Function des protéines chez les animaux

Sujet suivant

Sujet précédent

Étape suivante

Recommencer

Faire un essai

Aide

Son :oui/non

Quitter

Contenu

Here are the four differentribonucleoside diphosphateswhich are converted, byribonucleotide reductase, todeoxyribonucleosidediphosphates.

Three of the deoxyribo-nucleoside diphosphates areconverted to deoxyribo-nucleoside triphosphates byphosphorylation reactions.

This 2-enzyme pathway isregulated by negative feedback.When the dNTP concentrationrises, some of the dNTP bind toto ribonucleotide reductasemolecules and decrease theiractivity by allosteric inhibition.

This completes the allosteric regulationsection. Note that ribonucleotidereductase catalyzes the committed stepthat inexorably leads to the dNTPs andDNA synthesis. Hence, ribonucleotidereductase is allosterically regulated tocontrol the the rate of pr flow through the pathwaéand hence oduction of thedNTPs. Click again to move on to thenext step, uridylate to thymidylate.

Index

Tutoriale

ribonucleotidereductase

rADPrCDPrGDPrUDP

dADP, dCDP, dGDP, dUDP

dNTPDNA dNTP

allostericfeedback

Here is the negative feedbackloop regulating the productionof deoxyribonucleoside tri-phosphates.

Uridylate requires the additionof a methyl group, to makethymidylate, for DNAsynthesis. The first step isdephosphorylation todeoxyuridine monophosphate.

dUMP

dTMP

thymidylatesynthase

The methyl group is added bythymidylate synthase, whichconverts dUMP to thymidinemonophosphate (dTMP)

dTDP

Uridylate en Uridylate en thymidylatethymidylate

Structure & Function des protéines chez les animaux

Uridylate requires the additionof a methyl group, to makethymidylate, for DNAsynthesis. The first step isdephosphorylation todeoxyuridine monophosphate.

The methyl group is added bythymidylate synthase, whichconverts dUMP to thymidinemonophosphate (dTMP).

Two phosphorylation events convert dTMP to thymidinetriphosphate, dTTP, ready forDNA synthesis.

The methyl group is added bythymidylate synthase, whichconverts dUMP to thymidinemonophosphate (dTMP).

Two phosphorylation events convert dTMP to thymidinetriphosphate, dTTP, ready forDNA synthesis.

DNA synthesis requires all fourdeoxyribonucleoside tri-phosphates, so dTTP is essentialfor DNA synthesis to proceed.

This completes the uridylate tothymidylate section. Note thatthymidylate synthase is essentialto make dTTP and hence DNA.Click again to move on to the nextsection, cofactor cycling.

Sujet suivant

Sujet précédent

Étape suivante

Hit P to go back

Faire un essai

Aide

Son :oui/non

Quitter

Contenu

Index

Tutoriale

Recommencer

rADPrCDPrGDPrUDP

ribonucleotidereductase dADP, dCDP, dGDP, dUDP

dNTPDNA dNTP

allostericfeedback

dUMP

thymidylatesynthase

thymidylatesynthase

dTMPdTDP

The thymidine triphosphate (TTP)pathway provides an importantexample of the regulation of enzymeactivity in the body. Enzymes arerepresented as green rectangles.

The most important enzyme fornormal regulation of production ofdeoxynucleoside tri-phosphates inthe body is ribonucleotide reductase.

Thymidylate synthase activityis essential for DNA synthesis.

thymidylatesynthase

The most important enzyme fornormal regulation of production ofdeoxynucleoside tri-phosphates inthe body is ribonucleotide reductase.

methylenetetrahydrofolate

Thymidylate synthase activityis essential for DNA synthesis.

Thymidylate synthase adds amethyl group to dUMP. The methylgroup comes from the cofactor,methylene tetrahydrofolate,

dihydrofolate

which is converted to dihydrofolate.

tetra-hydrofolate

Thymidylate synthase activityis essential for DNA synthesis.

Thymidylate synthase adds amethyl group to dUMP. The methylgroup comes from the cofactor,methylene tetrahydrofolate,which is converted to dihydrofolate.

Dihydrofolate is recycled backto methylene tetrahydrofolate.

dihydrofolatereductase

Cycle des Cycle des cofacteurscofacteurs

Structure & Function des protéines chez les animaux

Dihydrofolate reductase catalyzesthe first step in recycling.

This completes the cofactor cyclingsection. The cofactor, methylenetetrahydrofolate, donates a methylgroup to dUMP. The resultingdihydrofolate is recycled. Therecycling starts with the reactioncatalyzed by dihydrofolatereductase.

Sujet suivant

Sujet précédent

Étape suivante

Faire un essai

Aide

Son :oui/non

Quitter

Contenu

Index

Tutoriale

Recommencer

Deux médicaments anti-Deux médicaments anti-cancercancer

Structure & Function des protéines chez les animaux

rADPrCDPrGDPrUDP

ribonucleotidereductase dADP, dCDP, dGDP, dUDP

dNTPDNA dNTP

allostericfeedback

dUMP

thymidylatesynthase

thymidylatesynthase

dTMPdTDP

thymidylatesynthase

methylenetetrahydrofolate

dihydrofolate

tetra-hydrofolate

dihydrofolatereductase

Thymidylate synthase anddihydrofolate reductase arethe most important targetsfor anti-cancer therapy,in this pathway.

fluorodeoxy-uridylate

Fluorodeoxyuridylate is asuicide inhibitor of thymidylatesynthase. Fluorodeoxyuridylateis formed in the cell from thedrug, uracil.

methotrexate

Methotrexate is a competitive inhibitor of dihydrofolatereductase (DHFR).

Fluorodeoxyuridylate is asuicide inhibitor of thymidylatesynthase. Fluorodeoxyuridylateis formed in the cell from thedrug, fluorouracil.

Methotrexate is a competitive inhibitor of dihydrofolatereductase (DHFR).

Either fluorouracil ormethotrexate has the effect ofblocking the conversion ofdUMP to dTMP, thuspreventing DNA synthesis.

DNA synthesis is essential for cellproliferation. Thus, fluorouracil andmethotrexate, in preventing DNAsynthesis, inhibit cell proliferation.This prevents tumors from growing,but also interferes with those normalcells that need to proliferate,producing side-effects.

Sujet suivant

Sujet précédent

Étape suivante

Faire un essai

Aide

Son :oui/non

Quitter

Contenu

Index

Tutoriale

Recommencer

SommairSommairee

Structure & Function des protéines chez les animaux

rADPrCDPrGDPrUDP

ribonucleotidereductase dADP, dCDP, dGDP, dUDP

dNTPDNA dNTP

allostericfeedback

dUMP

thymidylatesynthase

thymidylatesynthase

dTMPdTDP

thymidylatesynthase

methylenetetrahydrofolate

dihydrofolate

tetra-hydrofolate

dihydrofolatereductase

fluorodeoxy-uridylate

methotrexate

Which enzyme regulates therate of production of deoxy-ribonucleoside triphosphates?

How does thymidine phosphatediffer from uridine phosphate?

This is the end of this module.

(Hint: click on the questions atthe left to hear the answer.Click the “Take a test” button, above, for more questions.)

Sujet suivant

Sujet précédent

Étape suivante

Faire un essai

Aide

Son :oui/non

Quitter

Contenu

Index

Tutoriale

Recommencer

AidAidee• 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.

• 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

Sujet suivant

Sujet précédent

Étape suivante

Faire un essai

Aide

Son :oui/non

Quitter

Contenu

Index

Tutoriale

Recommencer