Régulation de la production d’un nucléotide triphosphate
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Transcript of Régulation de la production d’un nucléotide triphosphate
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
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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
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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.
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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.
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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.
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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.)
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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
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