PPT Capstone...20 Dec 10

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Presentation For Capstone Project

ForThe partial fulfillment of B.Tech

(Biotech.) Hons.

Dec20, 2010

Topic: Metabolic role of humanp53 in cancer

By:

Rahul ThakurRoll Number A77E401

Section A77E4

Guide : Dr. Abhay Kumar


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Objective.

The objective of the current work was to collectthe information from the related and recent

articles and present some logical conclusionsout of it.

-and to focus mainly on the role of p53 in cancermetabolism


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Role of

p53


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Recent researches suggests that p53, the

most commonly mutated tumor suppressor

gene, might play an important role in theregulation of energy generating metabolic

pathways, that switch from oxidative

phosphorylation to glycolysis

p53


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generation of ATP through oxidative phosphorylation isan efficient and preferred metabolic process,

which produces far more ATP molecules from a given

amount of glucose compared with glycolysis.However, when the ability of cells to generate ATPthrough mitochondrial oxidative phosphorylation iscompromised, cells are able to adapt alternativemetabolic pathways, such as increasing glycolyticactivity, to maintain their energy supply.


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As per Warburg when the

cell is present in thenormal state i.e., in normalOxygen level it follows the

Krebs's cycle pathway, but

under the stress conditionswhen the oxygen levelbecomes low the cancercells automatically shifttheir metabolism to the

glycolysis

http://TheNaturalCancerCure.com

Review Of Literature


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Objections

Since according to the Warburg cancercell follow the glycolysis when O2 level islow ..but many researchers found thateven in the adequate amount of the O2cancer cell still follow glycolysis


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possible Target ???


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pyruvate kinase has emerged as a keyplayer in maintaining the altered

metabolism of cancer cells and is thus apotential target for cancer drugs.


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Glycolysis Pathway

Target

Protein Kinase-M2


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Protein Kinase exists in two

formsdimeric form and tetrameric form

which shows a high affinity for the substrate

phosphoenolpyruvate (PEP), and the dimeric form,which has a low affinity for PEP. The dimeric form

predominates in tumours and was thereforenamed Tumor M2-PK


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Tumour cells have been shown to

express exclusively the embryonic M2isoform of pyruvate kinase.


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Either Supress this glycolysis pathway

Block the target enzymeseg.fructose

1-6 biphosphate Make the PMK1 active


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Conclusion

After this elaborate study we can conclude

that there are certain pathways involved incancer which can be regulated at specificstages before onset of cancer that can betargeted to design drugs which can beeffective against preventing cancer


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ReferencesVausden .et al.( 2006 ) p53: new roles in metabolism TRENDS in Cell Biology

Vol.17 No.6

Sabatini Hsu .et al. (2004) Cancer Cell Metabolism:Warburg and Beyond cell biology

Heather R. Christofk1, Matthew G. Vander Heiden1,3, Ning Wu1, John M. Asara2,4

& Lewis C. Cantley1,4

Christofk, H. R.; Vander Heiden, M. G.; Harris, M. H.;Ramanathan, A.; Gerszten, R. E.; Wei, R.; Fleming, M. D.; Schreiber, S. L.; Cantley,L. C.: The M2 splice isoform of pyruvate kinase is important for cancer metabolismand tumour growth. Nature 452: 230-233, 2008.

9. Matoba,

Matoba, S. et al. (2006) p53 regulates mitochondrial respiration.Science 312, 16501653


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Thank you

PPT Capstone...20 Dec 10

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