Warburg effect complete information.

1. WARBURG EFFECT (AEROBIC GYLCOLYSIS)
1931 NOBLE PRIZE
WINNER

2. Overview
• Introduction
• Causes of Warburg Effect
• Significance of Warburg Effect
• References

3. Introduction
• Warburg, considered by many the pre-eminent bio
chemist of the first half of the twentieth century, made
vital contributions to many other areas of biochemistry,
including respiration, photosynthesis, and the
enzymology of intermediary metabolism.

4. • In the mid 1920s Otto Warburg and co-workers
showed that, under Aerobic conditions, tumour tissues
metabolize approximately tenfold more glucose to
lactate in a given time than normal tissues.

5. • Question
WHY its advantageous for a cancer cell to rely on
seemingly inefficient glycolysis (which generate 2
molecules of ATP per molecule of glucose ) instead of
oxidative phosphorylation (which generates up to 36
molecules of ATP per molecules of glucose)

6. • ANSWER
• Aerobic glycolysis provides rapidly dividing tumour
cells with metabolic intermediates that are needed
for the synthesis of cellular components , where as
mitochondrial oxidative phosphorylation does not

7. • Its important to recognize that rapidly growing normal
cells such as , in embryonic tissues also relay on
aerobic fermentation.
• Thus “Warburg metabolism “ is not cancer specific ,
but instead is a general property of growing cells that
become fixed in cancer cells

8. • This phenomenon later came to be known as
“Warburg Effect”. • Warburg purified and crystallized
seven of the enzymes of glycolysis.
• He used a tool called as “ Warburg Manometer”
which measured directly the consumption of oxygen
by monitoring changes in gas volume, and therefore
allowed quantitative measurement of any enzyme
with oxidase activity.

9. Some Features of Warburg Effect
• Glucose uptake and glycolysis proceed about ten
times faster in most solid tumours than in non-
cancerous tissues.
• Tumour cells commonly experience hypoxia (limited
oxygen supply), because they initially lack an
extensive capillary network to supply the tumour with
oxygen.

10. • The high glycolytic rate may also result in part from
smaller numbers of mitochondria in tumour cells thus
resulting in less ATP generation and higher
consumption of Energy (ATP).

11. • In some cases, tumour cells overproduce several
glycolytic enzymes, including an isozyme of
Hexokinase-II and it results in committing the cell to
continued glycolysis.
• HIF-1 is a protein that stimulates the activity of eight
glycolytic enzymes and it gives tumour cell capacity to
survive Anaerobic conditions.

12. Causes of Warburg Effect
• Mitochondrial Defects: mtDNA mutations lead to malfunction in
respiration and oxidative phosphorylation.
• Hypoxia : Possible adaptation owing to lack of Oxygen availability in
the Environment.
• Oncogenic Signals : Point Mutations in genes such as Ras family can
result in proliferation of cells and signal initiation.
• Altered Metabolic Enzymes: Overproduction and mimicking of
metabolic enzymes such as Hexokinase-II result in increased Glycolytic
activity

13. Significance of Warburg Effect
• Scientists after extensive research came to the
conclusion that most Tumour cells exhibit high
glycolytic uptake.
• Taking cue from this mechanism, numerous Glycolytic
Inhibitors have been developed. These compounds
are acting as potential anti- cancer agents.

14. • Alpha-cyano-4-hydroxycinnamic acid is a glycolytic
inhibitor that has been successfully used in Brain
Cancer.
• Recently, a molecule named Di ChloroAcetic or DCA
acid was devised by University of Alberta, claiming
that it’s introduction would result in normal
functioning of Mitochondria. The testing of this
compound’s claims are underway.

15. Why PET/CT Works: The Warburg Effect
● Normal Cells
• Low rate of glycolysis
• Aerobic metabolism
● Most Cancer Cells
• High rate of glycolysis
• Anaerobic metabolism

16. • Glucose hunger of tumour is used to visualize tumours
via PET scanning , in which patients are injected with
18F-Fluorodeoxyglucose , a nonmetabolizable
derivative of glucose that sis preferentially taken up
into tumour cells ( as well as normal , actively dividing
tissues such as bone marrow )

17. References
• ROBBINS 10 edition.
• target

18. THANK YOU