Warburg Effect : Introduction, Causes, Consequences

1. Warburg Effect
Presented By: D.Sairam
Course : Fundamentals of Biology- Life
Sciences
Course Code: BSBT-201
Course Instructor: Dr. Subhabrata Kar
Presentation Code: U3P1

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.
• In the mid 1920s 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.
• 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.

4. Note: Warburg Effect in Plant Physiology and Oncology are different
• In Plant physiology, Warburg Effect refers to the phenomenon in which Oxygen acts as a competitive inhibitor
to Carbon dioxide fixation under the influence of RuBisCO, which initiates photosynthesis.
Source
: Bild-1928

5. Comparison of Glycolysis between a Normal Tissue and Tumour/ Proliferated Tissue
• http://pharmaceuticalintelligence.com/2012/10/17/is-the-
warburg-effect-the-cause-or-the-effect-of-cancer-a-21st-
century-view/

6. 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.
 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).
 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.

7. 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.

8. 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.
 Alpha-cyano-4-hydroxycinnamic acid is a glycolytic inhibitor that has been
successfully used in Brain Cancer.
 Recently, a molecule named Di Chloro Acetic 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.

9. References
• http://www.nature.com/onc/journal/v25/n34/fig_tab/1209597t2.html#figure-
title
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849637/
• http://medical-dictionary.thefreedictionary.com/Warburg+effect
• http://www.esscientificconsulting.com/
• https://www.youtube.com/results?search_query=warburg+effect+
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849638
• http://pharmaceuticalintelligence.com/2012/10/17/is-the-warburg-effect-the-
cause-or-the-effect-of-cancer-a-21st-century-view/
• http://abbs.oxfordjournals.org/content/45/1/18.full
• http://dx.doi.org/10.4161%2Fcc.9.12.11989
• http://www.jefferson.edu/cancerbiology/faculty_profile.cfm?key=mpl001

10. Thank You