The document summarizes Otto Warburg's discovery of the Warburg effect. Warburg showed in the 1920s that tumor cells metabolize glucose to lactate at a much higher rate than normal cells, even in the presence of oxygen. This is known as aerobic glycolysis or the Warburg effect. The document then discusses various causes and mechanisms of the Warburg effect, including mutations, hypoxia in tumor microenvironments, overexpression of glycolytic enzymes, and mitochondrial dysfunction in cancer cells. It also notes some characteristics of the Warburg effect such as cancer cell adaptations to hypoxia and maintenance of an intracellular alkaline pH.

1. WARBURG’S
EFFECT
PRESENTED BY:
Vivek kumar
M.Sc Microbiology
Bangalore University

2. INTRODUCTION
• The German biochemist Otto Warburg was the first to show; as
early as 1928, that tumors have a higher rate of glucose
metabolism than other tissues.
• 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.
•
•Warburg effect, high glycolytic metabolism even under normoxic
conditions, is an adaptation of cancer cells to rapid fluctuations
in energy demand.

3. •Warburg purified and crystallized seven of the enzymes of
glycolysis. In these studies he developed and used an
experimental tool that revolutionized biochemical studies of
oxidative metabolism: the Warburg manometer , which measured
directly the consumption of oxygen by monitoring changes in gas
volume.

4. COMPARISON OF GLYCOLYSIS BETWEEN A NORMAL TISSUE AND
TUMOUR/ PROLIFERATED TISSUE
Adapted from A. Fadaka etal./Journal of Oncological Sciences 3(2017)

5. CAUSES OF WARBURG’S EFFECT
• Warburg’s Effect is a metabolic adaptations in cancer cells.
Tumor microenvironment effects the tumor metabolism
• Mutations cause in a cell activates the oncogenes and
deactivates the Tumor Suppressor Genes which causes anormal
development.
• Tumor cells commonly experience hypoxia(limited oxygen
supply) because they initially lack an extensive capillary network
to supply the tumor with oxygen.

6. • Fast growing cancer cells will require more energy for their
survival and proliferation, therefore cancer cell use a primitive
inefficient reaction , aerobic glycolysis, to generate
considerate amount of energy.
• Mitochondrial Dysfunction plays a causative role in
Warburg’s Effect. Cancer cells have lesser no. of
mitochondria, therefore they rely upon inefficient glycolytic
mode of ATP synthesis rather than respiration.

7. MECHANISMS OF WARBURG’S EFFECT
• Glycolytic Enzymes such as Glut1 & Glut3 , pyruvate kinase,
Lactate Dehydrogenase , Phosphofructokinase, hexokinase is
overexpressed.
•Pyruvate transport into the mitochondrial matrix through its
specific carrier is decreased due to overexpression of Lactate
dehydrogenase .
• Mutations in succinate dehydrogenase (SDH) impair its activity.
Mitochondria ATP synthase activity is restricted by the
overexpression of its inhibitory subunits.

8. Adapted from A. Fadaka etal./Journal of Oncological Sciences 3(2017)
Fig showing: Glycolysis in tumor cells

9. CHARACTERISTICS OF WARBURG’S EFFECT
• Cancer Cell adaptations to hypoxia conditions :
The transcription factor hypoxia-inducible factor-1 (HIF-1) is a key
regulator responsible for the induction of genes that facilitate
adaptations.
• Mitochondrial Dysfunction :
.Mitochondria are key components of the apoptotic cell death process.
Due to overexpression of Hexokinase II prevent interaction of
proapoptotic proteins with mitochondria
Alkalosis :
Tumors shows a reversed pH gradient with a constitutively
increased intracellular pH that is higher than extracellular pH.

10. REFERENCE
• A.Fadaka etal./ Journal of Oncological Sciences 3 (2017),
Biology of Glucose metabolization in cancer cells
• Michelle Potter , Emma Newport and Karl J. Morten ,The
Warburg Effect
• Slobodan Devic, Warburg effect- a consequence or the
cause of Carcinogenesis.(2016)
• Lehninger Principles of Biochemistry, Fourth Edition

11. THANK YOU