PGK1, a glycolytic enzyme, promotes brain tumor formation and cancer metabolism

PGK1, a glycolytic enzyme, promotes brain tumor formation and cancer metabolism

Normal cells generate oxygen for survival via a relatively low rate of glycolysis, which converts glucose into the enzyme pyruvate. Pyruvate is used in the citric acid cycle (TCA), a series of chemical reactions that generate energy.

Cancer cells however produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cell, a process that converts glucose into cellular energy and forms lactic acid. Normal healthy cells will bypass this fermentation process if oxygen is available.

Malignant, rapidly growing tumors can experience glycolytic rates up to 200 times higher than those of healthy cells and will undergo lactic acid fermentation even in the presence of high oxygen levels.

PGK1, a glycolytic enzyme, has been found to play a role in coordinating cellular processes crucial to cancer metabolism and brain tumor formation, according to results published in today's online issue of Molecular Cell.

The paper sheds further light on the Warburg effect, an enzymatic pathway that cancer cells employ to boost energy levels and produce cellular substances that lead to rapid cancer growth.

"The Warburg effect is characterized by increased levels of glucose, lactate production and suppression of pyruvate metabolism in mitochondria," said the author. "Exactly how this process is coordinated with cancer metabolism has been little understood."

The team found that a cellular chain of events involving activation of cancer genes like EGFR, KRAS and B-Raf and the protein ERK, allowed PGK1 to "translocate" into the cell's mitochondria. Mitochondria are membrane-containing cell components crucial for producing energy.

PGK1 acted as a protein kinase in mitochondria and activated a critical enzyme that inhibited the mitochondria's ability to use pyruvate, suppressed chemically reactive molecules containing oxygen and increased lactate levels.