discoveries magazine

Beware of Watchdog Enzyme

Illustration: Neil Webb

A common enzyme reveals itself as an alarm for the immune system.

A study by Cedars-Sinai investigators is providing clues to some of the mysteries surrounding the human immune system, which is the body’s defense against harmful microbes.

The team has discovered that an enzyme associated with energy production also plays a key role in boosting immunity to disease. The study reveals that the enzyme hexokinase functions as an alert system for the body: It stands guard against bacteria, alerts the immune system when it identifies an attack, and then initiates a defense. The enzyme accomplishes all of this by binding to sugar in the cell walls of harmful bacteria, thus activating proteins to trigger an inflammatory response against the assailants. The finding helps explain how the immune system “knows” certain bacteria are harmful.

Hexokinase is not specific to the immune system — it’s also a common enzyme that’s necessary for cells to utilize glucose as a source of energy. “The dual role of this enzyme in metabolism and innate immunity is surprising,” says David Underhill, PhD, the Janis and William Wetsman Family Chair in Inflammatory Bowel Disease, research scientist in the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute at Cedars-Sinai, and the study’s principal investigator.

The discovery of hexokinase’s two functions has far-reaching implications. It may help explain why chronic, low-level inflammation is often found in patients with obesity, Type 2 diabetes, and coronary artery disease. These serious conditions, which affect millions of Americans, are intertwined with metabolism, the chemical process by which the body uses food and other substances to make energy, grow, and heal.