Simon Ebbinghaus and Harshita Rastogi (left) have studied the function of enzymes under various conditions.
Chemistry
Robust Enzymes
The molecules surrounding them have a major influence on how enzymes function. Not only the size of neighboring molecules, but also their chemical properties are crucial.
Cells must produce energy despite changing conditions. But what keeps metabolic enzymes functional during temperature fluctuations? A team led by Prof. Simon Ebbinghaus and Dr. Harshita Rastogi at Ruhr University Bochum and the Research Center Chemical Sciences and Sustainability investigated this question using phosphofructokinase-1 platelet isoform (PFKP), a central enzyme in glucose metabolism. They found that thermal protection depends less on the size of crowding molecules than on the subtle chemical interactions among them, which can determine how well the enzyme remains active as temperatures rise. Their work was published in the science magazine Angewandte Chemie International Edition from October 8, 2026.
A crowded world inside cells
Enzymes are molecular machines that drive the biochemical reactions of life. PFKP controls a key step in glycolysis, the pathway through which cells convert glucose into energy and molecular building blocks. Enzymes do not function in isolation: inside cells, they are surrounded by proteins, sugars, and many other molecules. “This molecular environment changes when cells experience stress, reorganize their metabolism, or form temporary enzyme assemblies”, explains Simon Ebbinghaus. “A key question has therefore remained open: is it mainly the limited space around an enzyme that matters, or is the chemical nature of its neighbors equally important?”
More than a matter of size, chemical surroundings tune enzyme function
To investigate this, the researchers studied PFKP in controlled solutions containing crowding molecules of different sizes and chemical properties. They measured how enzyme activity changed with temperature, assessed its structural stability, and used molecular simulations to examine interactions that cannot be observed directly in experiments.
All crowded environments reduced PFKP activity at lower temperatures. “At higher temperatures, however, the results revealed a striking difference”, says Harshita Rastogi: “Sugar-based molecules, including glucose and dextran (a glucose polymer) helped PFKP retain activity over a broader temperature range.” Because glucose and the much larger dextran had similar effects, molecular size alone could not explain the result. Instead, the findings point to the importance of “soft” chemical interactions: weak, reversible contacts among the surrounding molecules, the enzyme, and its substrates. The simulations showed that these molecules can influence regions near the enzyme’s active site, affecting both enzyme flexibility and substrate positioning.
A clue to metabolism under stress
An enzyme must be flexible enough to catalyze its reaction while holding its substrates in the correct position. Sugar-based environments appear to tune this balance, making PFKP more robust at elevated temperatures. The enzyme is not simply protected from unfolding; its dynamics and catalytic behavior are shaped by its local environment.
The study suggests that cellular crowding is not merely a physical traffic jam: “The chemical composition of the surrounding molecules may actively influence how metabolic enzymes respond to stress”, says Simon Ebbinghaus. Future research will need to determine whether cells exploit such local chemical environments to preserve metabolic activity under challenging conditions.
