KSI has been used as a model system to test different theories to explain how enzymes achieve their catalytic efficiency. Low-barrier hydrogen bonds and unusual pKa values for the catalytic residues have been proposed as the basis for the fast action of KSI.   Gerlt and Gassman proposed the formation of unusually short, strong hydrogen bonds between KSI oxanion hole and the reaction intermediate as a means of catalytic rate enhancement.   In their model, high-energy states along the reaction coordinate are specifically stabilized by the formation of these bonds. Since then, the catalytic role of short, strong hydrogen bonds has been debated.   Another proposal explaining enzyme catalysis tested through KSI is the geometrical complementarity of the active site to the transition state, which proposes the active site electrostatics is complementary to the substrate transition state . 
The fetal adrenal cortex lacks expression of the enzyme early on, thus mineralocorticoids (. aldosterone ) and glucocorticoids (. cortisol ) cannot be synthesized. This is significant because cortisol induces type II pneumocytes of the lungs to synthesize and secrete pulmonary surfactant ; without pulmonary surfactant to reduce the alveolar surface tension , premature neonates may die of neonatal respiratory distress syndrome . If delivery is unavoidable (. because of placental abruption , or pre-eclampsia / HELLP syndrome ), then glucocorticoids (. cortisol) can be administered.