The Effect of Cations on the Amidase Activity of Human Tissue Kallikrein: 1-Linear Competitive Inhibition by Sodium, Potassium, Calcium and Magnesium. 2-Linear Mixed Inhibition by Aluminium

Abstract

Hydrolysis of D-valyl-L-leucyl-L-arginine p-nitroanilide by human tissue kallikrein (hK1) was studied in the absence and in the presence of increasing concentrations of the following chloride salts: sodium, potassium, calcium, magnesium and aluminium. The data indicate that the inhibition of hK1 by sodium, potassium, calcium and magnesium is linear competitive and that divalent cations are more potent inhibitors of hK1 than univalent cations. However the inhibition of hK1 by aluminium cation is linear mixed, with the cation being able to bind to both the free enzyme and the ES complex. This cation was the best hK1 inhibitor. Aluminium is not a physiological cation, but is a known neurotoxicant for animals and humans. The neurotoxic actions of aluminium may relate to neuro-degenerative diseases.

Key Words:

• Human tissue kallikrein cation inhibition
• Tissue kallikrein inhibition
• Enzyme inhibition
• Enzyme kinetics
• Human kallikrein