Description
Plasma kallikrein possesses a unique protein structure
with four apple domains and a trypsin domain, which evolved
before coagulation factor XI. Tissue kallikreins are trypsinbased enzymes, and some members are highly correlated with
prostate cancer. The evidence that human urine induces hypotension
when injected intravenously into anesthetized dogs was
first described in 1909. Two major kallikreins, plasma kallikrein (KLKB1) and tissue (glandular) kallikrein (KLK),
were found in mammals, and they were transcribed by
different genes. Glandular KLK was an old name and
was replaced by tissue KLK in the modern nomenclature.
Chemical Properties
Kallikrein, a substance extracted from the porcine submandibular gland or pancreas, has vasodilatory properties. It is a white or off-white powder; it is readily soluble in water (10%) and dilute alcohol, but insoluble in concentrated ethanol and common organic solvents. It forms a colorless or slightly yellowish clear solution when dissolved in water or saline. It is relatively stable at pH 4.5 to 7.8. It is unstable to heat, strong acids, strong bases, and oxidants. Its isoelectric point ranges from 3.9 to 4.37. Generally speaking, higher purity indicates lower stability. The dry powder maintains its activity for several months at -20°C. It can be stored frozen in water and buffer at a pH of 8 for considerable periods without inactivation. Heavy metal ions such as Hg2+, Ca2+, Mn2+, and Ni2+ inhibit it to varying degrees (Ca2+ and Mg2+ have no effect on enzyme activity). Thiol compounds and chelating agents such as EDTA can reverse the inhibition caused by metal ions. Conversely, high concentrations of Ca2+ (1 mol L^-1) can increase enzyme activity by 15% to 20%. Certain trypsin inhibitors, such as aprotinin and diisopropyl phosphate, inhibit both pancreatic and submandibular gland kallikrein.
Uses
Kallikrein from porcine pancreas has been used:
- as a matrix metalloproteinase-9 (MMP-9) zymogen activator
- as a component of cell culture to test its effect on rat subventricular zone (SVZ) cells and oligodendrocyte progenitor cells (OPC) proliferation and survival
- as a model enzyme to track kinetic data and visual detection limits of hydrolysis by hydrolytic enzymes in the two-phases array
General Description
Kallikrein exists as an inactive prokallikrein in the porcine pancreas. The porcine kallikrein gene region is localized on chromosome 6q12-q21.
Biochem/physiol Actions
Kallikrein active forms are generated by the enzymatic action of trypsin. It is a serine protease that mediates the activation of growth factors and substrates.
Clinical Use
Kallikreins are drug targets for the control of hypertension, inflammation, and blood coagulation diseases. They
are also possible biomarkers for cancer. KLK2 and KLK3 [prostate-specific antigen (PSA)] are
used as the serum biomarker for prostate cancer.
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