Plasma kallikrein

Plasma kallikrein is a serine protease enzyme that plays a crucial role in the kinin-kallikrein system, which is involved in various physiological processes including blood coagulation, inflammation, and blood pressure regulation. Plasma kallikrein is encoded by the KLKB1 gene in humans.

Structure and Function

Plasma kallikrein is synthesized in the liver as a precursor protein known as prekallikrein. It circulates in the blood in an inactive form and is activated by Factor XII (Hageman factor) to form active kallikrein. Once activated, plasma kallikrein cleaves high-molecular-weight kininogen to release bradykinin, a potent vasodilator that increases vascular permeability and induces pain.

Role in Blood Coagulation

Plasma kallikrein is an important component of the intrinsic pathway of blood coagulation. It activates Factor XII, which in turn activates Factor XI, leading to the formation of a fibrin clot. This pathway is essential for the proper formation of blood clots and prevention of excessive bleeding.

Role in Inflammation

In addition to its role in coagulation, plasma kallikrein is involved in the inflammatory response. The bradykinin produced by kallikrein activity causes vasodilation and increased permeability of blood vessels, facilitating the movement of immune cells to sites of injury or infection. This process is critical for the body's defense mechanisms against pathogens.

Clinical Significance

Dysregulation of plasma kallikrein activity can lead to various medical conditions. Overactivity of plasma kallikrein is associated with hereditary angioedema, a condition characterized by recurrent episodes of severe swelling. Conversely, deficiencies in plasma kallikrein can result in a rare bleeding disorder known as prekallikrein deficiency.

Related Proteins and Pathways

Plasma kallikrein is part of a larger family of serine proteases that includes tissue kallikrein and other members of the kallikrein-related peptidase family. It interacts with several other proteins and pathways, including the complement system and the renin-angiotensin system.

Research and Therapeutic Applications

Research into plasma kallikrein and its inhibitors is ongoing, with potential therapeutic applications for conditions such as hereditary angioedema, hypertension, and inflammatory diseases. Inhibitors of plasma kallikrein are being explored as treatments to prevent excessive inflammation and coagulation.

See Also

• Kinin-kallikrein system
• Bradykinin
• Factor XII
• Blood coagulation
• Inflammation
• Hereditary angioedema