High-molecular weight kininogen
Encyclopedia
High-molecular-weight kininogen (HMWK or HK), also known as the Williams-Fitzgerald-Flaujeac factor or the Fitzgerald factor or the HMWK-kallikrein factor, is a protein
from the blood coagulation
system as well as the kinin-kallikrein system
. It is a protein that adsorbs to the surface of biomaterials that come in contact with blood in vivo. This protein circulates throughout the blood and quickly adsorbs to the material surfaces.
. It is 626 amino acid
s long, and weighs 88 to 120 kDa (dependent on glycosylation
). The kininogen is not enzymatically active, and functions only as a cofactor for the activation of kallikrein
and Hageman factor. It is also necessary for the activation of factor XI by factor XIIa. The histidine
-rich region (amino acids 420 to 510) participates most strongly in coagulation.
In addition to its role in blood coagulation, HMWK (just as Low-molecular-weight kininogen
) is a strong inhibitor of cysteine proteinases. Responsible for this activity are three related domains on its heavy chain.
HMWK is also a precursor of bradykinin
; this vasodilator substance is released through positive feedback by kallikrein
.
for both types of kininogens is located on the 3rd chromosome
(3q27).
protein and a prolonged bleeding time
and partial thromboplastin time
(PTT).
As in deficiency of the associated Hageman factor, there is no increased risk of bleeding.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
from the blood coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
system as well as the kinin-kallikrein system
Kinin-kallikrein system
The kinin-kallikrein system or simply kinin system is a poorly understood system of blood proteins that plays a role in inflammation, blood pressure control, coagulation and pain...
. It is a protein that adsorbs to the surface of biomaterials that come in contact with blood in vivo. This protein circulates throughout the blood and quickly adsorbs to the material surfaces.
Nomenclature
High-molecular weight kininogen is one of the kininogens, a class of proteins. As with many other coagulation proteins, the protein was initially named after the patients in whom deficiency was first observed. When the clinical data were combined, it turned out that all patients, in fact, had a deficiency of the same protein.Physiology
HMWK is one of the early participants of the intrinsic pathway of coagulation, together with Factor XII (Hageman factor) and prekallikreinPrekallikrein
Prekallikrein , also known as Fletcher factor, is a 85,000 Mr serine protease that complexes with High-molecular-weight kininogen. PK is the precursor of plasma kallikrein, which is a serine protease that activates kinins. PK is cleaved to produce kallikrein by activated Factor XII . -...
. It is 626 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s long, and weighs 88 to 120 kDa (dependent on glycosylation
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
). The kininogen is not enzymatically active, and functions only as a cofactor for the activation of kallikrein
Kallikrein
Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein has no known homologue, while tissue kallikrein-related peptidases encode a family of fifteen closely related serine proteases...
and Hageman factor. It is also necessary for the activation of factor XI by factor XIIa. The histidine
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
-rich region (amino acids 420 to 510) participates most strongly in coagulation.
In addition to its role in blood coagulation, HMWK (just as Low-molecular-weight kininogen
Low-molecular-weight kininogen
Low-molecular-weight kininogen is a form of kininogen, which has been identified in mice, guinea pigs, and whales.It is also found in humans....
) is a strong inhibitor of cysteine proteinases. Responsible for this activity are three related domains on its heavy chain.
HMWK is also a precursor of bradykinin
Bradykinin
Bradykinin is a peptide that causes blood vessels to dilate , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...
; this vasodilator substance is released through positive feedback by kallikrein
Kallikrein
Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein has no known homologue, while tissue kallikrein-related peptidases encode a family of fifteen closely related serine proteases...
.
Genetics
The geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
for both types of kininogens is located on the 3rd chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
(3q27).
Measurement
Measurement of HMWK is usually done with mixing studies, where plasma deficient in HMWK is mixed with the patient's sample and the PTT determined. Results are expressed in % of normal - values under 60% or over 140% are abnormal.Role in disease
The existence of HMWK was hypothesised in the 1970s when several patients were described with a deficiency of a class of plasmaBlood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
protein and a prolonged bleeding time
Bleeding time
Bleeding time is a medical test done on someone to assess their platelet functionThe term "template bleeding time" is used when the test is performed to standardized parameters. This makes it easier to compare data collected at different facilities....
and partial thromboplastin time
Partial thromboplastin time
The partial thromboplastin time or activated partial thromboplastin time is a performance indicator measuring the efficacy of both the "intrinsic" and the common coagulation pathways...
(PTT).
As in deficiency of the associated Hageman factor, there is no increased risk of bleeding.