Inter-a-trypsin inhibitor

The plasma peptide component from 10 melanoma and healthy individuals was examined by a combination of RP-HPLC, SEEDI-TOF-MS, and tandem MS. Fibrinogen a and inter-a-trypsin inhibitor heavy chain H4 fragments were absent in tumor samples [106]. 

Inter-a-trypsin inhibitor 160 Unknown None known... 

There appears to be sequence homology between the pineapple stem bromelain inhibitors and some of the small molecular weight inhibitors from the legumlnosae (91) Human inter-a-trypsin inhibitor contains two domains with great similarity to the domains of the Kunitz-type inhibitors (44 92-94)> The ovoinhibitors from Japanese quail and chicken egg whites contain six tandem domains which are homologous to the Kazal pancreatic secretory inhibitor and to the ovomucoids (69) ... 

Fraser et al (1972) showed 25 years ago that addition of various serum proteins to hyaluronan substantially increased the viscosity and this has received a renewed interest in view of recently discovered hyaladherins (see above). The TSG-6 and inter-a-trypsin inhibitor and other acute phase reactants such as haptoglobin are concentrated to arthritic synovial fluid [52], It is not known to what extent these are affecting the rheology and lubricating properties. 

Hutadilok N. Ghosh P, Brooks PM. Binding of haptoglobin, inter-a-trypsin inhibitor, and 1 proteinase inhibitor to synovial fluid hyaluronate and the influence of these proteins on its degradation byoxygen derived free radicals. Ann Rheum Dis. 1988 47 377-85. 

Another unusual hyaluronan-binding protein is inter-a-trypsin inhibitor [30]. This serum protein is composed of a light ehain, also known as bikunin, and two heavy chains which are covalently cross-bridged by chondroitin sulfate. Hyaluronan can replace chondroitin sulfate by trans-esterification or bind non-covalently to the heavy chains. This interaction has been shown to bind hyaluronan to cell surfaces [30] and to participate in forming a matrix around the oocyte during ovulation [31, 32). 

Another interesting system in which hyaluronan plays an important role is expansion of the cumulus oophorus during ovulation. In response to follicle stimulating hormone and a factor produced by the oocyte, hyaluronan synthesis by the cumulus cells surrounding the oocyte increases dramatically [32], A stable, gel-like matrix is formed between the cumulus cells due to crosslinking of hyaluronan by inter-a-trypsin inhibitor and TSG-6 [31, 32]. This matrix is responsible for the integrity of the cumulus cell-oocyte complex which is required for protection and transport of the oocyte during ovulation, entry into the oviduct and fertilization. Sperm-associated hyaluronidases allow penetration of this matrix at fertilization. 

Huang L, Yoneda M, Kimata K. A serum-derived hyaluronan-assodated protein (SHAP) is the heavy chain of the inter a-trypsin inhibitor. J Biol Chem 1993 268 26725-26730. 

Chen L, Mao SJT, McLean LR, Powers RW, Larsen WJ. Proteins of the inter-a-trypsin inhibitor family stabilize the cumulus extracellular matrix throt their direct binding with hyaluronic acid. J Biol Chem 1994 269 28282-28287. 

Hyaluronan also occurs covalently bound to proteins such as inter-alpha trypsin inhibitor, a plasma protein that also functions as a stabilizer of HA-rich structures,21,22 such as the cumulus mass surrounding the mammalian ovum.23... 

Cuvelier, A. et al., Proteins of the inter-alpha trypsin inhibitor (ITI) family. A major role in the biology of the extracellular matrix, Rev. Mai. Respir., 17, 437, 2000. 

Bost F, Diarra-Mehrpour M, Martin JP. Inter-alpha-trypsin inhibitor proteoglycan family—a group of proteins binding and stabilizing the extracellular matrix. Eur J Biochem 1998 252 339-346. 

Janssen U, Thomas G, Giant T, Phillips A. Expression of inter-alpha-trypsin inhibitor and tumor necrosis factor-stimulated gene 6 in renal proximal tubular epithelial cells. Kidney... 

Inbibin (activin), beta A Inhibin (activin), beta B Inbibin (activin), beta C Inhibin (activin), beta E Inhibin, alpha Insulin C-peptide Insulin, A chain Insulin, B chain Insulin-like growth factor lA Insulin-like growth factor II Inter-alpha trypsin inhibitor, HI Inter-alpha trypsin inhibitor, H2 Inter-alpha trypsin inhibitor, H4 Inter-alpha trypsin inhibitor, L Interferon alpha Interferon beta Interferon gamma Interleukin-1 beta Interleukin-10 Interleukin-12, alpha Interleukin-12, beta Interleukin-1 receptor antagonist Interleukin-2 Interleukin-4... 

Using this approach, Bizzozero and Zweifel (9) and Bizzozero and Dutler (10) have constructed molecular models of two intermediates (an enzyme-substrate complex and a tetrahedral intermediate) by appropriate modification of the models of stable enzyme-species. The stable enzyme-species used (15. 15) are trypsin-benzamidine complex (TR-B) (17), trypsin-pancreatic trypsin inhibitor complex (TR-PTI) (18, 19) and tosyl-chymotrypsin (Tos-CHT) (20) which are related to enzyme substrate complex, tetrahedral inter-mediate and acyl-enzyme respectively. 

---