Antitrypsin activity

FIGURE 11.5 Degradation of N-a-benzoyl-l-arginine ethyl ester by trypsin. All three carboxyl containing polymers have antitrypsin activity, but the activity of trypsin in the presence poly(ethylene glycol) modified poly(methacrylic acid) is not greatly reduced. (Adapted from Madsen and Peppas 1999.)... 

It demonstrated in vitro antimicrobial, antifungal and anti-HIV activities [24,133], Recently, a halisulphate derivative with antithrombin and antitrypsin activity was isolated from the marine sponge Coscinoderma mathewsi [134], The absolute configuration of halisulphate has been determined by application of the chiral amide method coupled with chemical degradation procedures [135],... 

Different types of serum have been used to supplement media with various necessary growth factors and hormones that cells need for their growth. Serum also contains various adhesion factors and antitrypsin activity, which promotes cell attachment. Serum components can act as buffers and as chelators for labile or water insoluble nutrients, bind and neutralize toxins, and provide protease inhibitors. Serum can also reduce oxidative injury to cells caused by ferrous ions. Reduced serum conditions have also been reported to increase the susceptibility of cells to apoptosis. ... 

Some people have a genetic predisposition to emphysema. This is called familial emphysema. These individuals have been found to have a genetic defect in the gene that encodes the human plasma protein Uj-antitrypsin. As the name suggests, Ui-antitrypsin is an inhibitor of the proteolytic enzyme trypsin. But, as we have seen in this chapter, trypsin is just one member of a large family of proteolytic enzymes called the serine proteases. In the case of the oii-antitrypsin activity in the lung, it is the inhibition of the enzyme elastase that is the critical event. 

Peptidomimetic functionalized carbon nanotubes with antitrypsin activity. Carbon, 47, 3550-3558. 

Anti thymocyte globulin Antitrypsin Anti tuberculin agents Antitumor activity... 

Four naturally occurring thrombin inhibitors exist in normal plasma. The most important is antithrombin III (often called simply antithrombin), which contributes approximately 75% of the antithrombin activity. Antithrombin III can also inhibit the activities of factors IXa, Xa, XIa, Xlla, and Vila complexed with tissue factor. a2-Macroglobulin contributes most of the remainder of the antithrombin activity, with heparin cofactor II and aj-antitrypsin acting as minor inhibitors under physiologic conditions. 

There are a number of disorders, including cancer and shock, in which the concentrations of plasminogen activators increase. In addition, the antiplasmin activities contributed by tti-antitrypsin and a2-antiplas-min may be impaired in diseases such as cirrhosis. Since certain bacterial products, such as streptokinase, are capable of activating plasminogen, they may be responsible for the diffuse hemotthage sometimes observed in patients with disseminated bacterial infections. 

In inflammatory conditions, activated PMNs may pro-teolytically (by release of lysosomal enzymes) and oxidatively (by release of HOCl) inactivate ai-antitrypsin. Studies of synovial fluid samples from patients with RA showed that a i-antitrypsin was both cleaved and oxidized, resulting in inactivation (Chidwick et al., 1991, 1994). Free-radical attack on ai-antitrypsin and its subsequent inactivation may contribute to the destruction of joint tissues in arthritis due to the imbalance between elastase and its inhibitors. 

Chidwick, K., Winyard, P.G., Zhang, Z., Farrell, A.J. and Blake, D.R, (1991). Inactivation of the elastase inhibitory activity of ai-antitrypsin in fresh samples of synovial fluid from patients with rheumatoid arthritis. Ann. Rheum. Dis. 50, 915-916. 

The protective antiprotease -antitrypsin (AAT) inhibits several protease enzymes, including neutrophil elastase. In the presence of unopposed AAT activity, elastase attacks elastin, which is a major component of alveolar walls. A hereditary deficiency of AAT results in an increased risk for premature development of emphysema. In the inherited disease, there is an absolute deficiency of AAT. In emphysema resulting from cigarettesmoking, the imbalance is associated with increased protease activity or reduced activity of antiproteases. Activated inflammatory cells release several other proteases, including cathepsins and metalloproteinases. In addition, oxidative stress reduces antiprotease (or protective) activity. 

Vemuri et al.17 looked at the effects of various cryoprotectants, freezing rates, and buffer systems on the shelf-life of lyophilized recombinant alphar antitrypsin (rAAT). Alpharantitrypsin (AAT) is labile in solution therefore, a more stable presentation was required. A competitive ELISA was used to measure total AAT in a sample. The AAT in the sample competed with HRP-labeled AAT for binding to the specific antibody. A stable formulation containing lactose as a cryoprotectant was found that maintained the protein s specific activity. 

Qu D. Teckman )H, Omura S, Perlmutter DH (1996) Degradation of a mutant secretory protein, a 1-antitrypsin Z, in the endoplasmic reticulum requires proteasome activity. J Biol Chem 271 22791-22795 Rapoport TA, Jungnickel B, Kutay U (1996) Protein transport across the eukaryotic endoplasmic reticulum and bacterial inner membranes. Annu Rev Bioi em 65 271-303... 

Antitrypsin (AAT). The ai-antitrypsin (AAT) level in serum is one of the nonspecific markers of the activity of various tumors. Studies discuss the importance of evaluation of the AAT level in CSF in patients with various CNS... 

Erythropoietin Thrombopoietin Tissue plasminogen activator -Antitrypsin... 

Varley, J Birch, J. (1999). Reactor design for large scale suspension animal cell culture. Cytotechnology 29(3), 177-205. Wright, G. et al. (1991). High level expression of active human -antitrypsin in the milk of transgenic sheep. Bwj Technology 9, 830-834. 

Wright, G. et al. (1991). High level expression of active human a-1-antitrypsin in the milk of transgenic sheep. Bioj... 

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