Exam 2- Proteolysis Flashcards
The 4 major classes of proteolytic enzymes
1) Serine
2) Thiol
3) Zinc
4) Aspartyl
To what does plasminogen bind, and where is it located with respect to clots?
Plasminogen binds to both fibrin and fibrinogen and becomes incorporated into clots as they form
Name 3 compounds that activate plasminogen
Tissue plasminogen activator- synthesized in endothelial cells following damage to blood vessels.
Urokinase-found in the urine activates plasminogen in the absence of fibrin
Streptokinase- isolated from streptococci. I
How does TPA function?
TPA works by binding to fibrin and cleaving plasminogen in a clot, which gives plasmin which cleaves the clot into soluble products
Describe the activity of urokinase
It activates plasminogen in the absence of fibrin
It is secreted by epithelial cells lining renal tubules and it is believed to be involved in lysing fibrin in these ducts
How does the method by which streptokinase function differ from the ways that urokinase and TPA function?
Streptokinase is not a serine protease. It forms a 1:1 complex with plasminogen in the fluid phase, exposing the active site
Describe ubiquitination
Ubiquitin gets attached to intracellular proteins and marks them for degradation
After a few initial reactions the carboxy-terminal glycine of ubiquitin becomes covalently attached to the epsilon-amino group of lysine residues of proteins that are to be degraded
Subsequent to ubiquitination, the protein is translocation to a proteosome lined by proteolytic enzymes that have chymotrypsin-like, trypsin-like, and peptidyl glutamyl hydrolyzing activities that destroy the protein into fragments
What determines the half-life of a protein in a tissue?
Amino-terminal residue
Describe the means of protein target recognition and ATP independent degradation of circulating/serum glycoproteins.
A protein loses sialic acid residues from the non-reducing end and is so marked for degradation. They are recognized by liver asialo-glycoproteins receptors and internalized where they are degraded in lysozymes by proteases called cathepsins
How are plasminogen activators used in therapy? Complications?
Thrombolytic therapy to restore the potency of coronary arteries after thrombosis. If given early enough, can reduce mortality after an MI (< 6 hrs). Preserve function of myocardium.
The danger is that it might degrade a hemostatic plug, and cause hemorrhaging
What roles do proteases play in the pathogenic process in cancer?
In cancer, tumors often secrete special proteases known as metallo-proteases which have metal ions such as zinc at their active site that can break down blood vessel walls and the extracellular matrix to allow tumor cells to metastasize
What role do proteases play in AIDS?
A viral protease known as aspartyl proteases must cleave polyprotein structures in order for infected cells to spread virions
What kinds of protease inhibitors are used for AIDS therapy?
Specific aspartyl protease inhibitors such as Sequinovir and Ritonavir
