Proteolysis_Biomarkers Flashcards
What were the first diagnostic markers used for MI?
- AST
- ALT
- LDH
What is the major current diagnostic marker for MI?
Troponin (I and T types)
What types of muscle is Troponin present?
Skeletal and Cardiac
What Markers represent Liver damage?
- ALT
- AST
What markers represent Gall bladder problems?
- GGT (Gamma-Glutamyl transferase)
- Alkaline phosphatase (ALP)
How do troponin levels change after an MI?
- levels rise 2 - 6 hours after
- Remain elevated for 4 to 10 days
What is the normal range for ALT?
5 - 40 IU/ L
What is the normal range for AST?
5 - 37 IU/ L
What is the normal level of ALP?
44 - 147 IU/L
Wha this the normal albumin level?
3.5 - 5.5 mg/dL
What is the normal bilirubin level?
0.2 - 1 md/dL
How do ALT and AST levels differ in types of liver disease?
Alcoholic Liver Disease: AST > ALT
Other Liver Diseases: ALT > AST
What is characteristic of Hepatocellular Carcinoma?
Sudden increase in ALP and GGT
What product gets formed when too much alcohol is consumed?
Acetaldehyde
What is Steatosis?
Fat deposit in the Liver
Describe the pathology of Alcoholism leading to fatty liver.
- Alcohol Dehydrogenase produces NADH
- Excess NADH drives FA production
- Fatty acids build up on liver
Besides Production of fatty liver, how does alcohol lead to liver disease?
- Acetaldehyde gets presented on surface of hepatocyte —> Neutrophilic attack
What is the role of alkaline phosphatase?
Dephosphorylates compounds in an alkaline environment
What organs contain Alkaline phosphate?
- Bone
- Liver
- Kidney
- Placenta
What are the conditions which cause low levels of alkaline phosphatase?
- Wilsons Disease - CML - Hypothyroidism - Postmenopause
What are the tissue specific ALPs?
Tissue Nonspecific?
Tissue specific: Placental, Intestinal, and Germ Cell
Nonspecific: Ubiquitous Bone and liver —-> TNSALP
Where is Acid Phosphatase located?
- Prostate cells
- RBC
- Plateletys
- WBC
What are normal ACP levels?
2.5 - 12 U/L
What are the two main uses of ACP?
- Prostate cancer progression
- High amounts in sperm —> Forensic investigation of Rape
What enzyme is high in Pompei’s disease?
Acid Phosphatase (ACP)
What are normal levels of LDH?
200 - 300 U/L
What are the different locations and Isozymes of LDH? What are common associated conditions?
LDH1/2 —> Myocardium and RBCs; Hemolytic anemia, leukemia, and MI
LDH 3/4 —> Kidney and Skeletal Muscle; Muscular Dystrophy and Kidney disease
LDH5 —> Liver and Skeletal muscle
What are the three isozymes of Creatine Kinase?
CK-mm: Skeletal Muscle
CK-BB: Brain
CK-MB: Heart and Skeletal Muscle
What enzyme indicator is especially high in Duchene MD?
Creatine Kinase
What are normal levels of Creatine in men/women?
Men: 15 - 100 U/L
Women: 10 - 80 U/L
What organ displays high activity levels of Amylase and Lipase when damaged?
Pancreas
What conditions commonly cause pancreatitis?
- Alcoholism
- Gallstones
- Hypertriglyceridemia
- Post abdominal surgery
- Pancreatic cancer
- Pancreatic duct obstruction
4 Classes of proteolytc enzymes?
- Serine
- Thiol
- Zinc
- Aspartyl
To what does plasminogen bind, and where is it located with respect to clots?
Fibrin and Fibrinogen
Becomes incorporated into clots
Name 3 compounds that activate plasminogen and briefly describe them
TPA —> Finger domain like fibronectin; serine protease domain; Upon binding fibrin, cleaves plasminogen in clot which yields soluble products
Urokinase —> Serine protease and readily activates in absence of fibrin; Lysis of products in urinary system
Streptokinase —> isolated f/m streptococci; NOT a serine kinase, forms 1:1 complex with plasminogen allowing proteolytic activity to be expressed
How does TPA function?
- Slowly activates plasminogen
- Binds to fibrin and activates —> Cleaves plasminogen unto plasmin which can really dissolve
Describe the activity of Urokinase.
- Activates plasminogen in absence of fibrin
How does the method by which streptokinase functions differ from the ways urokinase and TPA function?
- NOT a Serine kinase
- forms 1:1 complexes with plasminogen
Describe ubiquitination and the ATP dependent process of protein targeting involving ubiquitin.
- The carboxy-terminal glycine Of ubiquitins covalently attaches to the Epsilon amino group of lysine residues of proteins that are to be degraded
- After ubiquitination, protein is translocated to cylindrical proteosome
- Enzymes inside proteosome degrade protein
What determines the half life of a protein in tissue? Example?
Amino Terminal residue.
Highly stable: Met, Gly, Ala, Ser, Thre, Wal
Highly Unstable: Leu, Phe, Asp, Lys, Arg
What is the means of protein target recognition for degradation of serum proteins?
Ubiquitination?
How are plasminogen activators used in therapy? What type of complication is likely to occur?
- Used in treatment of coronary artery thrombosis
- Complications can include hemorrhage if hemostatic plugs are loses as well
What role do proteases play in the pathogenic process in cancer? What role do they play in AIDS? What type of inhibitors are used in AIDS treatment?
- In cancer, Tumors often secrete special proteases known as matrix metal lo-proteases
- AIDS, a viral protease of aspartyl proteases cleave polyprotein strictures which cause the spread of the virions
- Antiprotease inhibitors are used in AIDS treatment
