Proteolysis_Biomarkers Flashcards by Cody Sellers

What were the first diagnostic markers used for MI?

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What is the major current diagnostic marker for MI?

Troponin (I and T types)

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What types of muscle is Troponin present?

Skeletal and Cardiac

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What Markers represent Liver damage?

- AST

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What markers represent Gall bladder problems?

GGT (Gamma-Glutamyl transferase)

- Alkaline phosphatase (ALP)

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How do troponin levels change after an MI?

levels rise 2 - 6 hours after

- Remain elevated for 4 to 10 days

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What is the normal range for ALT?

5 - 40 IU/ L

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What is the normal range for AST?

5 - 37 IU/ L

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What is the normal level of ALP?

44 - 147 IU/L

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Wha this the normal albumin level?

3.5 - 5.5 mg/dL

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What is the normal bilirubin level?

0.2 - 1 md/dL

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How do ALT and AST levels differ in types of liver disease?

Alcoholic Liver Disease: AST > ALT

Other Liver Diseases: ALT > AST

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What is characteristic of Hepatocellular Carcinoma?

Sudden increase in ALP and GGT

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What product gets formed when too much alcohol is consumed?

Acetaldehyde

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What is Steatosis?

Fat deposit in the Liver

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Describe the pathology of Alcoholism leading to fatty liver.

Alcohol Dehydrogenase produces NADH
Excess NADH drives FA production
Fatty acids build up on liver

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Besides Production of fatty liver, how does alcohol lead to liver disease?

Acetaldehyde gets presented on surface of hepatocyte —> Neutrophilic attack

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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?

1. Alcoholism 2. Gallstones 3. Hypertriglyceridemia 4. Post abdominal surgery 5. Pancreatic cancer 6. 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