Proteolysis_Biomarkers Flashcards

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1
Q

What were the first diagnostic markers used for MI?

A
  • AST
  • ALT
  • LDH
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2
Q

What is the major current diagnostic marker for MI?

A

Troponin (I and T types)

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3
Q

What types of muscle is Troponin present?

A

Skeletal and Cardiac

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4
Q

What Markers represent Liver damage?

A
  • ALT

- AST

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5
Q

What markers represent Gall bladder problems?

A
  • GGT (Gamma-Glutamyl transferase)

- Alkaline phosphatase (ALP)

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6
Q

How do troponin levels change after an MI?

A
  • levels rise 2 - 6 hours after

- Remain elevated for 4 to 10 days

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7
Q

What is the normal range for ALT?

A

5 - 40 IU/ L

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8
Q

What is the normal range for AST?

A

5 - 37 IU/ L

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9
Q

What is the normal level of ALP?

A

44 - 147 IU/L

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10
Q

Wha this the normal albumin level?

A

3.5 - 5.5 mg/dL

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11
Q

What is the normal bilirubin level?

A

0.2 - 1 md/dL

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12
Q

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

A

Alcoholic Liver Disease: AST > ALT

Other Liver Diseases: ALT > AST

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13
Q

What is characteristic of Hepatocellular Carcinoma?

A

Sudden increase in ALP and GGT

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14
Q

What product gets formed when too much alcohol is consumed?

A

Acetaldehyde

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15
Q

What is Steatosis?

A

Fat deposit in the Liver

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16
Q

Describe the pathology of Alcoholism leading to fatty liver.

A
  • Alcohol Dehydrogenase produces NADH
  • Excess NADH drives FA production
  • Fatty acids build up on liver
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17
Q

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

A
  • Acetaldehyde gets presented on surface of hepatocyte —> Neutrophilic attack
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18
Q

What is the role of alkaline phosphatase?

A

Dephosphorylates compounds in an alkaline environment

19
Q

What organs contain Alkaline phosphate?

A
  • Bone
  • Liver
  • Kidney
  • Placenta
20
Q

What are the conditions which cause low levels of alkaline phosphatase?

A
- Wilsons 
Disease
- CML
- Hypothyroidism
- Postmenopause
21
Q

What are the tissue specific ALPs?

Tissue Nonspecific?

A

Tissue specific: Placental, Intestinal, and Germ Cell

Nonspecific: Ubiquitous Bone and liver —-> TNSALP

22
Q

Where is Acid Phosphatase located?

A
  • Prostate cells
  • RBC
  • Plateletys
  • WBC
23
Q

What are normal ACP levels?

A

2.5 - 12 U/L

24
Q

What are the two main uses of ACP?

A
  • Prostate cancer progression

- High amounts in sperm —> Forensic investigation of Rape

25
Q

What enzyme is high in Pompei’s disease?

A

Acid Phosphatase (ACP)

26
Q

What are normal levels of LDH?

A

200 - 300 U/L

27
Q

What are the different locations and Isozymes of LDH? What are common associated conditions?

A

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

28
Q

What are the three isozymes of Creatine Kinase?

A

CK-mm: Skeletal Muscle

CK-BB: Brain

CK-MB: Heart and Skeletal Muscle

29
Q

What enzyme indicator is especially high in Duchene MD?

A

Creatine Kinase

30
Q

What are normal levels of Creatine in men/women?

A

Men: 15 - 100 U/L

Women: 10 - 80 U/L

31
Q

What organ displays high activity levels of Amylase and Lipase when damaged?

A

Pancreas

32
Q

What conditions commonly cause pancreatitis?

A
  1. Alcoholism
  2. Gallstones
  3. Hypertriglyceridemia
  4. Post abdominal surgery
  5. Pancreatic cancer
  6. Pancreatic duct obstruction
33
Q

4 Classes of proteolytc enzymes?

A
  • Serine
  • Thiol
  • Zinc
  • Aspartyl
34
Q

To what does plasminogen bind, and where is it located with respect to clots?

A

Fibrin and Fibrinogen

Becomes incorporated into clots

35
Q

Name 3 compounds that activate plasminogen and briefly describe them

A

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

36
Q

How does TPA function?

A
  • Slowly activates plasminogen

- Binds to fibrin and activates —> Cleaves plasminogen unto plasmin which can really dissolve

37
Q

Describe the activity of Urokinase.

A
  • Activates plasminogen in absence of fibrin
38
Q

How does the method by which streptokinase functions differ from the ways urokinase and TPA function?

A
  • NOT a Serine kinase

- forms 1:1 complexes with plasminogen

39
Q

Describe ubiquitination and the ATP dependent process of protein targeting involving ubiquitin.

A
  • 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
40
Q

What determines the half life of a protein in tissue? Example?

A

Amino Terminal residue.

Highly stable: Met, Gly, Ala, Ser, Thre, Wal

Highly Unstable: Leu, Phe, Asp, Lys, Arg

41
Q

What is the means of protein target recognition for degradation of serum proteins?

A

Ubiquitination?

42
Q

How are plasminogen activators used in therapy? What type of complication is likely to occur?

A
  • Used in treatment of coronary artery thrombosis

- Complications can include hemorrhage if hemostatic plugs are loses as well

43
Q

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?

A
  • 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