Lecture 24: Enzymology Flashcards
Which disease is associated with increase in troponins serum?
Cardiac diseases
Isozymes
Catalyze the same biochemical reactions
Have multiple forms of the same enzyme
Have different biochemical and immunological properties and amino acid compositions
Different organs contain different isozymes
What can result from cellular injury
INCREASED levels of intracellular enzymes in serum
Creatine Kinase (CK) levels and ATP?
Whats the relationship
At high ATP levels:
-Creatine phosphate (CrP) is formed
At high CrP levels:
-ATP is formed using the ENERGY RICH CrP
(Found in heart)
Creatine Kinase (CK)
- Uses?
- Subunits?
- Isozymes?
-Injury marker
Subunits:
- B
- M
3 Iso:
- CK-BB (CK-1) –>Brain
- CK-MB (Ck-2) —>little skeletal muscle, mostly heart
- CK-MM (Ck-3) –>Mostly skeletal muscle
ALL CONTRIBUTE TO THE HEART
Time frame for serum in MI Markers
Ck-MB
LDH
Ck-MB:
-Peaks after 24 hours
LDH: (Lactate dehydrogenase)
-Peaks after 48 hours
LDH (Lactate dehydrogenase)
Isozymes
LDH-1:
-More heart than RBC
LDH-2:
-More RBC than heart
(Indicates problem if both are too high)
Normal serum levels for LDH
Mi episode serum levels for LDH
Normal
-shows low LDH-1/LDH-2 ratio
Mi Episode
- Heart LDH isozymes increase
- High LDH-1LDH-2 ratio
Mycardial infarcation
Ck levels
troponin levels
Measuring?
Def: Heart Attack
- Leads to increase of total CK and CK-MB
- Increase in total CK-MB and CK ration indicates a large area of damage to the HEART muscles
(Ck-MB/total CH ratio >6%)
(Ck-MB/total CK ratio >3% and troponins are increased)
Troponins:
Increase in cardiac troponins
Measurements:
- Electrophoresis
- RIA (Radioimmunoassay)
- Elisa (Enzyme-linked immunosorbent Assay)
Troponins?
Types?
Proteins involved with muscles contraction
Types:
1) Cardiac Troponin I:
- cTnI: Inhibition of actomyoscin ATPase
2) Cardiac Troponin T:
- cTnT: Tropomyosin binding
Advantages of measuring troponins for MI
early marker and long term marker
DISADVANTAGE: Can mask a small recurrent MI
Advantages of measuring CK-MB for MI
Early increase
Sharp peak after 1 day (Wouldn’t mask small recurrent MI)
Liver injury effects
Function tests
Membrane integrity tests
Hepatitis
-Leads to loss of function/leaky membranes
Function tests:
- Ammonium (High)
- Albumin (Reduced)
- Bilirubin (High)
Integrity Tests:
1) Alanine aminotransferase (ALT)
- Not specific for liver
- High concentration in hepatocytes
2) Aspartate aminotransferase (AST)
- High concentrations in liver and heart
Hepatitis:
-ALT > AST
Bile obstruction:
Types
Extra-hepatic:
- Bile ducts obstructed
- Ex: Gallstones, tumors
Instra-hepatic:
-Bile ducts irritated in liver cirrhosis
Alcohol Liver disease
-AST, ALT, GGT elevated
(Aspartate aminotransferase, Alanine aminotransferase, y-glutamyl transferase)
-2:1 ratio of AST/ALT or higher
(can be seen in liver cirrhosis)
Pancreatisis
Acute
Chronic
Acute:
-Gallstone blockage = increase of serum amylase, (pancreatic) lipase, ALP, and GGP (greater than 2-lipase/amylase)
Chronic:
- Cystic Fibrosis (CF)
- Hyperlipidemia
- years of abuse
- Shows less increase in serum
Alkaline Phosphatase
Where?
Normal increase
Abnormal increase?
Bone, bile ducts, placenta, intestines
Normal increase
= bone growth, natural healing of bones, pregnancy
Abnormal increase
=Paget disease, bone tumors
Prostate cancer
Liver cancer
(tests_
Prostate cancer test:
-Specific antigen test
Liver Cancer test:
-Alpha fetoprotein (Normal in fetus’s, but indicated
How to measure acute MI
-Measure Cardiac troponins (cTnI or cTnT) and CK-MB
INCREASE indicates acute MI
When does myoglobin and CK isoforms peak after an MI injury?
-Immediately (First one to peak), but short lasting
Noncompetitive Enzymes
Same KM, decreases VMAX
Allosteric enzyme and curves
-Activators = feed fwd = shift to LEFT on graph = smaller .5 km = more affinity for substrate
Feedback-Inhibitor = Shifted to the RIGHT =
leading to a larger K 0.5 = less affinity for the substrate.
SIGMODIAL CURVE
