2.4 Creatine Kinase Flashcards
What is creatine kinase used for?
To convert creatine phosphate into creatine and ATP
Where in the body is creatine kinase found in particularly high concentrations?
in the brain and muscle cells
When is creatine kinase released into the circulation?
Following death/damage of brain and muscle cells
How many isoforms are there of creatine kinase?
Three isoforms which can be identified through gel electrophoresis
What are the three isoforms of creatine kinase?
MM, MB and BB
What is the only place in which the MB isoform is found?
Cardiac muscle
Which isoform moves closest to the negative electrode?
MM isoform
What is myocardial infarct?
Death of heart muscle cells
What might cause a lack of oxygen resulting in a myocardial infarct?
Blockage of the cardiac arteries (atherosclerosis)
Why do cells need oxygen, how do they use it and why do cells die without it?
ATP is generated via glycolysis, the Krebs Cycle and oxidative phosphorylation
The end point of the process requires atmospheric oxygen, hence if there is less oxygen supplied to a cell there is less ATP, pumps do not function, ion balance is lost and cells die.
Why can the levels of proteins inside the blood be used to indirectly indicate cell death?
Cellular contents are released from cells when they die
The levels of many proteins including creatine kinase and lactate dehydrogenase in serum can be used as indirect indicators of cell death
Describe the absorption spectrum for NADH and NAD+?
They are distinct
What technique is used to detect CK activity in the serum?
Coupled assay
How can increased CK be related specifically to the death of cardiac muscle rather than skeletal muscle and brain tissue?
The only tissue where both genes are expressed is cardiac muscle cells. They therefore make all three dimers including the hybrid MB form
Thus, death of cardiac muscle fibres can be determined if the MB isoform of CK can be detected in the serum
Which form of creatine kinase is only expressed in the brain?
BB isoform as the brain only expresses the B gene
Which isoform of creatine kinase is only found in skeletal muscle?
MM isoform as only the M gene is expressed
In what instance would measuring MM levels be useful?
To determine the extent of skeletal muscle damage in conditions like muscular dystrophy
What is the level of MB isoform in the serum directly proportional to?
To the amount of cell death in the heart
Is a simple measure of CK activity in serum a sufficiently good diagnostic test for myocardial infarct?
No, because the activity could be from any of three tissues
Assay of the MB form is essential (blood test then electrophoresis)
In general how might you experimentally discern between different protein isoforms, what methods can be used?
Electrophoresis or column chromatography
But both are slow and require expert operation thus not ideal in casualty department
How many hours after an heart attack is CK concentration highest?
24-48 hours after
What are the four markers for myocardial damage?
Creatine kinase
Serum glutamate oxaloacetate transaminase
Lactate dehydrogenase
Cardiac troponin
Why is cardiac troponin useful are a marker for myocardial damage?
Cardiac troponin I and troponin T are tissue specific and are not present in any other muscle
Thus their presence in serum is a specific marker for cardiac infarction
When does cardiac troponin appear in serum after infarction and how long does it persist?
After 48h of infarction
Persisting for approximately 5 days
What causes the plasma membrane of myocardial cells to become leaky?
When there is no oxygen, no oxidative phosporylation, leading to no ATP, pumps stop working, homeostatic balance is lost, so things leak out the cells
Why might the three isoenzymes be separated by electrophoresis?
CK is a dimer protein
The two monomers in CK have approximately the same molecular weight but differ in their pI (isoelectric point) thus can be separated by charge
Which corresponds to LDH, CK or SGOT?
