Creatine kinase Flashcards
Where is there a high concentration of creatine kinase found?
Muscle, brain and heart cells
When is creatine kinase released into the circulation?
Following death or damage to muscle/brain cells
What is meant by dimeric and what are the three dimeric isoenzymes of creatine kinase in humans?
CK has 2 subunits/monomers (i.e. it’s a dimer) that are coded for by 2 different genes
These generate 2 different monomer isoforms- M and B
The monomers associate and bind to one another in the cytoplasm to produce active dimers
MM
MB
BB
Which dimer of CK is most common in…
- heart cells
- brain cells
- muscle cells
- Muscle cells- MM (homodimer)
- Brain cells- BB (homodimer)
- Heart cells- MB (heterodimer) (only found in myocardium)
How can the creatine kinase isoenzymes be separated?
Electrophoresis on cellulose acetate strips
How can increased CK be related specifically to the death of cardiac muscle rather than skeletal muscle and brain tissue?
The brain ONLY expresses the B gene so can only make B monomers so only makes CK-BB
The skeletal muscle cells ONLY make CK-MM
Cardiac muscle cells are the only tissue where both genes are expressed so they make all 3 dimers including CK-MB. This means death of cardiac muscle fibres can be determined if CK-MB is detected in serum
What is a myocardial infarct and what causes this to occur?
Death of heart muscle cells
lack of oxygen due to blockage of cardiac arteries, this process is termed atherosclerosis
What constitutes a cell i.e. a semi-permeable membrane separating the inside from the outside?
- There is active exclusion of some things such as Na+ ions.
- This needs a protein pump in the membrane.
- These are a type of enzyme called membrane ATPases.
- They use energy in the form of adenosine triphosphate (ATP) to pump ions.
Why do cells need oxygen?
The end point of the respiration 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.
How can you determine CK activity?
CK activity can be detected by a coupled assay leading to generation of detectable products
creatine phosphate + ADP - CK→ creatine + ATP
D-glucose + ATP – hexokinase -→ ADP + G6P
G6P + NADP+ –G6P dehydrogenase-→ 6-PG + NADPH + H+
How would you establish a diagnosis for myocardial infarction?
- Do a blood test
- Do electrophoresis to check for CK-MB (since it’s the only isoenzyme of CK found in heart tissue)
immunological approach - manufacture of antibodies against CK-MB (not used alone)
Does an increase in serum CK activity relate to the size of myocardial damage?
Yes- the levels of CK BM isoform in the serum are directly proportional to the amount of cell death in the heart
Each myocyte can be considered to be approximately of equal volume so, as each cell dies it releases a “quantum” of CK into the extracellular fluid and thence into the serum.
What is cardiac troponin and what does it show?
Cardiac troponin I and troponin T are only present in the heart
Troponinis the calcium switch in muscle.
Their presence in the serum represents a specific marker for cardiac infarction (typically appearing in the serum after 48h of infarction and persisting for approximately 5 days)
What other markers besides CK can be used for diagnosis of myocardial damage?
Serum glutamate oxaloacetate transaminase (SGOT)
lactate dehydrogenase (LDH)
Cardiac troponin
What is the time course of serum CK after a myocardial infarction?
Peaks after one day and persists till day 4
