Creatine kinase Flashcards
Where is creatine kinase most abundant
CK is present in all cells at very low levels but is at high concentrations in metabolically very active tissues including the brain, heart and skeletal muscle.
When is creatine kinase released into circulation
Following death or damage to cells
Creatine kinase reaction
Three dimeric isoenzymes of ck in humans and how are they separated
The two different subunits M and B provide the following isoenzymes: MM, MB and BB. The only human tissue where the MB form is found is the myocardium, where MB represents about 15% of total creatine kinase, the rest being MM.
The three isoenzymes can be separated by electrophoresis on cellulose acetate strips
Myocardial infarction
Death of heart muscle cells, due to lack of O. Lack of O because of blockage of cardiac arteries in process of atherosclerosis.
Why does cell need O
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.
- How is ATP generated? Via glycolysis, the Krebs Cycle and eventually 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 is ck expelled from cell when cell is damaged or dies
Cell contents are released when they are dying, i.e. proteins that should be held inside against concentration gradients appear in the serum.
Therefore the levels of many proteins including creatine kinase (many others as well such as lactate dehydrogenase) in serum can be used as indirect indicators of cell death.
How might you determine CK activity
CK activity in the serum can be detected by a coupled assay (left) leading to the generation of detectable products.
How then can increased CK be related specifically to the death of cardiac muscle rather than skeletal muscle and brain tissue?
CK is made from two subunits or monomers i.e. it is a dimer.
The two monomers are coded for by two different genes.
These generate two different monomer isoforms “B” and “M”, have same molecular weight but differ in their pI
Monomers associate and bind to one another in the cytoplasm to produce active dimers
So if both genes are expressed in a cell, three final dimers are possible, “BB”, “MM” and “MB”.
The Brain only expresses the B gene and hence makes only B monomers and so only the BB form can be generated.
Conversely the MM form is the only one made in skeletal muscle cells (useful in diagnosis of the extent of skeletal muscle damage in muscular dystrophies).
The only tissue where both genes are expressed is cardiac muscle cells. They therefore make all three dimers including the hybrid BM form.
Thus, death of cardiac muscle fibres can be determined if the BM isoform of CK can be detected in the serum.
Do levels of ck indicate amount of cell death
levels of CK BM isoform in the serum are directly proportional to the amount of cell death in the heart. This is because each myocyte can be considered to be approximately of equal volume (they have equal likelihood of dying independently of their size) so, as each cell dies it releases a “quantum” of CK into the extracellular fluid and thence into the serum.
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 BM form is essential.
