Creatine Kinase and Myocardial Infarction Flashcards
What is an MI?
Death of heart muscle cells
Why do the cells die?
Lack of oxygen due to blockage of the cariac arteries.
Why do the cells die without oxygen?
Cells have a semi-permeable membrane separating the inside from the outside.
There is acctive exclusion of molecules such as Na+ which requires membrane ATPase pumps.
They use energy in the form of ATP to pump ions.
The end point of ATP synthesis requires atmospheric oxygen.
This means lack of oxygen prevents pumps working therefore losing ion balance.
What makes creatine kinase leak out of cells?
Cell contents are released when cell death occurs due to damage of the cell membrane.
Where are there high levels of creatine kinase and why?
Heart and skeletal muscle and the brain as they require lots of ATP.
How is creatine kinase activity determined?
Coupled assays
What molecule is detected when detecting creatine kinase? What reactions produce it?
NADPH as it absorbs UV.
Creatine phosphate + ADP -> Creatine + ATP
ATP + D-glucose -> glucose-6-phosphate + ADP
G6P + NADP+ -> 6-PG + NADPH + H+
What are the different isoforms of creatine kinase?
Two different monomers coded for by different genes. Dimers are formed.
MM = skeletal muscle
BB = brain
MB = cardiac muscle
Do the levels of BM creatine kinase relate to the amount of cell death?
The levels of BM are directly proportional to the amount of cell death as each myocyte is the same size and contains a quantum of CK.
How do the different isoforms differ?
They have approximately the same molecular weight but different pl (isoelectric point).
What technique is used to separate the isotypes in electrophoresis? Explain this process.
Isoelectric focussing.
Enzymes placed in gel which is positive at one end and negative at the other.
Isoenzyme moves to where its net charge is zero - its isoelectric point.
Explain the time course of creatine kinase.
CK peaks at 24 hours after the MI.
Time frame is 30 mins - 2.5 days.
What other markers are there of MI?
SGOT - peaks as CK decreases.
Lactate dehydrogenase - peaks after 6 days.
Troponin - appears after 2 days, lasts 5 days