Creatine Kinase Flashcards
What enzyme catalyses the hydrolysis of creatine phosphate?
What are the products?
Creatine phosphate + ADP ———> creatine + ATP
ATP)
Enzyme: Creatine Kinase
Why is creatine kinase one of the diagnostic blood tests conducted when someone (elderly) passes out?
(Links into which cells CK is esp present in)
Creatine kinase (CK) is found in high concs in muscle cells and brain cells
Following damage/death of brain/muscle cells, CK is released into the circulation
What are the 3 dimeric isoenzymes of creatine kinase?
Which form of creatine kinase is found in the myocardium? What % of total creatine kinase does this form represent in the myocardium?
How can you separate the 3 isoenzymes?
Dimeric enzymes of CK: MM, MB, BB (based on subunits M and B)
Human pericardium = only human tissue w MB form of CK, MB represents 15% of CK here, the rest being MM
3 isoenzymes can be separated by electrophoresis (on cellulose acetate strips)
-> MM moves furthest towards electrode
In what cells is CK found in high concs?
When and why is CK found in the blood? What does it indicate?
CK present in all cells at v low levels, but at high conc in metabolically active tissues, inc brain, heart and skeletal muscle
The contents of cells are released when they’re dying, as the plasma membrane of these cells become leaky, therefore CK in the blood (+ other proteins, inc lactate dehydrogenase) = direct indicators of cell death
What is a myocardial infarction? What causes it?
What leads to the direct cause of myocardial infarctions (secondary cause)?
Myocardial infarct = death of heart muscle cells, cells die due to oxygen deprivation
Hypoxia is caused by the blockage of cardiac arteries = atherosclerosis
Why do cells need oxygen?
What causes plasma membranes of myocardial cells to become leaky?
Cells need oxygen to generate ATP via glycolysis, the Krebs cycle, and oxidative phosphorylation. ATP is needed by protein pumps to pump ions across semi permeable membranes.
Therefore leaky membranes are caused by oxygen deprivation: less o2 —> less ATP —-> pumps don’t work —> ion balance lost + cells die
How can you determine CK activity?
CK activity in the serum can be detected by a couple assay —> generates detectable products (measure absorption of products)
Why can the three isoenzymes of CK be separated by electrophoresis?
Subunits/monomers M and B are coded for by different genes. The two monomers have approx same molecular (weight?) but differ in pI (isoelectric point) —> hence can be separated by charge
How can you establish a diagnosis of myocardial damage?
Brain only expresses B gene - BB form generated
Skeletal muscle only express M gene - MM form generated (useful in diagnosis of extent of skeletal muscle damage in muscular dystrophies)
Cardiac muscle = only tissue where both genes are expressed - make all three dimers inc BM form
—> if BM isoform of CK is detected in the serum —> indicates death lf cardiac muscle fibres
Does an increase in serum CK relate to the size of myocardial damage?
- > levels of CK BM isoform in serum is directly proportional to the amount of cell death in the heart
- > bc each myocyte is approx of equal volume (equal likelihood of dying independently of their size)
What other markers can be used to diagnose myocardial damage?
What is the time course of serum CK after a myocardial infarction?
Markers of myocardial damage:
- SGOT (serum glutamate oxaloacetate transaminase)
- LDH (lactate dehydrogenase)
- cardiac troponin I & T (only present in the heart)
CK conc is highest in serum within 48 hours of MI, but persists for 5 days
