lecture 5 - enzymes as biomarkers Flashcards
what are enzymes
protein catalysts
what are the definitions of enzymes
type of protein that accelerates the speed of chemical reaction
by binding to a substrate to form a complex
lowers activation energy in the reaction without being consumed, or changing equilibrium of reaction
why do we use enzymes as markers
amplification of signal over time
what are the two ways you can measure enzyme activity
stop the reaction and measure product formed (kinetic fixed time)
repeatedly measure product formation(kinetic continuous time)
what does ELIZA stand for
Enzyme-linked immunosorbent assay
what are isoenzymes
enzymes that differ in amino acid sequence yet catalyse the same reaction
what are biomarkers
biological molecules who’s concentration changes in response to a specific disease or intervention
what do biomarker lead to when in disease state
moderate or extensive tissue damage
what happens to the cardiac myocyte after SOME tissue damage
membrane ruptures
this damage can be repaired
enzyme levels are only elevated while damage persists
what happens to the cardiac myocyte after MORE tissue damage
cell dies
cellular necrosis
cell contents released
test blood for specific enzymes
what is the aetiology for cardiac disease
blockage of blood vessels supplying to the heart
what does the blockage of blood vessels lead to
deficiency of oxygen (ischemia)
what is non reversible damage that leads to cell death called
infarction
what is acute myocardial infarction
a heart attack
what does angina cause
heart pain
what is the aetiology of angina
reduced blood flow to the heart
what is the development of heart disease
- plaques form on the artery wall
- macrophages accumulate in the endothelial lining
- narrowing of the artery
- 70% reduced blood flow -> ischemia
what are the stages leading to myocardial infarction
- Tear or erosion of the plaques
- Cause an intraplaque thrombus
- Platelets accumulate to repair the damage
- Aggregated platelets break off and are swept downstream
- Aggregated platelets block downstream vessels
what is the treatment for platelet aggregation
antiplatelet
antithrombotic
what is the treatment for after clot formation
thrombolytic drugs
catheterisation and angioplasty
what are the cardiac biomarkers
aspartate amino transferase - elevated 12 hours
lactate dehydrogenase - elevated 36 hours
creatine kinase - elevated 4-6 hrs
what is the product of creatine + atp?
creatine phosphate + ADP
what are the sources of creatine kinase
skeletal muscle
brain
cardiac muscle
what can mask myocardial infarction
more skeletal muscle than cardia muscle
what is the specimen for CK anaylsis
non - hemolyzed serum
storage in refrigerator or freezer
what are the sources of error in CK analysis
sample not fresh or exposed to heat
anticoagulants such as citrate or fluoride
what is lactate dehydrogenase inhibited by
mercuric ions
what are sources of lactate dehydrogenase
heart
liver
kidney
skeletal muscle
what is the clinical significance of Lactate dehydrogenase
myocardial infarction
hemolytic conditions
malignancies
renal disease
what does troponin T do
binds to myosin
what does troponin I do
inhibit actin-myosin binding
what does troponin C have
Binding sites for ca2+
what happens in the absence of calcium
troponin prevents myosin from interaction with actin
prevents contraction
what are the advantages of troponin-tropomyosin
sensitive - able to detect cardiac troponin T and troponin I in more than 50% of individuals
better detection than CKMB/total CK
what tests are required to detect AMI
electrocardiogram
detection of enzymes released into the blood
what is rhabdomyolysis
rapid breakdown of damaged muscle tissue
what are the biomarkers for skeletal muscle
Rhabdomyolysis
Spills over into the urine
myoglobin
what are natriuretic peptides
small circular peptides (cardiac hormones) that PROMOTE loss of sodium from the kidneys
what are the key aims of future biomarkers
predicting the rupture of placques
detecting ischemia prior to cell death (necrosis)
