B Module tutorial - Proteins and Enzymes
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Status: v103 Time: 2025-03-16 Tags: tutorial Links:
Todo:
Content:
Objectives:
- Outline the function of major plasma proteins
- Explain the significance of elevated and or diminished levels of total protein albumin a1 antitrypsin
- Eescribe the basic structure of the immunoglobins
- Outline the factors that affect the plamsa levels of enzymes
- Identify how measurement of plasma enzyme activities and or amount of specific proteins in the plama may be used in the diagnosis of disease of various body systems
- Relate disease states to chanfes in
- alkaline phosphate
- alanine and aspartate aminotransferase
- lactate dehydrogenase
- gamma gluramyltransferase
- creatine kinase
- lipase
- troponins
Objective q+a
Objectives:
- Outline the function of major plasma proteins
albumin
Alpha globin a1 antitrypsin disables elastase which reduces collateral damage by neutrophils a2 macroglobulin protease inhibitor like haptoglobulin binds free haemoglobin
beta globin transferrin plamsogen IgA antibody can show up on b band b lipoprotein (ldl)
gamma globin mostly immunoglobins and esp IgG IgM
-
Explain the significance of elevated and or diminished levels of
- total protein
- albumin
- can alter substance transport and cause oedema / sodium retention
- a1 antitrypsin
- indicates inflammation or genetic mutation and can lead to early emphysema
-
Describe the basic structure of the immunoglobins 2 light chains 2 heavy chains
-
Outline the factors that affect the plamsa levels of enzymes synthesis clearing cell turnover
-
Identify how measurement of plasma enzyme activities and or amount of specific proteins in the plama may be used in the diagnosis of disease of various body systems increased or decrease amounts of certain proteins can be related to cell turnover changes
-
Relate disease states to changes in alkaline phosphate bone changes alanine and aspartate aminotransferase liver disease sometimes infarct aspertate is elevated in infarction and
lactate dehydrogenase liver or kidney disease gamma gluramyltransferase alcohol obyse creatine kinase brain heart liver or muscle damage isoform can point in the right direction lipase
troponins myocardial infarct
content
Take home:
Rambles: the normal activity of cell leads to the release of solutes and compounds which are usually proportional to cell number
by testing concentrations we can see if there are changes in macrocell activity
serum is plasma with no coagulation factors, all the platelets WBC and rbc clotted out
sometimes the tests require serum rather than plasma
reference intervals defined as 2 reference intervals from the population healhty mean (95% of population will fall in the reference interval)
sometimes an abnormal result is barely significant sometimes its extremely severe
time course and severity you cannot rely on a single reading to inform of severity ot presence of a disease eg reading a little above normal could signify acute condition in the past or current chronic condition
different proteins in blood can be have different halflives and decrease more rapidly
isoenzymes isoenzymes are different structural variants of the same enzyme which catalyse the same reaction but may be produced in different cells in different tissues CK-MM is skeletal muscle CK-BB is brain CK- MB is heart
plasma proteins
albumin - hydrophobic transport protein and major contributor to oncotic pressure
globulins. “globular proteins” soluble in saline but not water alpha - a1 a2 band proteins like a1antitrypsin a2 macroglobin haptoglobin beta b1 and b2 band protien like transferrin plasmogen igA b lipoprotein (ldl) gamma mostly immunoglobulins coagulation protein not presetn in serum protein electrophoresis
position on the elecrophoretogram is based on protein charge Serum protein electrophoresis
albumin may indicate loss of albumin (burns nephrotic syndrome) reduced production of albumin or health status increase in albumin may indicate haemoconcentration (dehydration) may aslo seperate into different peaks with congenital condition
a1 decrease a1antitrypsin decreased globulin production in liver neprotic syndrome
increase acute inflammation or malignancy
a2 increase can mean inflammation or in the accumulation of the a2macroglobulin in nephrotic syndrome
haemolysis can cause haemoglocin haptoglobin complexes to appear as a distinct peak in the a2-b interzone along decrease a2 peak
B1 increase increased transferrin from iron deficientcy anaemia pregnancy or oestrogen therapy
B2 Increase inflammation / more complement proteins
Decrease Autoimmune disease which can activate and deplete compliment
when fibrinogen is present it can show inb the b2 band
y hyper gammaglobulinaemia cirrosis inflammation hypo/agammaglobulinaemia other things
SPE is mostly useful for major protein groups Examples plasma cell myeloma narrow peak in y region consistent with para protein production
rest of the y region is low reduction of albumin is found in most patients with plasma cell myeloma particularly in those with significent proteinuria
nephrotic syndrom is decrease in alb an y proteins but increase in a2 protein band
this is bc of proteins lost to urine while simultaneously making more proteins a2 macroglobulin is too big to be lost and therefore accumulates
cirrhosis reduction in albumin and increase in y globulins due to liver not filtering out toxins
alternate methods colourimetric assay enymatic assay immunological assay
interpreting test results
| Protein / enzyme | Tissue Location | pathophysiology | |
|---|---|---|---|
| alanine aminotransferase | produced in most tissues in small amounts and in the liver in high amounts | elevated in hepatocellular damage | |
| aspartate aminotransferase | produced in same tissues as alt but highly in rbc muscle tissue and others | elevated in hepatocellular damage, haemolysis, myocardial infarction | |
| alkaline phosphatase | produced in high amount in liver bone placenta and intestinal epithelium | elevated in hepatobiliary damage bone disease | |
| Gamma glutamyl transferase | high amounts liver kidnet and pancreas | elecated in hepatobiliary damage | |
| lactate dehydrogenase | produced in many tissues particularly muscle rbc liver pancreas and kidneys | elevated in many pathologies iso enzymes can be more helpful | |
| creatine kinase | produced in high amount in muscle particularly heart and skeletal muscle | elecated in myocyte damage. isoenzymes can provide specificity | |
| pancreatic lipase | pancreas | elecated in pancreatic tissue damage | |
| troponin | heart | elecated in cardiac myocyte damage |
liver significance significant ALT/AST ast:alt ratio “>2 alcoholic liver disease 1 in acute hepatitis <1 in chronic liver diasease cirrrhosis cholestasis ‘>10x url major acute hepatitis drug induced liver necrosis 5-10x url moderate cholestasis chronic hepatitis, liver hypoxia <5x url mild myocardial infarction, pancreatitis, trauma, viral infection, drug- induced (e.g. statins), post-surgery, haemolysis
GGT ‘>10 URL major 5-10x moderate <5x mild
ALP ‘>5x major <5x minor