Serum proteins Flashcards
Plasma
-supernatant following centrifugation of unclotted blood (about 55% of volume)
Serum
- supernatant following centrifugation of clotted blood (therefore has no clotting factors)
- separated by electrophoresis @ pH 8.6 so all proteins are anionic (no SDS)
α1 band proteins
α1 antitrypsin (inibits neutrophil elastase, >90%), α fetoprotein (similar to albumin in fetuses, cancer marker), transcortin (cortisol transporter), retionol binding protein
α2 band proteins
α2 macroglobulin (protease inhibitor, especially for plasmin and kallikren (both fibrinolysis), and thrombin (clotting)), ceruloplasmin (bind Cu, oxidize Fe), haptoglobin (bind free hemoglobin)
β band proteins
transferrrin (binds and transports Fe3+), hemopexin (binds free heme), β lipoprotein (LDLs)
γ band proteins
immunoglobins
Effect of low albumin
- increased water in interstitial space: edema
- colloid osmotic pressure is low
- congenital analbumeinemia appears normal–>use other proteins to maintain osmotic pressure
Albumin
- one of te smallest serum proteins
- anionic at pH 7.4
- regulates osmoitc pressure
- half life of 20 dyas
- not glycosylated in the hepatocyte
- non-enzymatically glycosylated in high serum glucose, used as BG marker over medium term
- non covalently bind up to 10 free fatty acids (transports free FA released by adipocytes iin fasting)
- binds hormones including thyroxine
- transports bilirubin and drugs (drugs can displace bilirubin from binding sites—>in infants leads to kernicterus)
- binds 40% of Ca2+ in blood influcenced by pH–>alkalosis decreases negative charge of albumin and predisposes to ypocalcemia (decrease in free, unbound Ca2+ in blood)
- Low albumin leads to reduced total calcium but doesn’t really affect free Ca2+ concentration
- negative acute phase reactant
Causes of reduced serum albumin
-malnutrition (low protein, kwashiorkor), severe liver damage, following burns (lost from burnt areas of skin), following chronic illness, nephrosis (albumin crosses glomerular basement membrane and is released in urine, which does not normally occur)
α1 antitrypsin
- inibits neutrophil elastase released during phagocytosis in the lung, acts in blood and alveoli
- > 90% of α1 band
- deficiency usually seen in smokers as it is in higher demand due to damage done by smoke–>contributes to development of emphysema (lack of inhibition leads to destrucion of elastin in lung)–>also critical met residue is oxized by cigarette smoke and inactivates it
- synthesized in liver
- M allele is normal, Z and S alleles are common in people with emphysema
- ZZ are at high risk of pulmonary disease and liver disease–>only 15% of normal amount secreted into blood, remaining enzyme accumulates in the liver–>liver disease in children
- tread defficiency with IV α1-AT
- positive acute phase reactant (down-regulates inflammation)
α fetoprotein
- abundant in fetal plasma, fxn similar to albumin
- fetal plasma has very little albumin
- marker for cancer of liver, ovaries, or testes
- marker for fetal abnormalities in pregnant women (high=neural tube defects, low=down syndrome)
- α1 band
Transcorin
- α1 band
- main transport protein for cortisol, binds 75% of hormone
- only unbound cortisol can enter cells, in areas of inflammation binding is reduced and more cortisol can be taken up into cells (inhibts PLA2, and reduction of COX-2 synthesis)
Retinol binding protein
- α1 band
- transports retinol (vit A) from liver to peripheral tiuses
- retinyl esters stored in liver
α2 macroglobulin
- α2 band
- protease inibitor and one of the largest serum proteins
- inhibits proteases including plasmin and thrombin
- 10x higher in nephrotic syndrome relative to other serum proteins (other proteins including albumin are lost, macroglobulin is still to large to get through)
Ceruloplasmin
- α2 band
- Cu containing enzyme oxidies Fe2+ to Fe3+
- Fe3+ can be bound by transferrin
- synthesized by liver
- Low levels in Wilson’s disease (early degradation)—>copper not attached to enzyme builds up in tissues–>Kayser-Fleisher rings in eyes
- facilitates ferritin action, which inhibits Fe uptake by microbes—>positive acute phase reactant
Haptoglobin
- α2 band
- bind free haemoglobin in circulation (from hemolysis of RBCs)
- cannon be excreted by kidneys and prevent loss of haemoglobin
- low free haptoglobin found in patients with acute hemolysis (all bound to hemoglobin)—>monitor progress of pts iwth hemolytic anemia
- prevents fe uptake by microves–>postitive acute phase reactant
Transferrin
- β globin band
- transports Fe3+ b/w intestine, liver, marrow and spleen
- each transferrin has 2 binding sites
- 1/3 of binding sites normally filled
- iron deficieny has low transferrin saturation
- iron overload had high transferrin saturation
Hemopexin
- β band
- binds free heme in blood
- prevents loss of Fe by kidneys
β Lipoprotein
-LDL has apoB-100 which is overall positively charged and is in β band of serum proteins
Acute phase proteins
- Positive: increase in response to inflammatory disorder–>stimulated by cytokines; functions include destruction or inhibition of growth of microbes, or down-regulation of inflammation
- Negative: decrease in resonse to inflammatory disorder (i.e.: albumin)
- response to injury, infection, extreme stress, burns, major crush injury, allergy, etc (i.e.: cirrhosis)
C-reactive protein (CRP)
- not normally found in blood, synthezied and released during inflammation (positive acute phase reactant)–>increases over 30,000x
- named for interaction with c-polypeptide of pneumococcus
- measured by specific test
IgM
- found in blood and lymph
- first antibody produced in response to antigen
IgG
- found in all blody fluids
- smallest but most common
- produced on repeaded exposure to antigen
- crosses placenta
IgE
- found in lung, skin, and mucous membranes
- secreted in allergic reactions
IgA
-foudn in body secretions and protects body surfaces, increases in cirrhosis
Multiple myeloma and Liver cirrosis on immunoglobulins
- multiple myeloma (plasma cell tumor) shows increase in monoclonal band of antibodies
- cirrhosis has increase in many immunoglobulins of all classes, especally IgA–>characteristic β-γ bridge
