Plasma Proteins and Immunoglobulins ppt Flashcards
Equation that illustrates of hydrostatic and oncotic forces in the movement of fluid across capillary membranes.
Starling Equation
T/F: There is a net outward force in the arteriolar end
True
Note: Blood pressure in the arterioles is higher than the oncotic pressure, hence, the movement of fluid from outward of the arteriolar lumen.
T/F: Gamma-globulins are synthesized in the liver
False
Most plasma proteins are synthesized in the liver except:
gamma-globulins (aka immunoglobulins) = lymphocytes
von Willebrand factor = vascular endothelium
Which characteristic/s of plasma proteins is/are FALSE?
- Mostly synthesized in the liver
- Most are lipoproteins
- Many exhibit polymorphism.
- Each plasma protein has a characteristic halflife
in the circulation.
- Many act as acute phase proteins
- Produced by cytosolic ribosomes
2 and 6 are False.
- Most Plasma proteins are GLYCOPROTEINS except albumin.
- Plasma proteins are synthesized in RER
Albumin has the ff properties, EXCEPT?
A. Major protein of human plasma (60% of plasma proteins)
B. 60% of albumin in plasma and 40% in interstitial space
C. Low molecular weight and high concentration
D. Account for ~75-80% of OSMOTIC pressure
E. Binds various ligands (eg. FFA, calcium, some steroid hormones, bilirubin); transport copper and various drugs
B is False.
60% of albumin occurs in the extracellular space while 40% is in plasma
Matching Type:
- Transports iron around the body
- Binds extracorpuscular Hb
- Stores iron
- Transfers ferrous iron from lumen to enterocyte
- Binds transferrin to cells for endocytosis
- Transfers iron across the enterocyte basolateral membrane
a. Ferritin
b. Transferrin
c. DMT1
d. Transferrin Receptor 1 (TfR1)
e. Ferroportin
f. Haptoglobin
- Transports iron around the body- transferrin
- Binds extracorpuscular Hb - haptoglobin
- Stores iron - ferritin
- Transfers ferrous iron from lumen to enterocyte - DMT1
- Binds transferrin to cells for endocytosis- TfR1
- Transfers iron across the enterocyte basolateral membrane - ferroportin
Downregulates intestinal iron absorption by inhibiting ferroportin via internalization and degradation
Hepcidin
Ferrous iron in the enterocytes is turned to ferric iron to allow for transferrin transport. This conversion is mediated by a ferroxidase called?
Hephaestin, a copper-containing ferroxidase (enterocytes). In macrophage, the ferroxidase is ceruloplasmin
How do high levels of iron alter ferritin and TfR synthesis? (enumerate pathway)
- High levels of iron
- Iron binds to IRE-BP (iron response element-binding protein) aka Iron Regulatory Protein (IRP)
- IRE fails to bind to mRNA
- Ferritin synthesis increases while TfR decreases
- Iron is stored in ferritin
- Normal iron levels
Feedback mechanism of low iron levels (enumerate pathway)
- low iron
- no iron will bind to IRE-BP
- IRE is free to bind to mRNA
- Ferritin is inactivated while TfR synthesis is increased
TfR1 and TfR2 are iron receptors that mediate iron endocytosis for incresed absorption
- Iron level normalizes
Carries up to 90% of copper in the plasma with each protein carrying 6 copper atoms
Ceruloplasmin
Note: “cerulean” means sky. Ceruloplasmin is blue in color due to high copper content
Copper is a cofactor to many enzymes. Match the enzyme to their function:
- Cytochrome c oxidase
- Ceruloplasmin
- Tyrosinase
- Lysyl oxidase
- Superoxidase dismutase
a. protect against oxidants
b. connective tissue synthesis
c. cellular respiration
d. iron hemostasis
e. melanin formation
Cytochrome c oxidase – cellular respiration
Ceruloplasmin – iron hemostasis
Tyrosinase – melanin formation
Lysyl oxidase – connective tissue synthesis
Superoxidase dismutase – protect against oxidants
Kinky or Steely hair disease due to a defect in copper efflux from cells.
Menke’s Disease
Notes: X-linked, only males are affected; mutation in ATP7A gene for copper-binding P-type ATPase.
Genetic disease wherein copper cannot be excreted from the bile and so accumulates in the liver, brain, kidney and RBC.
Wilson’s Disease
Note: Due to mutation in the gene for a copper-binding P-type ATPase (ATP7B)
Increase in level of copper in liver cells inhibit coupling to apoceruloplasmin which leads low ceruloplasmin in plasma
Copper toxicosis
A clinical finding in Px with Wilson’s Disease wherein there is a green or gold pigment around the cornea due to deposition of copper in the Descemet’s membrane
Kayser-Fleischer ring
Extra: si Georgina Wilson kay Gold ang mata
Treatment of Wilson’s disease is a diet low in copper and administration f a copper-chelating agent called
Penicillamine
The principal serpin (SERine Protease INhibitor) in human plasma which inhibits trypsin, elastase, and other serine proteases.
alpha1-antiproteinase (formerly alpha1-antitrypsin).
Note: They are synthesized by hepatocytes and macrophage
Deficiency in a1-antiproteinase has been linked witha. lung condition called:
Emphysema
Note: Without a1-antiproteinase, elastase will not be inhibited. Elastase degrades lung alveoli leading to emphysema.
Smoking oxidizes what amino acid residue of the protease-bindong site of a1-antiproteinase?
Methionine (specifically Met358)
Pathway: Smoking oxidizes methionine rendering the a1-antiproteinase unable to neutralize serine proteases that destroy alveoli.
A large plasma glycoprotein synthesized by monocytes, hepatocytes, and astrocytes that acts as a panproteinase inhibitor
alpha2-macroglobulin
Note: Comprises 8-10% of total plasma protein
The ff are function of a2-macroglobulin, EXCEPT:
A. Transport of 10% of zinc in plasma
B. Major member of plasma proteins that include complement proteins C3 and C4
C. Binds many cytokines (PDGF, TGF b, etc) and targets them toward particular tissues
D. Inhibits specific proteases
D is FALSE. As a panptoteinase, a2-macroglobulin acts as a broad-spectrum protease inhibitor
An impairment of tissue function that leads to the accumulation of various insoluble fibrillar proteins in the interstitial spaces between cells of tissues.
Amyloidosis
Note: the term is a misnomer because it was origially thought that starch-like fibrils accumulate in interstitial spaces. Later, it was found out that it was the accumulation of plasma proteins in beta-pleated sheet conformation