Sunday, March 30, 2014

Biochemistry: Plasma Proteins

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An excerpt of the lecture note:

Plasma (혈장) vs. Serum (혈청):

MW 66,000, small size considering its MW. Round and very dense. Single polypeptide: 17 disulfide bonds. Simple structure. Net charge is -18. Globular protein. pI 4.7.
Made in liver and has low viscosity, which is good for blood circulation.
60% in normal plasma. 40% go to intravascular system (blood) and 60% go to skeletal muscle (intestine)
1.    Osmotic pressure regulation of blood. Size is small but numerous in blood compared to other proteins. Responsible for 75-80% intravascular osmotic pressure, even though it composes 60% of blood. Low levels of albumin can cause edema. If there is edema, need to insert albumin. BSA (Bovine Serum Albumin), which is similar to human albumin, can be injected to prevent edema.
2.    Transport and distribution:
a.   Lipid: is insoluble so binds with albumin. (fatty acid, cholesterol, phospholipid, lipoprotein)
b.   Bilirubin: binds with albumin in liver (conjugation) to make it soluble
c.    Other: regulates concentration of Ca+, hormone (steroid), tryptophan, etc.
d.   Drugs: Abumin binds to drugs to become soluble in blood. Sulfonamide (antibiotics), dicoumarol/warfarin (anticoagulant), aspirin, penicillin G.

Alpha globulin:
1)    Alpha-fetoglobulin: very low concentration in adults. If found in high levels, reasons may be hepatoma, hepatitis (liver cirrhosis) or pregnancy. Smokers have a high concentration because of oxygen demand.
2)    Retinol binding protein (binds with Vitamin A, retinol): MW 21,000. Circulates in the form of transthyretin glycoprotein.
3)    Ceruplasmin: copper binding protein. Copper concentration regulator. It is thought that it works with feroxidase in the process of converting ferrous Fe+2 à Fe+3. If ceruloplasmin concentration is low, free form of copper concentration increases, causing copper deposition in retina of eye, basal ganglia (brain), liver. Can cause Wilson’s disease (in retina à blindness), Liver cirrhosis, Parkinson’s disease (basal ganglia). Wilson’s disease is when there is green gold pigment around cornea: Kayser-Fleisher Ring.
4)    Haptoglobulin: hemoglobin binding protein that forms 1:1 complex. Prevents hemoglobin from being excreted through kidney. If haptoglublin level drops, free form HB increases and can cause renal damage and intravascular hemolytic anemia.
5)    Protease inhibitors (7): protein hydrolysis inhibitor à prevents unwanted proteolysis.
a.   Alpha 1-antitrypsin: prevents trypsin cleavage at the Arg and Lys sites (congenitally found in emphysema, susceptible to liver disease)
b.   Alpha1-antichymotrypsin
c.    Alpha2-antiplasmin: anticoagulant (inhibits fibrinolysis)
d.   Alpha2-macroglobulin
e.   Antithrombin III
f.     Alpha-inactivator
g.    Inter alpha-trypsin inhibitor 

Beta globulin: pI 5.5
1.    Transferrin: Binds to Fe2+ (ferric) in 1:2 ratio as storage form. 3% of all plasma protein. 33% of transferrin is bound to Fe (saturation). Iron deficiency anemia is the most common anemia occurring in pregnancy because transferrin increases, which decreases free form Fe, resulting in iron defeciency. Fe deficiency can also occurs during menstruation.
2.    Hemopexin: Heme binding protein 1:1 complex. Prevents heme to be released through urinary excretion, thus preventing renal damage.
3.    C-reactive protein: deposits of this protein is found when calcium and group C polysaccharide (precursor of pneumococcus) meet. Works in non-adaptive immune response: increases phagocytosis response, C-reactive protein increases in acute infection. When there is FUO (fever of unknown origin), usually we check for C-reactive protein levels to see if it was caused by infection.
4.    B2-Microglobin: HLS – Histocompatibility antigen complex: regulates rejection response during tissue transplant. 

1. At the last amino acid, carboxylation of CF’s glutamate at gamma position (with help of γ-glutamyl carboxylase) forms γ-carboxyl-glumate. During this process, reduced cofactor Vitamin K is needed. 

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