Albumin and Other Plasma Proteins

I Pharmacokinetics. Valproate sodium is rapidly converted to valproic acid in the stomach, whereas divalproex sodium delayed-release and extended-release tablets must pass into the small intestine to be converted to valproic acid. Valproic acid is highly bound to albumin and other plasma proteins, and it is extensively metabolized in the liver. A summary of the absorption, distribution, metabolism, and elimination data for valproate is found in Table 68-11. ... 

Plasma P-lipoprotein concentration in rats receiving orotic acid falls to less than 1% of normal and rebounds to normal level within 48 hours following withdrawal of orotic acid [300]. When perfused in situ, the livers from orotic acid fed rats released a-lipoprotein, albumin, and other plasma proteins but no detectable p-lipoprotein. They also released smaller amounts of cholesterol and phospholipids than normal livers and no triglycerides, although they contained ten times the normal amount of triglycerides [300]. Since p-lipoprotein has a specific role in the normal transport of triglycerides, the fatty liver produced by orotic acid appears to result from the inhibition of synthesis or release of hepatic P-lipoprotein. 

Distribution naproxen has a volume of distribution of 0.16 L/kg. The elimination half-life of naproxen is approximately 15 hours following normal therapeutic doses. Naproxen is almost completely (99%) boimd to albumin and other plasma proteins. It crosses the placenta and appears in the milk of lactating women at approximately 1% of the plasma level concentration. Substantial amounts are found in the spinal fluid [1-3]. 

VII. Beversible Combination of Serum Albumin and Other Plasma Proteins... 

Vn. Reversible Combination of Sebum Albumin and Other Plasma Proteins with Small Molecules or Ions ... 

Displacement from albumin or other plasma proteins - most statins and fibrates are highly protein bound... 

Duan, X., D. Yarmush, F. Berthiaume, A. Jayaraman, and M. L. Yarmush. 2005. Immunodepletion of albumin for two-dimensional gel detection of new mouse acute-phase protein and other plasma proteins. Proteomics 5 3991 000. 

As discussed above, in retinol deficiency newly synthesized apo-RBP accumulates in the hepatic endoplasmic reticulum (microsomal fraction), whereas the secretion of serum albumin, TTR, and other plasma proteins appears to continue at a normal rate. The mechanisms responsible for the selective retention of RBP in the endoplasmic reticulum and for the specific stimulation of RBP secretion when retinol is made available, are not known. 

When most lipids circulate in the body, they do so in the form of lipoprotein complexes. Simple, unesterified fatty acids are merely bound to serum albumin and other proteins in blood plasma, but phospholipids, triacylglycerols, cholesterol, and cholesterol esters are all transported in the form of lipoproteins. At various sites in the body, lipoproteins interact with specific receptors and enzymes that transfer or modify their lipid cargoes. It is now customary to classify lipoproteins according to their densities (Table 25.1). The densities are... 

Mature human albumin consists of one polypeptide chain of 585 amino acids and contains 17 disulfide bonds. By the use of proteases, albumin can be subdivided into three domains, which have different functions. Albumin has an ellipsoidal shape, which means that it does not increase the viscosity of the plasma as much as an elongated molecule such as fibrinogen does. Because of its relatively low molecular mass (about 69 kDa) and high concentration, albumin is thought to be responsible for 75-80% of the osmotic pressure of human plasma. Electrophoretic smdies have shown that the plasma of certain humans lacks albumin. These subjects are said to exhibit analbuminemia. One cause of this condition is a mutation that affects spUcing. Subjects with analbuminemia show only moderate edema, despite the fact that albumin is the major determinant of plasma osmotic pressure. It is thought that the amounts of the other plasma proteins increase and compensate for the lack of albumin. 

Plasma proteins have been shown to be incorporated into normal bone matrix230,231,238. One plasma glycoprotein, identified in the human as the a2-HS-glycoprotein, is concentrated in bone and permanent dentine between 30—100 times in comparison with other plasma proteins. The a2-HS-glycoprotein is also concentrated in comparison with serum albumin in the mineral phase following either the... 

The extractability of I3IJ-labelled plasma albumin from bone pieces and from powdered bone has been compared after both in vivo and in vitro incorporation. Albumin is more readily extracted from bone pieces than from bone powder which implies that tissue disruption exposes additional protein adsorption sites. It has been suggested that incorporation of plasma albumin and other proteins into calcified matrix during bone formation occurs mainly as a result of its strong interaction with bone mineral237 239 240>. 

Several mechanisms have evolved to prevent this catastrophe. In bacteria and plants, the plasma membrane is surrounded by a nonexpandable cell wall of sufficient rigidity and strength to resist osmotic pressure and prevent osmotic lysis. Certain freshwater protists that live in a highly hypotonic medium have an organelle (contractile vacuole) that pumps water out of the cell. In multicellular animals, blood plasma and interstitial fluid (the extracellular fluid of tissues) are maintained at an osmolarity close to that of the cytosol. The high concentration of albumin and other proteins in blood plasma contributes to its osmolarity. Cells also actively pump out ions such as Na+ into the interstitial fluid to stay in osmotic balance with their surroundings. 

Over 50 mutant forms have been found and at least 30 persons have been found with no serum albumin in their blood.11 1 These analbuminemic individuals are healthy and have increased concentrations of other plasma proteins. 

Georgiou HM, Rice GE, Baker MS. Proteomic analysis of human plasma Failure of centrifugal ultrafiltration to remove albumin and other high molecular weight proteins. Proteomics 2001 1(12) 1503-1506. 

The specific interaction of Cibacron Blue and its derivatives to dinucleotides, mainly to NAD, NADP and ATP offers the possibility of purifing all enzymes which are dependent on these coenzymes. According to Mosbach < - > there are 163 enzymes requiring NAD, 141 enzymes requiring NADP, about 40 enzymes requiring NADP or NAD and 225 enzymes dependent on ATP. Besides these specific interactions non-specific interactions of Cibacron Blue and its derivatives with. proteins can also be applied for separation purposes. The non-specific interaction of Cibacron Blue with human serum albumin, for instance, enables albumin to be removed from transferrin, ceruloplasmin or other plasma proteins in order to purify human... 

Contrasting milieux. Cerebrospinal fluid has a low content of albumin and other proteins compared with plasma. 

About two-thirds of the zinc in pLasma is loosely bound to albumin. Most of the remaining zinc is tightly bound to other plasma proteins. A small fraction (2-37o) of plasma zinc is weakly bound to amino adds. The amino acids that most avidly bind zinc are histidine and cysteine. Amino add-associated zinc enters the glomerular filtrate and thus is a source of the zinc ions destined for excretion in the urine Most of the filtered zinc is reabsorbed and is prevented from immediate excretion. The zinc in red blood cells is bound to car nic anhydrase. Carbonic anhydrase is present at a level about 0,1% that of hemoglobin in the red blood cell on a poweight basis. The zinc content of mitochondria is about 1 nmol/mg protein (Unk and Jagow, 1995). 

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