Role of Serum Proteins

Sawada and coworkers [25-27] studied the iso-pH 7.4 MDCK permeabilities of very lipophilic molecules, including chlorpromazine (CPZ) [25], These authors included 3% wt/vol bovine serum albumin (BSA) on the apical (donor) side, and 0.1-3% BSA on the basolateral (acceptor) side, and found that plasma protein binding greatly affected the ability of molecules to permeate cellular barriers. They observed cell tissue retention of CPZ ranging from 65 to 85%, depending on the 

Yamashita et al. [33] also studied the effect of BSA on transport properties in Caco-2 assays. These authors observed that the permeability of highly lipophilic molecules could be rate-limited by the process of desorption from the cell surface into the receiving solution, due to high membrane retention and very low water solubility. They recommended using serum proteins in the acceptor compartment when lipophilic molecules were being assayed - a common circumstance in discovery settings. 

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Figge J, Rossing TH, Fend V. The role of serum proteins in acid-base equilibria. J Lab Clin Med 1991 117 453-67. 

The free fatty acid uptake by tissues is related directly to the plasma free fatty acid concentration, which in turn is determined by the rate of lipolysis in adipose tissue. After dissociation of the fatty acid-albumin complex at the plasma membrane, fatty acids bind to a membrane tty acid transport protein that acts as a transmembrane cotransporter with Na. On entering the cytosol, free fatty acids are bound by intracellular fatty acid-binding proteins. The role of these proteins in intracellular transport is thought to be similar to that of serum albumin in extracellular transport of long-chain fatty acids. 

The role of A3 adenosine receptors in modulating inflammatory responses was also confirmed in mice after its targeted deletion. Adenosine mediates an increase in cutaneous vascular permeability leading to extravasation of serum proteins as an important mechanism in the development of an inflammatory response. It turned out that this reaction is dependent on the presence of A3 adenosine receptors on mast cells as both A3 knockout mice and mice lacking mast cells showed no response (Tilley et al. 2000). Adenosine accomplishes mainly an anti-inflammatory effect which is generally assumed to be mediated by the A2A subtype (Sitkovsky et al. 2004). However, A3 agonists were also found to produce anti-inflammatory actions, for example by inhibiting neutrophil function. Such a contribution to inhibition of inflammation was recently confirmed in a comparison of A2A and A3 knockout mice (van der Hoeven et al. 2008). 

Schade reviewed (114) the earlier studies on the role of serum transferrin in iron transport. Various early investigators had observed that the blood serum transferrin rapidly bound iron administered either through the gastrointestinal tract or by intravenous injection. There was a rapid turnover of iron in the blood serum and the degree of saturation of the transferrin was related to the amount of iron administered. In no instances, however, was the blood serum transferrin ever saturated with iron. Jandl et al. (71) have shown that both ovotransferrin and serum transferrin can transport plasma iron into red cells and that the transport is dependent on the concentration of transferrin. Iron taken up by the blood cells could not be eluted by subsequent incubation with iron-free transferrin solutions. More recently Morgan and Laurel (99) reported that iron uptake in reticulocytes is independent of the transferrin concentration. The iron complex of serum transferrin has a higher affinity for immature red cells than does the iron-free protein (72). Both bind specifically to immature red cells and the attachment permits the cells to remove the iron. Once the iron is removed, however, the iron-free transferrin can be replaced by an iron-transferrin complex. 

Thus with the re-emergence of the dominant role of the amino acids, envisioned by Vickery, Block returned to the theater and began to replay his part in the investigation of serum proteins of a quarter of a century ago, only to be cut off as a result of an untimely accident. 

Baxter RC. Insulin-like growth factor (IGF) binding proteins The role of serum IGFBPs in regulating IGF availability. Acta Paediatr Scand Suppl 1991 372 107-14. 

De Haas CJ. New insights into the role of serum amyloid P component, a novel lipopolysaccharide-binding protein. FEMS Immunol Med Microbiol 1999 26 197-202. 

Tryptophan and tryptophan pyrrolase in heme regulation. The role of lipolysis and direct displacement of serum protein-bound tryptophan in the opposite effects of administration of endotoxin,... 

R. Ekins, Role of serum thyroxine-binding proteins and maternal thyroid hormones in... 

Ekins, R. P. Hypothesis The roles of serum thyroxine binding proteins and maternal thyroid hormones in foetal development. Lancet (i) 1129-1132, 1985... 

The biosynthesis and regeneration of these photosensitive pigments requires that retinaldehyde (or a retinoid precursor) is provided to the membranes in which they are sequestered. The delivery of retinoids to these membranes, which are generally found in specialized photoreceptor cells, has been investigated in some vertebrates. In these animals, proteins called retinoid-binding proteins serve as vehicles that transport retinoids in the serum, cell sap, and interstitial space of the eye. The critical role of these proteins in the normal functioning of the vertebrate visual system is one of the major topics of this chapter. 

A likely difference in the metabolism of free and chelated sources lies in post-absorptive processes, particularly transport in the bloodstream. The study of the interactions of insulin-enhancing compounds with serum proteins has been almost exclusively studied by EPR. Apo-transferrin and albumin have been implicated in the transport of vanadyl ions in the blood, and these proteins represent a significant metal-binding capability in the blood. Considerable interest in the role of these proteins in the transport and biotransformation of administered vanadium compounds has been evident in the recent literature. 

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