Proteins in plasma

Protein S. Protein S is a single-chain molecule of approximately 78,000 daltons that contains 10 y-carboxy glutamic acid residues in the NH -terminal portion of the molecule. Protein S is a regulatory vitamin K-dependent protein. In plasma 40% of this protein circulates free and 60% circulates bound to C4b binding protein. Free Protein S functions as a nonenzymatic cofactor that promotes the binding of Protein C to membrane surfaces (22—25). 

The Concentration of Protein in Plasma Is Important in Determining the Distribution of Fluid Between Blood Tissues... 

F. The Levels of Certain Proteins in Plasma Increase During Acute Inflammatory States or Secondary TO Certain Types of Tissue Damage... 

Contrary to popular belief, ceruloplasmin5, the principal copper-containing protein in plasma, ceruloplasmin, is not involved in copper transport. This is clearly underlined by the clinical observation that patients with aceruloplasminaemia (i.e. lacking ceruloplasmin in their blood) have perfectly normal copper metabolism and homeostasis. Copper is transported in plasma mostly by serum albumin with smaller amounts bound to low-molecular weight ligands like histidine. Likewise zinc is mostly transported in plasma bound to proteins (albumin and ot2-macroglobulin). 

Haemoglobin, described in Section 5.3.1.3, is the most well known but it is just one of a number of carrier proteins present in blood. Albumin is quantitatively the most abundant protein in plasma. It is synthesized in the liver and circulates with a half life of about 3 weeks before being degraded or eliminated. Albumin has two very important functions to fulfil. First, it makes a significant contribution to the oncotic pressure of the blood and so influences the distribution of fluid between the intracellular and... 

Plasma binding - both the quantity and types of proteins in plasma differ in these classes of animals. Mammals tend to have large amounts of protein compared with fish (ca. 8 vs 3 g/100 ml) and albumin, the protein which binds most xenobiotics, is negligible in a number of fish species. 

Drug-protein binding is the reversible interaction of drugs v/ith different proteins in plasma. Albumin is not the exclusive protein involved. Drugs bind to specific sites on the protein. 

Ratio of binding proteins in extracellular fluid (except plasma) to binding proteins in plasma Correlation coefficient Elimination half-life Volume of distribution Volume of extracellular fluid Volume of plasma Volume of remaining fluid... 

Osserman, B. F., and Lawlor, D. P., Immuno electrophoretic characterisation of the serum and urinary proteins in plasma cell myeloma and Waldenstrom macroglobulinaemia. Ann. N.Y. Acad. Set. 94, 93-97 (1961). 

In the body retinol can also be made from the vitamin precursor carotene. Vegetables like carrots, broccoli, spinach and sweet potatoes are rich sources of carotene. Conversion to retinol can take place in the intestine after which retinyl esters are formed by esterifying retinol to long chain fats. These are then absorbed into chylomicrons. Some of the absorbed vitamin A is transported by chylomicrons to extra-hepatic tissues but most goes to the liver where the vitamin is stored as retinyl palmitate in stellate cells. Vitamin A is released from the liver coupled to the retinol-binding protein in plasma. 

Although it is primarily an intracellular compound, glutathione is secreted by epithelial and other cells. It may regulate the redox state of proteins in plasma and other extracellular fluids as well as within cells. In addition, glutathione released from the liver may be an important source of cysteine for other tissues. In the endoplasmic reticulum and the periplasm of bacteria glutathione functions in crosslinking thiol groups in newly formed proteins (Eq. 10-9). 

Less gas-liquid chromatographic interference occurs when protein in plasma and serum is precipitated with picric acid than with trichloroacetic acid or sulfosalicylic acid. Ultracentrifugation or membrane techniques could be used. The cation-exchange columns should be washed with water until no visible picric acid remains. 

Sirolimus is rapidly absorbed after it is given orally, and in healthy individuals, peak blood levels are achieved about an hour after oral administration. However, it takes twice as long to reach peak blood levels in kidney transplant patients. Its systemic availability is about 15% and high-fat meals interfere with the bioavailability. Sirolimus is bound (40%) to proteins in plasma, and its elimination half-life is about 12-15 h for transplant patients, but may vary. It is predominantly metabolized by CYP2A4 the drug has a number of active metabolites and is excreted in feces. 

Tamaoka A, Fukushima T, Sawamura N, et al. Amyloid beta protein in plasma from patients with sporadic Alzheimer s disease. J Neurol Sci 1996 141(l-2) 65-68. 

Anderson NL (2010) The clinical plasma proteome a survey of clinical assays for proteins in plasma and serum. Clin Chem 56 177-185... 

Addona TA, Abbatiello SE, Schilling B, Skates SJ, Mani DR, Bunk DM et al (2009) Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma. Nat Biotechnol 27 633-641... 

Keshishian H, Addona T, Burgess M, Kuhn E, Carr SA (2007) Quantitative, multiplexed assays for low abundance proteins in plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics 6 2212-2229... 

ApoSAA, normally a trace component of plasma, is an acute-phase plasma protein, that is, one that is elevated in a variety of disease states (R18). Its identification is interesting. A small protein of 76 residues, now called protein AA, was identified during the study of the proteins present in extracellular amyloid deposits in the type of amyloidosis particularly associated with inflammation (B24, H36, Lll, S38), Antibodies to protein AA reacted with two AA-related proteins in plasma, one of approximate Mr 180,000 (SAA) and the other found in HDL of Mr 14,000-15,000 or 12,000 (apoSAA) (A19, B25, B26, L12, L15). The N-terminal 76-amino-acid portion of apoSAA is identical to that of amyloid protein AA (E8). Human apoSAA has now been sequenced and has been shown to consist of 104 amino acid residues (B27). Further studies in man have demonstrated microheterogeneity in apoSAA (B18, B19, M30) and Benditt et al. describe specific amino acid substitutions (B27, P6). Shore et al. have described a second similar threonine-poor apolipoprotein, apparently a dimer of Mr 40,000... 

In intact cells insulin has been shown to stimulate receptor autophosphorylation. However, much smaller amounts of phosphotyrosine were found compared to that seen using purified, solubilized receptor preparations and, indeed, the predominant phosphorylation actually occurred on serine residues [69,71]. It has been suggested that there may be an insulin-stimulated, phosphoseryl-specific kinase which is loosely associated with the receptor and is activated by the receptor tyrosyl kinase [61]. This might account for the insulin-stimulated phosphoseryl kinase activity observed in both intact cells and when using crude, solubilized receptor preparations. Such an activity might also provide a mechanism for insulin s ability to enhance serine phosphorylation on target proteins in plasma membranes and elsewhere in the cell [25,78]. Nevertheless, (auto)-phosphorylation of the insulin receptor on tyrosine residues has been shown to occur immediately upon receptor occupancy by insulin and to precede any phosphorylation on serine residues [69]. Indeed, it remains to be seen as to whether the seryl phosphorylation occurs as a direct insulin-stimulation event or mediated by other kinases (cAMP/C-kinase) as a consequence of insulin-stimulated autophosphorylation on tyrosyl residues. 

D9. Dechaud, H., Lejeune, H., Garoscio-Cholet, M., Mallein, R., andPugeat, M., Radioimmunoassay of testosterone not bound to sex-steroid-binding protein in plasma. Clin Chem. 35, 1609-1614 (1989). 

Uranium is usually found in compounds which can be metabolized and recomplexed to form other compounds. In body fluids, tetravalent uranium is likely to oxidize to the hexavalent form followed by formation of uranyl ion. Uranium generally complexes with citrate, bicarbonates, or protein in plasma (Cooper et al. 1982 Bounce and Flagg 1949 Stevens et al. 1980). The stability of the carbonate complex depends on the pH of the solution, which will differ in different parts of the body (BEIRIV 1988). The low-molecular-weight bicarbonate complex can be filtered at the renal glomerulus, and be excreted in urine at levels dependent on the pH of the urine. The uranium bound to the protein (primarily transferrin) is less easily filtered and is more likely to remain in blood. In the blood, the uranyl ion binds to circulating transferrin, and to proteins and phospholipids in the proximal tubule (Wedeen 1992). 

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