Circulating protein

Mutations in the antithrombin (AT) gene have been the basis of AT deficiency. In type I AT deficiency the level of circulating protein molecule and activity are reduced to nearly 50% of normal. Molecular defects in the AT gene resulting in gene deletions at specific DNA sequences may be the basis for type I AT deficiency predisposing such patients to thrombosis (82). 

Pharmaceutical drug development of small molecules is initially based on the selection of candidate targets - mainly enzymes, receptors or circulating proteins that are currently targeted by 45, 28 and 11% of marketed compounds, respec-... 

While the majority of attention has focused on peptides contained within the nervous system, two other important methods for delivering peptides to the vicinity of the mast cell have been established (1) peptides produced and secreted by other cells of inflammation that may affect mast-cell function and (2) the local generation of mast-cell-active peptides by secreted enzymes acting on circulating protein precursors. Examples of the former include several, as yet ill-defined, peptide factors and cationic proteins from other immunocompetent cells [66-69], defined lymphokines such as the interleukin-1 [70] and interleukin-3 [71], and tumour necrosis factor [70], Examples of the latter include bradykinin [72] and a recently identified peptide produced by the action of acid proteinases on albumin [73, 74]. 

In severe malnutrition where circulating protein concentrations are very low, in uraemia and in pregnancy, the distribution of the drug (e.g., anticonvulsants) between bound and free forms may alter, and when monitoring treatment it may be necessary to get the laboratory to measure free concentrations of the drug. However this can only be done in specialised centres, even in developed countries, and is not usually available elsewhere. 

Some proteins are imported into cells from the surrounding medium examples in eukaryotes include low-density lipoprotein (LDL), the iron-carrying protein transferrin, peptide hormones, and circulating proteins destined for degradation. The proteins bind to receptors in invaginations of the membrane called coated pits, which concentrate endocytic receptors in preference to other cell-surface proteins. The pits are coated on their cytosolic side with a lattice of the protein clathrin, which forms closed polyhedral structures (Fig. 27-40). The clathrin lattice grows as more recep-... 

A major application of monoclonal antibodies is in clinical assays for drugs, bacterial and viral products, tumor antigens, hormones, and other circulating proteins. Their use in conjunction with immunoassays (Box 31-C) has provided increased specificity and sensitivity. Another major application is to observe binding of antibodies to specific proteins by electron microscopy. The location of specific receptor proteins can be established - as can the locations of ribosomal proteins and many other cellular components (Fig. 29-1). Monoclonal antibodies to acetylcholine receptors have been shown to induce symptoms of myasthenia gravis (Box 31-D), supporting the autoimmune origin of that disease. 1 Monoclonal antibodies specific for such a small hapten as mercuric ion have been isolated.k... 

Angiotensinogen is the circulating protein substrate from which renin cleaves angiotensin I. It is synthesized in the liver. Human angiotensinogen is a glycoprotein with a molecular weight of approximately 57,000. The 14 amino acids at the amino terminal of the molecule are shown in... 

Metallothionein is a metal storage protein, not a circulating protein. Superoxide dismutases are present in various subcellular particles, for example mitochondria. Peroxisomes contain peroxidases such as catalase. Superoxide dismutases convert the superoxide anion to H202 and are absent from anaerobic microorganisms. 

When vitamin A stores are adequate, the liver secretes retinol bound to retinol-binding protein (RBP) into the circulation to provide tissues with a constant supply of vitamin A. In the circulation, the retinol-RBP complex is found bound to another circulating protein of hepatic origin, transthyretin (TTR). TTR also binds thyroid hormone and consequently plays a role in the transport of both vitamin A and thyroid hormone. The molecular size of the retinol-RBP complex is quite small, and the formation of the... 

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