Anion binding proteins

Delayed uptake of bilirubin has been described in mutant Southdown sheep (CIO), suggesting a deficiency in cytoplasmic organic anion-binding protein. Measurements of the conjugating enzymes are desirable. Conceivably, a decreased conjugating capacity could influence the uptake, as is suggested from studies on patients with Gilbert s syndrome (B14, B15,B18). 

Biological anion binding proteins and naturally occurring receptors such as the prodigiosins provide much of the inspiration for anion receptor chemistry. 

Most remarkably, one group of the bacterial binding proteins, which includes the two anion-binding proteins so far analyzed [specific for sulfate (115) and phosphate (116)], has even closer similarity. First, the polypeptide folding pattern in these proteins is almost identical to that in each lobe of lactoferrin (Fig. 15) the central /3-sheet of each... 

Medically, anions are of great importance in many disease pathways. Cystic fibrosis, a genetic illness affecting a significant proportion of society, is caused by misregulation of chloride channels (17). There is, therefore, a real need for selective halide detection, as established methods of chloride analysis are unsuitable for biological applications (18). Cancer is caused by the uncontrolled replication of polyanionic DNA. Anion-binding proteins have also been implicated in the mechanism of Alzheimer s disease (19). 

Figure 4.5 (a) the positions of the three amide NH atoms in the anion-binding nest motif found in a wide range of functional anion binding proteins, (b) the five-amide compound nest in the P-loop of p21 ras - a nucleotide triphosphate binding protein and (c) a six-amide compound nest surrounding the iron sulfur core in ferredoxin. (Reproduced from Section Key Reference with permission from Elsevier). 

F14. Fleischner, G., Robbins, J., and Arias, 1. M., Immunological studies of Y protein. A major cytoplasmic organic anion-binding protein in rat liver. J. Clin. Invest. 51, 677-684 (1972). 

Kaplowitz, N., Percy-Robb, I. W., and Javitt, N. B., Role of hepatic anion-binding protein in bromosulphthalein conjugation. J. Exp. Med. 138, 483-487 (1973). 

L6. Levi, A. J., Gatmaitan, Z., and Arias, 1. M., Deficiency of hepatic organic anion-binding protein, impaired organic uptake by liver and physiologic jaundice in newborn monkeys. N. Engl. J. Med. 283, 1136-1139 (1970). 

After the reduction of biliverdin, the bilirubin that is formed then undergoes a series of transport and transformation steps which ultimately lead to its excretion in the intestinal tract. From the sites of its production, bilirubin is released into the plasma where it efficiently binds to albumin, which acts as a plasma-transport system. The bilirubin-albumin complex is carried in the plasma to liver cells (hepatocytes), where the bilirubin is released from its albumin carrier protein and transported across the cell bilayer membrane into the hepatocyte. Once inside, the bilirubin is bound in the cytoplasm to anion-binding proteins such as ligandin. The latter carries the bilirubin to membrane-bound enzymes (localised in the endoplasmic reticulum of the liver cell) which catalyse the esterification of bilirubin, the ester groups (mainly p-D-glucuronoside, but also smaller amounts of fi-D-xylo-pyranosides and p-D-glucopyranosides) being transferred from their uridine diphosphate nucleotides. 

Figure 1 depicts the sequence of events associated with the cellular uptake of fatty acids and fatty acid oxidation. Fatty acid uptake by the cell takes place by mechanisms not completely understood. Fatty acid analogues such as bromo-palmitate have been reported to inhibit the intracellular accumulation of long-chain fatty acids (Mahadevan and Saver, 1971) suggesting that their transport may depend on specific transport systems. Once inside the cell, the fatty acids may be bound to anionic binding proteins such as described by Arias and others (Ockner t, 1972 ... 

The photosystems are the major elements of light-harvesting complexes (LHC, Section 9.5) in which the chlorophylls are bound to the membrane by two anionic binding proteins a major polypeptide may associate with both PS I and PS II and two distinct polypeptides may bind only one of the photosystems. Of the total number of chlorophyll molecules in a photosystem, a few are located in unique environments in which they trap absorbed energy and initiate photochemical activity. These traps are the reaction centres of PS I and PS II and are referred to as P7QQ and P g respectively because of their absorption maxima. P,jo contains either a single or an aggregation of two chlorophyll a molecules in association with a specific protein. Pgg is similarly a monomer or dimer of chlorophyll a but is associated with at least two proteins. 

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