Urine, mucoproteins

Mechanism of Action An intratracheal respiratory inhalant that splits the linkage of mucoproteins, reducingtheviscosityof pulmonary secretions.Tiierapeutic Effect Facilitates the removal of pulmonary secretions by coughing, postural drainage, mechanical means. Protects against acetaminophen overdose-induced hepatotoxicity. Pharmacokinetics Protein binding 83% (injection). Rapidly and extensively metabolized in liver. Deacetylated by the liver to cysteine and subsequently metabolized. Excreted in urine. Half-life 5.6 hr (injection). 

Of the three naturally occurring hexuronic acids, D-glucuronic acid appears to be by far the most widely distributed. It has not been found free in Nature, except possibly in small amounts in blood and urine, but it occurs in a wide variety of polysaccharides and mucoproteins of plant, animal and bacterial origin, and plays an important part in the metabolism of many types of organic compounds. 

Grassmann and Schleich have shown by Sorensen s method that ox-skin collagen contains equimolecular amounts of D-glucosamine and D-galactose, and a complex with the same proportions of these constituents has been reported in the protein of the ovalbumic glands of Rana esculenta. The mucoproteins of urine are as yet unexplored except insofar as they are known to contain small amounts of certain of the blood group factors. ... 

These are generally made up of metabolic products present in the glomerular filtrate at levels close to their maximum solubility limit. Variation of the pH and composition of the urine or obstruction to urine flow may result in precipitation of substances in the kidney and contribute to calculi formation. Urinary calculi may be composed of calcium-containing stones such as calcium oxalate or calcium phosphate, both with and without magnesium ammonium phosphate, and stones containing either cystine, xanthine, or uric acid (21). The mucoprotein core around which the mineral salts precipitate account for 60% of the composition of the stone. 

Another controversy surrounds the amount of glycoprotein (mucoprotein) excreted in the urine of adults with and without stones. Some reports showed that there is no difference in the excretion of uromucoids (B2, SI, S2), whereas others found that the excretion of uromucoid-rich material in calcium stone patients was greater than in their healthy counterparts (B3, K2, M5). This controversy may be attributed to different methods of urine storage, because it has been reported that the physical properties of the mucoproteins are altered by freezing (B3). Nevertheless, urine of black persons, who seldom develop stones, contains no uromu-coid (Kl, Ml). 

B3. Boyce, W. H., and Swanson, M., Biocolloids of urine in health and in calculous disease. II. Electrophoretic and biochemical studies of a mucoprotein insoluble in molar sodium chloride. J. Clin. Invest. 34, 1581-1589 (1955). 

R4. Rose, G. A., and Sulaiman, S., Tamm-Horsfall mucoprotein promotes calcium phosphate crystal formation in whole urine Quantitative studies. Urol. Res. 12, 217-221 (1984). 

Tl. Tamm, I., Horsfall, F. L., A mucoprotein derived from human urine which reacts with influenza, mumps, and Newcastle disease viruses. J. Exp. Med. 95, 71-97 (1952). 

B8a. Bjornesjo, K. B., Werner, I., and Odin, L., The influence of surgeiy on serum and urine hexosaiuine, serum mucoprotein, glutamic-oxaloacetic transaminase (GOT) and C-reactive protein. Scand. J. Clin. Lab. Invest. 11, 238-244 (1959). 

In contrast to serum, urine can fluctuate dramatically in protein and salt concentrations, and both the inter- and intra-patient variability can be quite large. Typically, the urine samples containing the highest protein concentrations are first and second morning void samples. To minimize the impact of this variability in the clinical setting, samples are often collected over the course of 24 h (8). Urine from normal individuals has low protein concentrations (150 mg/day). Approximately 10% of this protein is albumin the remaining proteins are various serum proteins as well some that arise from the renal cells themselves (9). Fifty percent of the protein is the Tamm-Horsfall mucoprotein (96 kDa), which is secreted by cells of the ascending limb of the loop of Henle (10). 

Summerizing it can be said that a higher percentage of the patients with uric acid stones have an increased P2 -microglobulin excretion than patients suffering from oxalate stones. Furthermore our study shows that in this group of patients Uromucoid, GAG, and Citrate excretion are decreased. We think that our findings must be interpreted in the way that tubular defects in patients with uric acid stones are not rare. It seems that the acidification, reabsorption, and the decrease of the acid mucoprotein in the urine support this hypothesis. 

In spite of these difficulties, several major observations have already been made. In humans, erythropoietin is found only in the urine of anemic patients. The partially purified hormone is likely to be mucoprotein strangely enough, erythropoietin does not exhibit any species specificity, and the human hormone stimulates erythropoiesis in the monkey and the guinea pig [21-25]. 

A substance with similar immunological properties has been found in the kidney, where it is more abundant in the cortex than in the medulla. According to Boyce and King [90, 91], the mucoprotein is consistently found in the kidneys of patients with recently formed stones, but is rarely present in patients with other kidney diseases in which stones are not formed (e.g., renal carcinoma and severe renal arteriosclerosis). The mucoprotein has not been detected in normal kidneys or in patients with pyelonephritis, and the compound cannot be immunologically detected in blood serum, human saliva, or bone matrix. The only other tissue where this matrix substance has been detected is the intestine. (Boyce and King think that this is not a coincidence and that the reason for its presence in kidney and intestine is that both these organs are involved in calcium absorption.) But most important to the pathogenesis of lithiasis are the mucopolysaccharides found in urine. 

Human and animal urine contains variable amounts of low molecular weight, alcohol-soluble proteins that contain carbohydrates (up to 40%). Changes in the mucoprotein composition of urine could precipitate stone formation as a result of either qualitative or quantitative alterations. Therefore, it is significant that the concentration of total nondialyzable urinary mucoproteins is considerably increased in calculus disease (5 times). 

A similar threadlike protein has been found in bovine urine. It is approximately 150 A wide, the beading occurs every 200 A, and it may be 25,000-40,000 A long. The bovine urinary protein contains 4% sialic acid, 6% hexose, and 5% hexosamine. It is not known if glycoproteins with similar properties are responsible for the PAS-positive reaction observed in the renal tubules of sheep receiving an experimental diet. The use of fluorescent antibodies could help in answering that question. The role of the mucoproteins in forming stone matrices is unknown. 

Experimental urolithiasis is produced in beef by feeding them a diet supplemented with K2HPO4. PAS stains demonstrate that glycoproteins accumulate in the cells of the proximal and distal convoluted and collecting tubules. The proximal convoluted tubules seem to be more affected than the other segments of the nephron. PAS-positive casts are also found in the urine. Moreover, examination of the urine by ultrafiltration, electrophoresis, and chromatography on DEAE-cellulose columns demonstrated the presence of a mucoprotein similar to that found in human stones. 

A renally derived mucoprotein which is normally excreted in small amounts (4 mg/day) in the urine. 

The chromatographic techniques has been useful for investigations of carbohydrates of animal origin, such as those in human cerebrospinal fluid (90,91), foetal and maternal blood of sheep (202), urines (26,90,134), the polysaccharide components of sea urchin eggs (241), capsular polysaccharides (95), blood group polysaccharides (6,7,10), semm and urinary mucoproteins (94), cornea polysaccharides (258), frog spawn mucin (101), and hyaluronic acid (161). 

Appearance.— Fresh urine is usually transparent, but may be opaque after meals owing to the alkaline tide causing a precipitation of calcium and magnesium phosphate (p. 395). As urine cools, a cloudy suspension of mucoprotein from the urinary tract may appear in the body of the fluid. 

Cornelius, C. E., Pangbom, J., and Heckly, R. J., 1%3, Isolation and characterization of a urinary mucoprotein from ovine urine. Arch, Biochem. Biophys. 101 403. 

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