Cystine in the urine

The cyanide nitroprusside test determines the presence of free sulfhydryl or disulfide compounds in urine samples [1, 3,4]. During the first step of the assay, cyanide reduces any disulfides that are present to free sulfhydryl compounds. In the second step, a reddish color reaction results when the free sulfhydryl groups complex with nitroprusside. A positive result is most usually due to cystine in the urine. Familial cystinuria is among the most common aminoacidurias. Disulfides are also excreted in other metabolic disorders such as homo cystinuria and ji-m e reap lol ac la le - cy s lei ne disulfiduria. Both will also produce positive results according to the following reaction RSH + Na2Fe(CN)5NO (sodium nitroprusside) — chromophore + NO. 

Free cysteine occurs only in very low amounts in the blood. Most of the potential free cysteine occurs as cystine where the two SH groups are oxidized to a disulfide bond. This compound can be reduced to cysteine where and when needed. Normally, the kidney reabsorbs both cysteine and cystine. In the disease cystinuria, the transport of cystine into many cells is defective. This causes an increase in plasma cystine, resulting in a spillage of cystine in the urine. Cystine is rather insoluble and forms stones in the kidney, bladder, and ureter, which can be extremely painful. Cystine has a lower solubility as pH decreases. 

The medication will help alkalinize the urine, which reduces the amount of cystine in the urine. ... 

Two human genetic diseases are known which involve this disulphide amino acid. In one, cystinuria , there is a transport defect in the intestine and kidney. This results in abnormally high levels of cystine in the urine and can result in the precipitation of cystine crystals and kidney stone formation. In cystinosis, cystine crystals form within cells and eventually cause severe kidney damage. The nature of the primary biochemical lesion is unknown all known cystine reduction systems of the cell appear to be normal. 

The answer is D. The patient s symptoms are consistent with a kidney stone, which is confirmed by the radiographic finding. The etiology of the stone is indicated by the urinalysis data, which suggest cystinuria. The cells of this patient s renal proximal tubules would be deficient in a transporter responsible for the reabsorptive uptake of cystine and the basic amino acids, arginine, lysine, and ornithine. Failure of the tubules to reabsorb these amino acids from the ultrafiltrate causes them to be excreted at high concentration in the urine. 

Cysteamine (/3-mercapto-ethylamine) is used for the treatment of nephropathic cystinosis. Cysteamine converts within lysosomes cystine into cysteine and cysteine-cysteamine mixed disulfide, both of which can exit the lysosome thus removing the extra cystine. After oral administration peak plasma levels are reached at about 1.4 hours post dose. It is eliminated as a sulfate in the urine with a half-life of 4-5 hours. The most frequent adverse reactions seen involve the gastrointestinal and central nervous systems. Side effects include abdominal pain, diarrhea, drowsiness, fever, loss of appetite, nausea or vomiting and skin rash. Confusion, dizziness and headache may occur. 

Excretion of cystine in abnormal amounts can occur in many other cases for instance in cystinosis, the characteristic feature of which is the deposit of cystine crystals in the body tissues, although cystinosis is not always accompanied by excessive excretion of cystine alone in the urine. In de Toni-Debre-Fanconi syndrome there is also an increased cystine output, but this is part of a generalized hyperamino aciduria such as... 

Dent et al. have tested the effect of ingestion of cystine, cysteine, or methionine on the blood level and mine output of cystine, using microbiological and polarographic methods their findings are considered to confirm the renal mechanism producing cystinuria. Only the administration of cysteine can raise the cystine level in the blood and its output in the urine, both in normal subjects and in cystinuric patients cystine clearances in the latter are 20-30 times more important than in the normal subject (D18, D19). 

A number of amino acid transport disorders may be associated with one or several of the systems described in Table 20.4. These are characterized by the excretion of amino acids in the urine but no increase in amino acid levels in the bloodstream. They are usually of hereditary origin. The most common disorder is cystinuria, characterized by the excretion of cystine. Because cystine is only slightly water soluble, cystinuria is often accompanied by the deposition of cystine-containing stones in the genitourinary tract. Cystinuria is apparently caused by a defect in the cationic amino acid transport system. Another disease that affects this system is lysinuric protein intolerance, which is associated with a failure to transport lysine, ornithine, arginine, and citrulline across membranes. Citrulline and ornithine are urea cycle intermediates (see later), and a disruption of their interorgan traffic results in hyperammonemia. 

There are two pyridoxal phosphate-requiring enzymes in the homocysteine degradation pathway, which are associated with genetic diseases. In homo-cystinuria, cystathionine synthase is defective, and large amounts of homocystine are excreted in the urine. Some homocystinurics respond to the administration of large doses of vitamin B6. In cystathioninuria, cystathionase is either defective or absent. These patients excrete cystathionine in the urine. Cystathionase is often underactive in the newborns with immature livers, and cysteine and cystine become essential amino acids. Human milk protein is especially rich in cysteine, presumably to prepare the newborn for such a contingency. 

E-7) Cystinuri. -This is a genetic disease affecting epithelial cell transport of cystine and certain other amino acids, resulting in cystine excess and cystine stones in the urine. 

Brand E, Harris MM, Biloon S. The excretion of a cystine complex which decomposes in the urine with the liberation of free cystine. J Biol Chem 1930 86 315-31. 

Several biomarkers of exposure have been identified for vanadium but none of them can be used to quantitatively determine exposure levels. Vanadium is found in the urine of exposed workers. This measurement is specific for vanadium. Some vanadium workers develop a characteristic green tongue, as a result of direct accumulation of the vanadium dusts on the tongue (Lewis 1959). One report from the 1950s states that vanadium exposure was associated with decreased cystine content in the fingernails of vanadium workers (Mountain 1955). However, alterations in cystine levels can also be associated with dietary changes and with other disease states, so this is not specific for vanadium exposure. No other commonly measured cellular changes have been identified with vanadium exposure. 

A variety of crystals may be present in the urine, including uric acid, calcium oxalate, calcium phosphate, calcium magnesium ammonium pyrophosphate, and cystine. Many of these have a unique crystalline form which permits them to be identified with microscopy. 

Awapara1623 observed an unknown 35S-cystine metabolite in the organs of rats. Cavallini and coworkers1626 have shown that this new metabolite is thiotaurine, NH2CH2CH2S02SH (197), which appears in the urine of rats fed a diet supplemented... 

Cal Kulis passed a renal stone shortly after admission, with immediate relief of flank pain. Stone analysis showed its major component to be cystine. Normally, amino acids are filtered by the renal glomerular capillaries into the tubular urine but are almost entirely reabsorbed from this fluid back into the blood via transport proteins in the proximal tubular cells of the kidney. Cal Kulis has cystinuria, a genetically inherited amino acid substitution in the transport protein that normally reabsorbs cystine, arginine, and lysine from the kidney lumen back into the renal tubular cells. Therefore, his urine contained high amounts of these amino acids. Cystine, which is less soluble than other amino acids, precipitates in the urine to form renal stones (calculi). 

In patients with cystinuria, such as Cal Kulis, the inability to normally absorb cystine and basic amino acids from the gut and the increased loss of these amino acids in the urine would be expected to cause a deficiency of these compounds in the blood. However, because three of these amino acids can be synthesized in the body (i.e., they are nonessential amino acids), their concentrations in the plasma remain normal, and clinical manifestations of a deficiency state do not develop. It is not clear why symptoms related to a lysine deficiency have not been observed. 

Cystinuria and cystinosis are disorders involving two different transport proteins for cystine, the disulfide formed from two molecules of cysteine. Cystinuria is caused by a defect in the transport protein that carries cystine, lysine, arginine, and ornithine into intestinal epithelial cells and that permits resorption of these amino acids by renal tubular cells. Cystine, which is not very soluble in the urine, forms renal calculi (stones). Cal Kulis, a patient with cystinuria, developed cystine stones (see Chapter 37). 

If the blood levels of methionine and homocysteine are very elevated and cystine is low, cystathionine p-synthase could be defective, but a cystathionase deficiency is also a possibility. With a deficiency of either of these enzymes, cysteine could not be synthesized, and levels of homocysteine would rise. Homocysteine would be converted to methionine by reactions that require B12 and tetrahydrofolate (see Chapter 40). In addition, it would be oxidized to homocystine, which would appear in the urine. The levels of cysteine (measured as its oxidation product cystine) would be low. A measurement of serum cystathionine levels would help to distinguish between a cystathionase or cystathionine p-synthase deficiency. 

Patients with this disorder often have urinary tract stones, which are caused by the limited solubility of cystine. A related disorder found in other people is characterized by the appearance of ornithine, lysine, and arginine in the urine, although the levels of urinary cystine are normal. 

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