Cystine excretion

Cystinuria. Penicillamine reduces excess cystine excretion in cystinuria. Penicillamine with conventional therapy decreases crystalluria and stone formation, and may decrease the size of or dissolving existing stones. This is achieved by disulfide interchange between penicillamine and cystine, resulting in a substance more soluble than cystine and readily excreted. 

A thorough investigation of this type of amino aciduria has led to a more accurate and more complete picture of it (S34). Taurine excretion is low proline, citrulline, and cystine excretion may be abnormally high, and when this is the case there does not seem to be a relation between the cystine output, which may be considerable, and that of lysine. Moreover, whereas the intake of a meal has but little influence on amino aciduria in normals, it has a definite effect on the output of amino acids in the case of Wilson s disease finally the amino acid fasting levels in plasma are at the lower limit of normal. 

Tiopronin, a thiol compound that stabilizes the cystine moiety, is used in prevention of urinary cystine stone formation in patients with severe homozygous cystinuria (urinary cystine excretion exceeding 500 mg daily) unresponsive to other therapies. 

Barnes, R. H., Kwong, E., and Fiala, G., 1965a, Effect of penicillin added to an unheated soybean diet on cystine excretion in feces of the rat, J. Nutr., 85 123-126. 

There are numerous abnormalities of cysteine metabolism. Cystine, lysine, arginine, and ornithine are excreted in cystine-lysinuria (cystinuria), a defect in renal reabsorption. Apart from cystine calculi, cystinuria is benign. The mixed disulfide of L-cysteine and L-homocysteine (Figure 30-9) excreted by cystinuric patients is more soluble than cystine and reduces formation of cystine calculi. Several metabolic defects result in vitamin Bg-responsive or -unresponsive ho-mocystinurias. Defective carrier-mediated transport of cystine results in cystinosis (cystine storage disease) with deposition of cystine crystals in tissues and early mortality from acute renal failure. Despite... 

The amounts of single amino acids excreted in urine in the conjugated form, as determined independently by Stein and Muting, are given in Tables 1 and 2. According to Stein, glycine, glutamic acid, aspartic acid, histidine, and proline are quantitatively the most important amino acids liberated in the course of urine hydrolysis. Serine, lysine, tyrosine, cysteine and cystine, threonine, alanine, valine, phenylalanine, and leucine are... 

The second and minor metabolic pathway consists of the reaction of cyanide with cystine to yield cysteine and B-thiocyanoalanine (Wood and Cooley 1955). The latter is then converted to 2-imino-4-thiazolidinecarboxylic acid and excreted in urine. Cystine has not been used for the purpose of mitigation of cyanide effects because its contribution to detoxification via this pathway is minor. 

The disease is characterized by excessive excretion of cystine and the dibasic amino acids arginine, lysine, and ornithine by the kidneys that may lead to precipitation of some of these compounds in the form of kidney stones. 

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. 

Mechanism of Action A heavy metal antagonist that chelates copper, iron, mercury, lead to form complexes, promoting excretion of copper. Combines with cystine-forming complex, thus reducing concentration of cystine to below levels for formation of cystine stones. Exact mechanism for rheumatoid arthritis is unknown. May decrease cell-mediated immune response. May inhibit collagen formation. Therapeutic Effect Promotes excretion of copper, prevents renal calculi, dissolves existing stones, acts as anti-inflammatory drug. 

Uric acid, cystine, and other weak acids are most easily reabsorbed from acidic urine. Therefore, renal excretion of cystine (in... 

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. 

Cysteine and cystine are relatively insoluble and are toxic in excess.450 Excretion is usually controlled carefully. However, in cystinuria, a disease recognized in the medical literature since 1810,451 there is a greatly increased excretion of cystine and also of the dibasic amino acids.451 452 As a consequence, stones of cystine develop in the kidneys and bladder. Patients may excrete more than 1 g of cystine in 24 h compared to a normal of 0.05 g, as well as excessive amounts of lysine, arginine, and ornithine. The defect can be fatal, but some persons with the condition remain healthy indefinitely. Cystinuria is one of several human diseases with altered membrane transport and faulty reabsorption of materials from kidney tubules or from the small intestine. Substances are taken up on one side of a cell (e.g., at the bottom of the cell in Fig. 1-6) and discharged into the bloodstream from the other side of the cell. In another rare hereditary condition, cystinosis, free cystine accumulates within lyso-somes.453... 

Uric acid, cystine, and some other weak acids are relatively insoluble in, and easily reabsorbed from, acidic urine. Renal excretion of these compounds can be enhanced by increasing urinary pH with carbonic anhydrase inhibitors. In the absence of continuous bicarbonate administration, these effects of acetazolamide are of relatively short duration (2-3 days). Prolonged therapy requires bicarbonate administration. 

Dubois et al. (D24) have made an intensive study of a case of de Toni-Debre-Fanconi syndrome in a 2-year-old child in which there were no cystine deposits they also found an abundant excretion of eitrulline, but no correlation between glycosuria and amino aciduria in the course of a glucose tolerance test (Fig. 4). 

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... 

Cystinuria has been known for a long time (A2, H18, Yl), but it was Dent and Rose (D12) who noticed, in 15 patients suffering from cystine caleulosis, that cystine was not the only amino acid abnormally abundantly excreted by the kidney. They observed that arginine and lysine were also excreted in abnormally large amounts, and Stein (S31) reported this to be true of ornithine as well. Bickel refers to the condition by using the expression lysine cystinuria, but this is in fact misleading because it infers that these are the only two amino acids concerned, whereas that is not the case. Taurine excretion, on the other hand, is low (S31). The cystine plasma level is either normal or low (D19, Fll). 

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. 

The clinical symptomatology, which is almost the same in all enzymatic disturbances of the urea cycle, is caused by hyperammonaemia. An arginase defect results in enhanced excretion of lysine, ornithine and cystine. Neurological symptoms such as hyperreactivity and athetosis followed by paresis and tetraplegia predominate. 

Ascorbic acid 4 g/day increases uric acid clearance in volunteers (23), although it does not reduce protein-bound uric acid in blood. Ascorbic acid 4-12 g/day causes acidification of the urine, which can cause precipitation of urate and cystine and consequently formation of urate stones or cystinuria. Ascorbic acid is excreted largely as oxalate, and hyperoxaluria results when large doses are... 

In 93 children with nephropathic cystinosis oral mercaptamine 51 mg/kg for up to 73 months produced 82% cystine depletion from leukocytes and improved creatinine clearance and growth (8). However, 14% of the patients could not tolerate the taste and smell of mercaptamine, which is excreted in the breath. 

Cystinuria is an autosomal recessive condition in which there is excessive urinary excretion of cystine because of a defect in proximal renal tubular reabsorption. In the most common form of the disease there is also excess excretion of the dibasic amino acids (lysine, ornithine, and arginine). These share the same renal tubular transporter although their presence in excess in urine appears benign. More rarely, isolated cystinuria is seen. The reader should note that cystinuria should not be confused with cystinosis, which is a condition associated with intracellular accumulation of cystine but not excess urinary excretion of cystine. 

The normal urinary excretion of cystine has been reported to be 4.81 to 48.1mg/24 hours (40 to 400p.mol/24 hours).Its relatively low limit of solubility, 18.0mg/dL (1500 LlmoI/L), is exceeded in many patients with cystin-uria, resulting in the formation of hexagonal crystals and, ultimately, cystine stones. Cystine stones are usually only seen in homozygotes, although there is some evidence that heterozygotes are at increased risk of stone formation. Cystinuria may present at any age from infancy to old age, although presentation is most common in the second and third decades. 

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