Cystine deficiency

Data on atherosclerosis are very scarce. Mann and Stare (1954) reported the possibility of predisposing monkeys to atherosclerosis by giving a diet such as to cause a borderline cystine deficiency. Labecki et al. (1955) found an effect on the chylomicronemia in man, with a possible effect on the cholesterol level, on administration of a mixture of the lipotropic factors choline, methionine, and inositol (see Section II, 12). The methionine dose, however, was very much lower than those given to the toxemia groups. The problem is complicated further by the Weitzel (1956) report of a pro-atherosclerotic effect of methionine (1 %) as revealed by the fat content of the aorta in old hens. The serum cholesterol level decreased, however. Choline and inositol similarly did not give an improvement of the process in these animals (see also Section I, 12). 

Sulfur. Sulfur is present in every cell in the body, primarily in proteins containing the amino acids methionine, cystine, and cysteine. Inorganic sulfates and sulfides occur in small amounts relative to total body sulfur, but the compounds that contain them are important to metaboHsm (45,46). Sulfur intake is thought to be adequate if protein intake is adequate and sulfur deficiency has not been reported. Common food sources rich in sulfur are Hsted in Table 6. 

In terms of amino acids bacterial protein is similar to fish protein. The yeast s protein is almost identical to soya protein fungal protein is lower than yeast protein. In addition, SCP is deficient in amino acids with a sulphur bridge, such as cystine, cysteine and methionine. SCP as a food may require supplements of cysteine and methionine whereas they have high levels of lysine vitamins and other amino acids. The vitamins of microorganisms are primarily of the B type. Vitamin B12 occurs mostly hi bacteria, whereas algae are usually rich in vitamin A. The most common vitamins in SCP are thiamine, riboflavin, niacin, pyridoxine, pantothenic acid, choline, folic acid, inositol, biotin, B12 and P-aminobenzoic acid. Table 14.4 shows the essential amino acid analysis of SCP compared with several sources of protein. 

The grain or pulse forms of legumes have a high total protein content (20-26%) and can therefore be used as a natural supplement to cereals. Pulses are normally deficient in the essential amino acids methionine and cystine but contain enough lysine, whereas cereals are deficient in lysine but contain enough methionine and cystine. 

By the 1930s many workers had shown that nutritionally inadequate proteins, such as zein from maize, could be effective as a source of nitrogen if supplemented by additional amino acids (for zein, tryptophan). Even if it contained all the essential amino acids, the amount of protein in the diet influenced the results. Osbome and Mendel found that if the diet contained 18% by weight casein, which is low in cystine, young rats grew, but if the amount of protein was diminished, added cystine was required to offset the relative deficiency of this amino acid. Later, after methionine had been discovered, it was shown to replace the need for cystine. 

The biochemical defect is a deficiency or mutation of the gene that encodes the common membrane transporter for cystine and the dibasic amino acids. 

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. 

The AAA thus has two photometers in series. Since for every eluting amino acid both signals are recorded, the so-called 570/440 absorbance ratio may be of help in the identification process. As an example the simple primary amino acids have a 570/440 ratio of approximately 6, whereas the sulfur amino acids (cystine, sulfocysteine) have much lower ratios, approaching a value of 1. Small peptides and glycyl-amino acids will react with ninhydrin, an important fact for the diagnosis of prolidase deficiency and aspartylglycosaminuria. 

As a group, the caseins are deficient in sulphur amino acids which limits their biological value (80 egg albumen = 100). asl- and -caseins contain no cysteine or cystine while aa2- and x-caseins have two cysteine residues per mole, which normally exist as intermolecular disulphides. 

AAs methionine and cystine. Poor hatchability of fertile eggs can occur when diets of breeding hens are deficient in vitamin E. To prevent possible vitamin E deficiency, diets for growing poultry and breeding hens are usually supplemented with a source of vitamin E and possibly a suitable antioxidant. 

Nutritional Effects of Oxidized Sulfur Amino Acids. In 1937, Bennett (59, 60, 61, 62) already showed that the different oxidation products of methionine and cystine did not have the same biological effects to promote the growth of rats fed on diets deficient in sulfur-containing amino acids. Methionine sulfone and cysteic acid did not promote growth while the lower oxidation products had a positive effect and could replace methionine and cystine to a certain extent (see Table I). 

The metabolism of cystine and methionine. Availability of methionine in supplementing a diet deficient in cystine. Ibid., 98, 465 (1932). With R. W. Jackson. 

Animal experiments have shown that faulty nutrition, i.e. > 90% fat, < 10% protein and < 2 mg choline per day, leads to pronounced fatty fiver and even fatty cirrhosis within a few weeks. The same changes could be observed when the protein intake remained more or less normal, while extremely little methionine and choline was offered. With a partial surplus of certain foodstuffs, the special nature of the excessive nutritional components is also of considerable importance. The term partial malnutrition may, for example, be associated with a pronounced protein deficiency (and thus possibly inadequate production of lipoproteins) or a lack of lipotropic substances (such as methionine, choline, cystine, glycocoUbetaine, pyridoxine, casein and various N- or S-methylated substances). Protein deficiency has particularly severe consequences when toxic substances are absorbed at the same time or when the organism has to fight bacterial or parasitic infections. A diseased liver reacts to both a serious deficiency in and an excessive supply of different nutrients (e.g. proteins, certain kinds of amino acids, various lipids, trace elements) with unfavourable or even complicative developments during the course of disease. 

The nutritional requirements for a certain metabolite, however, may also be influenced by the cell population density. For example, serine, cystine, glutamine and asparagine have been shown to be required at low, but not at high, cell densities (Eagle Piez, 1962). This occurs in situations when the newly synthesized metabolite is lost into the medium in amounts that exceed the biosynthetic capacity of the cell. The critical population density can be regarded as that which is able to condition the medium, i.e. to build up a concentration in equilibrium with the minimum effective intracellular level, before the cells die of the specific deficiency. At high cell densities, however, the cell culture medium can require supplementation with extra amino acids, in order to prevent their depletion. 

Cysteine is oxidized to cystine, which may crystallize, forming kidney stones. In Hartnup s disease, the transport of neutral amino adds is defective in both intestinal cells and kidney tubules, resulting in deficiencies of essential amino acids. 

Wilson s disease or ceruloplasmin deficiency (autosomal recessive) Excess secretion of glycine, serine, and cystine Lenticular degeneration, positive copper balance, low serum ceruloplasmin levels, and defects in renal tubular reabsorption Mental retardation, ataxia, extrapyramidal symptoms, and cirrhosis Chromatography low blood and high urine copper levels low serum cemlc Iasmin (B8. H18. H19, PU. S9, W16)... 

Conservation of amino acids filtered at the glomerulus is made possible by the existence of four main transport systems for specific amino acids that facilitate active reabsorption of these amino acids from the proximal tubule. A lack or deficiency of the transport system responsible for the absorption of valine, alanine, cystine, and tryptophan, and of the transport system for arginine, lysine, cystine, and ornithine, leads to excretion of these specific amino acids in urine, which is characterized as renal aminoaciduria to distinguish it from overflow aminoaciduria. In the latter situation, the production of amino acids far exceeds the proximal tubular reabsorption capacity, thus leading to overflow of amino acids into urine. This can occur due to defective metabolism of amino acids, as is the case when phenylalanine cannot be metabolized due to the deficiency of the enzyme phenylalanine hydroxylase, or to the inability to deaminate amino acids in liver disease. 

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