Methionine cystine synthesis

Growing chicken128 and hens129 utilize sulphate sulphur for cystine synthesis. Biological radio-tracer experiments130 with Na235S04 (10 fiCi) have shown that over 65% of the 35S administered to a 24-hour-old embryo is incorporated into taurine of the chick. No radioactive cystine, methionine or cysteic acid was detected in the hydrolysate obtained from the embryo and only a small portion of total taurine-35S occurs as taurocholic acid. The embryo is unable to utilize sulphate sulphur for cystine synthesis. 

FUNCTIONS OF SULFUR. Sulfur has an important relationship with protein. It is a necessary component of the sulfur-containing amino acids methionine, cystine, and cysteine. Sulfur is present in keratin, the tough protein substance in the skin, nails, and hair and it appears to be necessary for the synthesis of collagen. 

Maintenance can be defined as the state in which the intake of nitrogen is exactly equal to the sum of the losses, to keep the body nitrogen content constant (Owens and Pettigrew, 1989). Methionine+cystine (M C) are essential for body maintenance, as part of metabohc processes and also for cell synthesis and renewal (Baker, 1991). This study aimed to estimate the digestible M C requirement for maintenance using adult roosters of different body weights and composition. 

A newer therapeutic approach is the administration of betaine (6-12 g daily), which lowers homocysteine levels by favoring remethylation [33], A theoretical hazard of betaine treatment is increasing the blood methionine, sometimes to an extravagant degree ( 1 mmol/1). Experience to date indicates that betaine administration is safe, with no major side effects except for a fishy odor to the urine. Other therapeutic approaches have included the administration of salicylate to ameliorate the thromboembolic diathesis. Patients also have been treated with dietary supplements of L-cystine, since the block of the transsulfura-tion pathway in theory could diminish the synthesis of this amino acid. 

Catalytic hydrogenation of peptides containing a Phe(4-N02) residue, to be subsequently converted into Phe(4-N3), that also contain cystine and/or methionine residues, requires extended reaction times. This may lead to desulfuration. Therefore, a Phe(4-NH2) residue is used as a precursor for Phe(4-N3) in the synthesis of AVP to give Phe(4-N3) residues at either position 2 or 3.1281 In this solution-phase synthesis, the 4-amino group in the 4-amino-... 

It was confirmed later that free cysteic acid and free methionine sulfone were not biologically available (63, 64,138) and that free methionine sulfoxide was partly available. Miller and Samuel (64) observed that the food efficiency of a mixture of free amino acids was lower when the methionine source was replaced by methionine sulfoxide. The food efficiency was restored when 50% of the methionine sulfoxide was replaced by free methionine. Gjoen and Njaa (66) confirmed that free methionine sulfoxide was nearly as available as methionine when the amino acid mixture contained cystine. This suggests that methionine sulfoxide is reduced before it is used for protein synthesis. In order to elucidate this point, we have compared the metabolic transit of free methionine sulfoxide with that of free methionine. 

Synthesis of sulfur amino acids from inorganic sulfate by ruminants. II. Synthesis of cystine and methionine from sodium sulfate by the goat and by the microorganisms of the rumen of the ewe. Arch. Biochem. Biophys., 33, 353... 

By contrast, the amino acid compositions of the two forms of inver-tase (internal and external) differ significantly in the number of residues of certain amino acids. These differences occur notably in the content of serine, alanine, cystine, methionine, tyrosine, lysine, and histidine. The significance of these differences is not yet apparent, but these two invertases are obviously not isoglycoenzymes. The synthesis of proteins having such diverse amino acid compositions as have the two invertases would probably necessitate two separate genetic-control mechanisms. 

Independently whether partial oxidation of Met residues occurs during the synthesis or whether Met(O) derivatives are purposely used, the sulfoxide has to be quantitatively reduced in the final steps to regenerate the methionine peptides. For this purpose, various reagents were proposed for the reduction in aqueous solution upon final deprotection and in organic solvents generally prior to the deprotection step in the presence or absence of cystine disulfides. 

Methionine produces cystine and taurine breaks down fats reduces blood cholesterol detoxifies the liver is an antioxidant and protects hair, skin, and nails. It is needed for synthesis of RNA and DNA and it assists in the breakdown of niacin, histamine, and adrenalin. It binds to heavy metals, such as lead and cadmium, and carries them out of the body. 

The availability of L-cysteine is the rate-hmiting factor for GSH synthesis under physiological conditions. Cysteine derives from the diet, from proteolysis or alternatively is synthesised from methionine via the transulphuration pathway [36] (Fig. 2). The fact that fasting induces a fall of GSH levels to 50% of the controls highlights the importance of the nutritional status on GSH synthesis. Indeed, fasting for 48 h causes a marked glutathione depletion in the Uver and GSH levels are restored upon refeeding [37]. Moreover,hepatic GSH levels are particularly related to the cysteine and/or cystine content of the diet. 

Chick embryo utilizes 35S-sulphate for the synthesis of 35S-taurine, but the amount of sulphate-sulphur present in the unincubated egg is insufficient to furnish S necessary for the taurine synthesized. Injection167 of L-methionine-35S or of L-cysteine HCl-35S into the egg white, and determination of the distribution of 35S in the chick hatched from the incubated egg revealed that with [35S]cysteine 10% of the administered 35S is located in the chick as taurine, 12% as sulphate, 1.3% as methionine and 49% as cystine. With methionine-35S 9.1% was recovered as taurine, 10% as sulphate, 43% as cystine and 35% as methionine. These findings indicate that methionine is converted to cystine during embryonic development, but significant amounts of cysteine-35S were incorporated also into methionine. Possibly, trans-sulphonation from methionine to cysteine is reversible to some extent in the chick embryo, similarly to what has been found in young rats168. 

The defect in mucopolysaccharide synthesis together with the increased incorporation of methionine sulfur and the decreased cystine content may reflect an increased epithelial cell turnover, as suggested by the hyperplastic mucosa and the masses of epithelial cells in the biliary tract, but the picture is not yet complete. In any case, it is clear that desquamated cells appear to be the most important factor in this form of cholelithiasis. The contribution of cellular debris to other types of gallstone formation has been discussed in previous sections. 

On the basis of theoretical considerations, it had been su ested that the beta cell may have a low GSH content (44). The synthesis of insulin by the beta cell appears to be dependent upon a continuous supply of sulfur-amino acids, for when rabbits are placed on a cystine-methionine-deficient diet the insulin content of the pancreas is decreased (32). Insulin, in contrast to most other proteins, contains 12 % cystine (45). Since cysteine or its oxidized derivative, cystine, is a constituent of both GSH and of insulin, there may well be competition for this amino acid within the beta cell. Thus the GSH concentration within the beta cell may be low as a consequence of insulin synthesis (44). Furthermore, the oxidation-reduction potential in the beta cell may favor the oxidation of GSH to its oxidized form (GSSG) (44). Both of these factors would increase the susceptibility of the beta cells to alloxan, for it is the reduced form of GSH which reacts with alloxan (26). 

Fatty livers are also formed, in the presence of adequate choline, by diets deficient in amino acids other than methionine. This has been shown for threonine (SiNGAL et al. 1954) lysine and tryptophan (Vennart et al. 1958). Threonine deficiency, like choline deficiency, also leads to an increased synthesis of fatty acid from acetate (Yoshida and Harper 1960). An increase in synthesis has also been observed when cystine is added to a low protein diet. The relative importance of these effects for the formation of fatty livers is still uncertain. 

The introduction of radiosulfur into proteins after methionine feeding indicates a synthesis of peptide bonds. That the opening and reclosing of peptide bonds is a rapid process is shown by numerous investigations by Schoenheimer and co-workers (160), and the above results of Tarver and Schmidt (172) can be interpreted as a further proof of the rapid turnover of tissue proteins. Du Vigneaud and associates (179) applied the stable sulfur isotope as a tracer. When administering labeled methionine to rats kept on a diet free of cystine, up to 80% of the derived cystine produced in the rats was found to contain sulfur from methionine. 

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