Methionine deficiency

Miller, R. A., Buehner, G., Chang, Y., Harper, J. M., Sigler, R., and Smith-Wheelock, M. (2005). Methionine-deficient diet extends mouse lifespan, slow immune and lens aging, alters glucoase, T4, IGF-1 and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell 4, 119-125. 

Conversely, he observed that vitamin B 2 may serve to enhance the carcinogenic effect of p-dimethylaminoazobenzene in rats fed a methionine-deficient diet. It is important to note, however, that this was only true in rats on a methionine-deficient diet. 

Microsomes from rats fed diets deficient in methionine and containing added methionine have the lowest levels of cytochrome P-450, the modified AIN-76 (methionine deficient) diet apparently causing a depression in the level of cytochrome P-450 compared to the control (AIN/MET) diet (Table I). The other diets induced cytochrome P-450 in the livers, including the chow diet which induced cytochrome P-450 approximately twice as much as any of the other diets. In addition, chow and AIN/CSA shifted the... 

Methionine is intimately related to lipid metabolism in the liver. Methionine deficiency is one of the causes of the fatty liver syndrome. Lack of methionine prevents the methylation of phosphatidylethanolamine to phosphatidylcholine, resulting in an ability by the liver to build and export very low density lipoprotein. The syndrome can be treated by the administration of choline, and for this reason, choline has often been referred to as the lipotropic factor. 

Salbe, A. D., and Lovander, O. A. (1990). Comparative toxicitj and tissue retention of selenium in methionine-deficient rats fed sodium selenate or i.-selenomethi nine. /-Nutr. 120,207-212. 

Phenylmethylsulfonyl fluoride prevents delayed neurotoxicity from OPs if administered before exposure but potentiates neurotoxicity if administered after exposure (Pope and Padilla 1990). Alcohol and drug abuse also potentiate insecticide toxicity, but symptoms are not specific (Calabrese 1978). Protein-deficient diets increase susceptibility to OP poisoning (Boyd and Chen 1968 Krijnen and Boyd 1971). Special diets increase risks for infants, food faddists, and individuals with protein deficiency, including persons in developing countries with protein-deficient diets. Individuals with vitamin A, vitamin C, or methionine deficiencies may be susceptible to CH insecticides (Calabrese 1978). The environmental temperature and fat solubility of OPs have marked effects on their toxicities (J. E. Davies et al. 1975 Wheeler 1987). 

The results show that the incidence of heart lesions in male rats is not altered by increasing the level of protein from 20 to 25% (Beare-Rogers et a., 1974), or by substituting different quality proteins, i.e., casein vs. a casein-soybean meal mixture (Vies etai, 1976). Some recent publications suggest that the methionine content in the rat diets may be deficient if casein is fed as the only source of protein and that methionine deficiency increases the incidence of heart lesions (Clandinin and Yamashiro, 1980, 1982). Different results were obtained by Farnworth et al. (1982c), who found that the addition of methionine to casein-containing diets improved the growth of rats but that the incidence of heart lesions was not affected. 

For the identification of the EMC proteins in HeLa cells, Butterworth t used pulse-chase experiments done at a time of infection when host protein synthesis is blocked, and only the viral proteins are being formed. The stable EMC proteins were identified after 1 h chase with cold amino acids. In an attempt to obtain a purified EMC replicase containing an assumed EMC stable protein we carried out a similar experiment. A suspension of 1.5 X 1q9 infected BHK cells was maintained for 4 h in a methionine-deficient medium, containing actinomycin I) (10 ng/ml). 

Methionine deficiency leads to coproporphyrin accumulation. Lascelles and Hatch [145] suggested that heme formation may be inhibited under these conditions, perhaps at the iron insertion step because methionine is required for the synthesis of phosphatidyl choline and the latter appears to be needed for ferrochelatase activity. Tait [147a] reported that under anaerobic conditions the conversion of coproporphyrinogen to protoporphyrinogen required methionine, ATP, and ferrous ions. 

The controls of the heme-BCHL biosynthetic chain are summarized in Fig. 10. As discussed above, at least three kinds of control regulate ALA-synthetase activity. One is by heme acting as corepressor in the synthesis of this enzyme (2). Another is by heme acting as inhibitor of the enzyme (3). A third is by activation possibly of a precursor ALA-synthetase, the ratio of activator to inhibitor serving to control the degree of activation (1). Another control is somewhere between coproporphyrinogen and heme as revealed in methionine deficiency (4). In addition there is a control of the enzymes of the Mg branch (5), in contrast to those enzymes from ALA to heme. The enzymes of the Mg... 

Yet, studies in bacteria continue to yield intriguing results when E. coli are grown in a methionine-deficient medium, tRNA is synthesized but not methylated. Such tRNA usually binds to codon enzymes and ribosomes normally. However, there are exceptions and further studies are needed to evaluate the role of methylation in tRNA function. 

For pulse-labeUing, add 0.5 mQ p S]methionine in 2 ml methionine-deficient growth medium and incubate the dish of cells at 37 °C (or appropriate temperature) for up to 2 h. For very short pulses (e.g. 5 min), pre-incubate the cells in methionine-deficient medium for 30 min to reduce the cellular pools of methionine. 

Other investigators have reported a decreased blood GSH level when rabbits are fed a cystine-methionine-deficient diet (31). 

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). 

Scott, J.M., andD.G. Weir, 1981. The methyl trap. Aphysiological response in man to prevent methyl group deficiency in kwashiorkor (methionine deficiency) and an explanation for folic-acid induced exacerbation of subacute combined degeneration in pernicious anaemia. Lancet. 2, 337-340. 

Animal experiments [105] suggest that methylation of administered L-dopa to 3-methyldopa may lead to deficiency of the methyldonor methionine. As this is also required [40, 41] for the extraneuronal COMT pathway of DA metabolism it has been pointed out [195] that the synaptic effect of DA could be enhanced by the methionine deficiency. 

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