Methionine residues as endogenous antioxidants in proteins
Cysteine and essential amino acid ar the 2 sulfur-containing residues usually found in proteins. amino acid residues perform within the chemical change cycle of the many enzymes, and that they will type disulfide bonds that contribute to macromolecule structure. In distinction, the precise functions of essential amino acid residues don’t seem to be best-known. we have a tendency to propose that essential amino acid residues represent a crucial inhibitor psychoanalytic process. a range of oxidants react without delay with essential amino acid to make essential amino acid sulfoxide, and surface exposed essential amino acid residues produce a particularly high concentration of chemical, out there as associate degree economical chemical agent scavenger. Reduction back to essential amino acid by essential amino acid sulfoxide reductases would enable the inhibitor system to perform catalytically. The impact of oxide exposure upon aminoalkanoic acid synthetase from escherichia was studied as associate degree in vitro model system. Eight of the sixteen essential amino acid residues might be change with very little impact on chemical change activity of the catalyst. The reactive essential amino acid residues were found to be comparatively surface exposed, whereas the intact residues were typically buried at intervals the core of the macromolecule. what is more, the inclined residues were physically organized in associate degree array that guarded the doorway to the site. [1]
Methionine oxidation and aging
It is well established that a lot of organic compound residues of proteins are at risk of oxidization by numerous kinds of reactive element species (ROS), which oxidatively changed proteins accumulate throughout aging, aerophilic stress, and in a very variety of age-related diseases. essential amino acid residues and aminoalkanoic acid residues of proteins are significantly sensitive to oxidization by ROS. However, in contrast to oxidization of different organic compound residues, the oxidization of those sulfur amino acids is reversible. oxidization of essential amino acid residues ends up in the formation of each R- and S-stereoisomers of methionine sulfoxide (MetO) and most cells contain stereospecific methionine sulfoxide reductases (Msr’s) that catalyse the thioredoxin-dependent reduction of MetO residues back to methionine residues. we have a tendency to summarize here results of studies, by several employees, showing that the MetO content of proteins will increase with age in a very variety of various aging models, as well as replicative senescence and corpuscle aging, however not in mouse tissues throughout aging. The amendment in levels of MetO might mirror alterations in anybody or additional of the many totally different mechanisms, as well as (i) a rise within the rate of ROS generation; (ii) a decrease in the inhibitor capacity; (iii) a decrease in chemical action activities that preferentially degrade change proteins; or (iv) a decrease in the ability to convert MetO residues back to Met residues, due either to a right away loss of Msr accelerator levels or indirectly to a loss within the availableness of the reducing equivalents (thioredoxin, thioredoxin enzyme, NADPH generation) concerned. The importance of Msr activity is highlighted by the very fact that aging is related to a loss of Msr activities in a very variety of animal tissues, and mutations in mice resulting in a decrease within the Msr levels result in a decrease in the most life, whereas overexpression of Msr ends up in a dramatic increase within the most life. [2]
Methionine metabolism in mammals. Adaptation to methionine excess.
We conducted a scientific analysis of the results of accelerating levels of dietary essential amino acid on the metabolites and enzymes of essential amino acid metabolism in rat liver. vital decreases in viscus concentrations of alkaloid and aminoalkanoic acid occurred once the dietary essential amino acid was raised from zero.3 to 1.0%. we tend to ascertained accumulated concentrations of S-adenosylhomocysteine in livers of rats fed one.5% essential amino acid and of S-adenosylmethionine and essential amino acid only the diet contained three.0% essential amino acid. essential amino acid supplementation resulted in diminished viscus levels of methyltetrahydrofolate-homocysteine methyltransferase and accumulated levels of essential amino acid adenosyltransferase, betaine-homocysteine methyltransferase, and cystathionine synthase. we tend to used these information to simulate the restrictive locus shaped by the enzymes that metabolise homocysteine in livers of rats fed zero.3% essential amino acid, 1.5% essential amino acid, and 3.0% essential amino acid. compared to the model for the zero.3% essential amino acid diet cluster, the model for the three.0% essential amino acid animals demonstrates a 12-fold increase within the synthesis of cystathionine, a one hundred and fiftieth increase in flow through the alkaloid reaction, and a 550% increase in total metabolism of homocysteine. The concentrations of substrates and different metabolites square measure vital determinants of this apparent adaptation. [3]
Dietary methionine influences therapy in mouse cancer models and alters human metabolism
Nutrition exerts sizeable effects on health, and dietary interventions are unremarkably accustomed treat diseases of metabolic aetiology. though cancer contains a substantial metabolic component1, the principles that outline whether or not nutrition is also accustomed influence outcomes of cancer are unclear2. still, it’s established that targeting metabolic pathways with medicine agents or radiation will typically result in controlled therapeutic outcomes. against this, whether or not specific dietary interventions will influence the metabolic pathways that are targeted in commonplace cancer therapies isn’t known . Here we tend to show that dietary restriction of the essential organic compound methionine—the reduction of that has anti-ageing and anti-obesogenic properties—influences cancer outcome, through controlled and duplicatable changes to one-carbon metabolism. This pathway metabolizes essential amino acid and is that the target of a range of cancer interventions that involve therapy and radiation. essential amino acid restriction made therapeutic responses in 2 patient-derived heterograft models of chemotherapy-resistant RAS-driven large intestine cancer, and in an exceedingly mouse model of autochthonous soft-tissue malignant neoplastic disease driven by a G12D mutation in KRAS and knockout of p53 (KrasG12D/+;Trp53−/−) that’s proof against radiation. Metabolomics disclosed that the therapeutic mechanisms operate via tumour-cell-autonomous effects on flux through one-carbon metabolism that affects oxidation-reduction and ester metabolism—and therefore move with the cancer drug or radiation intervention. in an exceedingly controlled and tolerated feeding study in humans, essential amino acid restriction resulted in effects on general metabolism that were the same as those obtained in mice. These findings offer proof that a targeted dietary manipulation will specifically have an effect on tumour-cell metabolism to mediate broad aspects of cancer outcome. [4]
Effect of L-Dopa in Replacing Dl-Methionine on the Performance of Broiler Chickens
The Brocadopa found in bush seed, once gift with alternative antinutritional factors, has been involved on nutritionary disorders of monogastric animals. it’s conjointly supposed to influence muscular development. However, data on its result on essential amino acid utilization is scanty. Therefore, the result of Brocadopa on growth performance and its replacement for DL-methionine in broiler chickens was investigated. [5]
Reference
[1] Levine, R.L., Mosoni, L., Berlett, B.S. and Stadtman, E.R., 1996. Methionine residues as endogenous antioxidants in proteins. Proceedings of the National Academy of Sciences, 93(26), pp.15036-15040. (Web Link)
[2] Stadtman, E.R., Van Remmen, H., Richardson, A., Wehr, N.B. and Levine, R.L., 2005. Methionine oxidation and aging. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 1703(2), pp.135-140. (Web Link)
[3] Finkelstein, J.D. and Martin, J.J., 1986. Methionine metabolism in mammals. Adaptation to methionine excess. Journal of Biological Chemistry, 261(4), pp.1582-1587. (Web Link)
[4] Dietary methionine influences therapy in mouse cancer models and alters human metabolism
Xia Gao, Sydney M. Sanderson, Ziwei Dai, Michael A. Reid, Daniel E. Cooper, Min Lu, John P. Richie Jr, Amy Ciccarella, Ana Calcagnotto, Peter G. Mikhael, Samantha J. Mentch, Juan Liu, Gene Ables, David G. Kirsch, David S. Hsu, Sailendra N. Nichenametla & Jason W. Locasale
Nature (2019) (Web Link)
[5] Omidiwura, B. R. O. (2019) “Effect of L-Dopa in Replacing Dl-Methionine on the Performance of Broiler Chickens”, Journal of Experimental Agriculture International, 29(2), pp. 1-8. doi: 10.9734/JEAI/2019/45401. (Web Link)