Como é sabido, as proteínas são compostas por grandes cadeias de aminoácidos, sendo que dos 20 aminoácidos existentes, alguns deles temos de obter a partir da alimentação. Dois desses aminoácidos, a metionina (MET) e a cisteína (CIS), são chamados de aminoácidos sulfurados por conterem enxofre. Para cada um desses aminoácidos temos necessidades diferentes e embora se pense que a maioria dos aminoácidos sejam seguros quando ingeridos nos níveis normais, existem algumas evidências que sugerem que uma ingestão elevada de MET e CIS esteja associada a riscos para a saúde .
Em modelo animal, níveis elevados de aminoácidos sulfurados estão associados a inibição do crescimento e um risco elevado de doenças cardiometabólicas, incluindo doenças cardiovasculares e diabetes tipo 2. Estes e outros estudos sugerem que a MET e a CIS possam ser considerados como dos aminoácidos mais tóxicos, com potenciais riscos para várias doenças crónicas . Por outro lado, vários estudos em modelo animal têm mostrado que dietas com restrição de aminoácidos sulfurados (SAAR) poderão ser benéficas a atrasar o processo de envelhecimento e a inibir o desenvolvimento de doenças relacionadas com o envelhecimento .
A restrição de metionina tem sido estudada em estudos pré-clínicos pelos seus efeitos no aumento da longevidade e melhoria da saúde metabólica, incluindo diminuição de peso e adiposidade, diminuição da resistência à insulina e melhorias nos marcadores da insulina, glicose, leptina e adiponectina . Uma revisão sobre os efeitos da restrição de aminoácidos sulfurados (metionina e cisteína) em animais mostrou que esta esteve associada a um aumento da longevidade (restrição de 80% aumentou 44% a longevidade), diminuição do risco de doenças crónicas, melhorias metabólicas (peso, IGF-1, glicémia, insulina, etc.) e diminuição do stress oxidativo .
Um estudo que incluiu 11576 participantes sugere que dietas com níveis elevados de metionina e cisteína possam aumentar o risco de doenças cardiometabólicas. De acordo com os resultados, aqueles que fizeram uma ingestão superior de MET e CIS tiveram um aumento dos níveis de fatores de risco de doenças cardiometabólicas, tais como colesterol, triglicéridos, proteína C-reativa, ácido úrico, glicose, insulina e hemoglobina glicada. O estudo mostrou também que na população estudada dos EUA, a ingestão de MET e CIS é cerca de 2,5 vezes superior da necessidade média necessária, dando-nos conta também que dietas pobres em aminoácidos sulfurados têm maior quantidade de proteína de origem vegetal do que animal. Por outras palavras, dietas de base vegetal são naturalmente baixas em MET e CIS .
Sendo um dos nutrientes essenciais, a ingestão de referência populacional (PRI) de MET e CIS são de 12,2 mg/kg/dia no caso da metionina e 6,6 mg/kg/dia no caso da cisteína. O aminoácido metionina encontra-se naturalmente presente em grandes concentrações em alimentos de origem animal como: peixe, galinha, porco, queijo, peru, carne vermelha, ovos, entre outros. Por outro lado, uma dieta de base vegetal, especialmente no caso das veganas, é naturalmente baixa em metionina .
Também relativamente ao cancro, a restrição de metionina poderá ser eficaz a inibir o seu desenvolvimento. A metionina é um aminoácido sulfurado essencial que participa na síntese de proteínas, metilação do ADN e síntese de poliaminas. É o primeiro aminoácido na cadeia de qualquer proteína. A metionina pode também ser obtido endogenamente a partir da regeneração da homocisteína, na qual participam também a vitamina B12 e o folato. No entanto, as células de cancro não têm a enzima responsável por produzir metionina a partir de homocisteína, o que as torna dependentes de fontes externas (alimentação) do aminoácido para a sua sobrevivência e proliferação .
Por esse motivo, a restrição de metionina poderá ser uma forma de explorar essa vulnerabilidade das células de cancro e inibir o seu crescimento, além de poder também interagir com tratamentos que afetam a mesma via metabólica, tal como a quimioterapia, e melhorar os seus resultados. Vários estudos in vitro e in vivo sugerem que a restrição de metionina é capaz de destruir seletivamente as células de cancro, inibir o seu crescimento e aumentar a esperança de vida saudável . Em modelo animal, a restrição de metionina sozinha ou em combinação com algumas quimioterapias tem mostrado efeitos promissores no tratamento de cancros como sarcoma, cólon e próstata, além de poder inibir a metastização de células de cancro .
Um estudo reforça a tese de que a restrição de metionina poderá ser eficaz no tratamento de alguns cancros, tendo mostrado que a mesma foi eficaz a inibir o crescimento de tumores em modelo animal e humano. Numa primeira fase do estudo, os investigadores mostraram que uma dieta com restrição de metionina foi capaz de levar a alterações metabólicas em ratos nas vias dependentes de metionina. De seguida aplicaram uma dieta com restrição de metionina em animais com cancro colorretal e animais com sarcoma. No primeiro caso (cancro colorretal) os investigadores utilizaram uma dose de quimioterapia baixa que só por si não teve efeitos no desenvolvimento do cancro. Quando combinaram esse tratamento com restrição de metionina houve uma inibição muito significativa do crescimento tumoral. No caso do sarcoma, foram observados os mesmos efeitos quanto combinada com radioterapia.
Por último, como prova de conceito, os investigadores aplicaram uma dieta com restrição de cerca de 83% de metionina em 6 voluntários humanos saudáveis ao longo de 3 semanas. Ao fim desse tempo foram observadas alterações metabólicas em vias dependentes de metionina semelhantes às observadas em animais, o que sugere que se obtenham os mesmos resultados no tratamento de cancro. Este estudo clínico piloto mostrou também que é possível fazer uma dieta com restrição de metionina sem risco de toxicidade, sendo que os níveis de metionina utilizados no estudo podem ser obtidos em dietas veganas ou algumas versões mediterrânicas .
Este estudo é de natureza preliminar, pelo que terão de ser realizados mais estudos que confirmem estes resultados. Além disso, não é possível extrapolar os mesmos para outros tipos de cancro, uma vez que estes poderão ter mecanismos diferentes e serem vulneráveis a outras intervenções nutricionais como restrição de glicose ou outras. No entanto, são resultados promissores que apontam no sentido de uma maior importância que terá a dieta no tratamento de alguns cancros.
Uma dieta de base vegetal, especialmente no caso das veganas, é naturalmente baixa em metionina. Nesse sentido, dietas veganas poderão ser uma forma eficaz de controlar o crescimento de alguns cancros .
Referências:
{1793304:EREIA47L},{1793304:9U3M3M6G};{1793304:EREIA47L},{1793304:6B34JG2W},{1793304:VMW3VIWE},{1793304:5TWH4ECZ},{1793304:IKIU4GCF};{1793304:HKHRSBIP},{1793304:PJEK75AY};{1793304:IWAH8FPD},{1793304:WZJLJIP3},{1793304:WPBRNNPE},{1793304:BK47T9AQ},{1793304:X5ZHE2W5},{1793304:WXKLSDHW};{1793304:55FXT2Y8};{1793304:LRRMW5NH};{1793304:HKHRSBIP};{1793304:HKHRSBIP};{1793304:HKHRSBIP};{1793304:H69WIWP8};{1793304:TWHEU3I3};{1793304:HKHRSBIP}
vancouver
default
asc
no
7577
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-146309c457f02e3289dc8b52517fc2c3%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22WXKLSDHW%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Ables%20et%20al.%22%2C%22parsedDate%22%3A%222012%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EAbles%20GP%2C%20Perrone%20CE%2C%20Orentreich%20D%2C%20Orentreich%20N.%20Methionine-restricted%20C57BL%5C%2F6J%20mice%20are%20resistant%20to%20diet-induced%20obesity%20and%20insulin%20resistance%20but%20have%20low%20bone%20density.%20PLoS%20ONE.%202012%3B7%2812%29%3Ae51357.%3C%5C%2Fdiv%3E%5Cn%20%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Methionine-restricted%20C57BL%5C%2F6J%20mice%20are%20resistant%20to%20diet-induced%20obesity%20and%20insulin%20resistance%20but%20have%20low%20bone%20density%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gene%20P.%22%2C%22lastName%22%3A%22Ables%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Carmen%20E.%22%2C%22lastName%22%3A%22Perrone%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%22%2C%22lastName%22%3A%22Orentreich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Norman%22%2C%22lastName%22%3A%22Orentreich%22%7D%5D%2C%22abstractNote%22%3A%22Dietary%20methionine%20restriction%20%28MR%29%20extends%20lifespan%2C%20an%20effect%20associated%20with%20reduction%20of%20body%20weight%20gain%2C%20and%20improvement%20of%20insulin%20sensitivity%20in%20mice%20and%20rats%20as%20a%20result%20of%20metabolic%20adaptations%20in%20liver%2C%20adipose%20tissue%20and%20skeletal%20muscle.%20To%20test%20whether%20MR%20confers%20resistance%20to%20adiposity%20and%20insulin%20resistance%2C%20C57BL%5C%2F6J%20mice%20were%20fed%20a%20high%20fat%20diet%20%28HFD%29%20containing%20either%200.86%25%20methionine%20%28control%20fed%3B%20CF%29%20or%200.12%25%20methionine%20%28methionine-restricted%3B%20MR%29.%20MR%20mice%20on%20HFD%20had%20lower%20body%20weight%20gain%20despite%20increased%20food%20intake%20and%20absorption%20efficiency%20compared%20to%20their%20CF%20counterparts.%20MR%20mice%20on%20HFD%20were%20more%20glucose%20tolerant%20and%20insulin%20sensitive%20with%20reduced%20accumulation%20of%20hepatic%20triglycerides.%20In%20plasma%2C%20MR%20mice%20on%20HFD%20had%20higher%20levels%20of%20adiponectin%20and%20FGF21%20while%20leptin%20and%20IGF-1%20levels%20were%20reduced.%20Hepatic%20gene%20expression%20showed%20the%20downregulation%20of%20Scd1%20while%20Pparg%2C%20Atgl%2C%20Cd36%2C%20Jak2%20and%20Fgf21%20were%20upregulated%20in%20MR%20mice%20on%20HFD.%20Restriction%20of%20growth%20rate%20in%20MR%20mice%20on%20HFD%20was%20also%20associated%20with%20lower%20bone%20mass%20and%20increased%20plasma%20levels%20of%20the%20collagen%20degradation%20marker%20C-terminal%20telopeptide%20of%20type%201%20collagen%20%28CTX-1%29.%20It%20is%20concluded%20that%20MR%20mice%20on%20HFD%20are%20metabolically%20healthy%20compared%20to%20CF%20mice%20on%20HFD%20but%20have%20decreased%20bone%20mass.%20These%20effects%20could%20be%20associated%20with%20the%20observed%20increase%20in%20FGF21%20levels.%22%2C%22date%22%3A%222012%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1371%5C%2Fjournal.pone.0051357%22%2C%22ISSN%22%3A%221932-6203%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-04-27T16%3A18%3A07Z%22%7D%7D%2C%7B%22key%22%3A%22X5ZHE2W5%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Malloy%20et%20al.%22%2C%22parsedDate%22%3A%222013-11%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EMalloy%20VL%2C%20Perrone%20CE%2C%20Mattocks%20DAL%2C%20Ables%20GP%2C%20Caliendo%20NS%2C%20Orentreich%20DS%2C%20et%20al.%20Methionine%20restriction%20prevents%20the%20progression%20of%20hepatic%20steatosis%20in%20leptin-deficient%20obese%20mice.%20Metab%20Clin%20Exp.%202013%20Nov%3B62%2811%29%3A1651%26%23x2013%3B61.%3C%5C%2Fdiv%3E%5Cn%20%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Methionine%20restriction%20prevents%20the%20progression%20of%20hepatic%20steatosis%20in%20leptin-deficient%20obese%20mice%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Virginia%20L.%22%2C%22lastName%22%3A%22Malloy%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Carmen%20E.%22%2C%22lastName%22%3A%22Perrone%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dwight%20A.%20L.%22%2C%22lastName%22%3A%22Mattocks%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gene%20P.%22%2C%22lastName%22%3A%22Ables%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nicholas%20S.%22%2C%22lastName%22%3A%22Caliendo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%20S.%22%2C%22lastName%22%3A%22Orentreich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Norman%22%2C%22lastName%22%3A%22Orentreich%22%7D%5D%2C%22abstractNote%22%3A%22OBJECTIVE%3A%20This%20study%20investigated%20the%20effects%20of%20dietary%20methionine%20restriction%20%28MR%29%20on%20the%20progression%20of%20established%20hepatic%20steatosis%20in%20the%20leptin-deficient%20ob%5C%2Fob%20mouse.%5CnMATERIAL%5C%2FMETHODS%3A%20Ten-week-old%20ob%5C%2Fob%20mice%20were%20fed%20diets%20containing%200.86%25%20%28control-fed%3B%20CF%29%20or%200.12%25%20methionine%20%28MR%29%20for%2014%20weeks.%20At%2014%20weeks%2C%20liver%20and%20fat%20were%20excised%20and%20blood%20was%20collected%20for%20analysis.%20In%20another%20study%2C%20blood%20was%20collected%20to%20determine%20in%20vivo%20triglyceride%20%28TG%29%20and%20very-low-density%20lipoprotein%20%28VLDL%29%20secretion%20rates.%20Liver%20histology%20was%20conducted%20to%20determine%20the%20severity%20of%20steatosis.%20Hepatic%20TG%2C%20free%20fatty%20acid%20levels%2C%20and%20fatty%20acid%20oxidation%20%28FAO%29%20were%20also%20measured.%20Gene%20expression%20was%20analyzed%20by%20quantitative%20PCR.%5CnRESULTS%3A%20MR%20reversed%20the%20severity%20of%20steatosis%20in%20the%20ob%5C%2Fob%20mouse.%20This%20was%20accompanied%20by%20reduced%20body%20weight%20despite%20similar%20weight-specific%20food%20intake.%20Compared%20with%20the%20CF%20group%2C%20hepatic%20TG%20levels%20were%20significantly%20reduced%20in%20response%20to%20MR%2C%20but%20adipose%20tissue%20weight%20was%20not%20decreased.%20MR%20reduced%20insulin%20and%20HOMA%20ratios%20but%20increased%20total%20and%20high-molecular-weight%20adiponectin%20levels.%20Scd1%20gene%20expression%20was%20significantly%20downregulated%2C%20while%20Acadvl%2C%20Hadha%2C%20and%20Hadhb%20were%20upregulated%20in%20MR%2C%20corresponding%20with%20increased%20%5Cu03b2-hydroxybutyrate%20levels%20and%20a%20trend%20toward%20increased%20FAO.%20The%20VLDL%20secretion%20rate%20was%20also%20significantly%20increased%20in%20the%20MR%20mice%2C%20as%20were%20the%20mRNA%20levels%20of%20ApoB%20and%20Mttp.%20The%20expression%20of%20inflammatory%20markers%2C%20such%20as%20Tnf-%5Cu03b1%20and%20Ccr2%2C%20was%20also%20downregulated%20by%20MR.%5CnCONCLUSIONS%3A%20Our%20data%20indicate%20that%20MR%20reverses%20steatosis%20in%20the%20ob%5C%2Fob%20mouse%20liver%20by%20promoting%20FAO%2C%20increasing%20the%20export%20of%20lipids%2C%20and%20reducing%20obesity-related%20inflammatory%20responses.%22%2C%22date%22%3A%22Nov%202013%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.metabol.2013.06.012%22%2C%22ISSN%22%3A%221532-8600%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-04-27T16%3A17%3A42Z%22%7D%7D%2C%7B%22key%22%3A%22BK47T9AQ%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Lee%20et%20al.%22%2C%22parsedDate%22%3A%222014-04-07%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3ELee%20BC%2C%20Kaya%20A%2C%20Ma%20S%2C%20Kim%20G%2C%20Gerashchenko%20MV%2C%20Yim%20SH%2C%20et%20al.%20Methionine%20restriction%20extends%20lifespan%20of%20Drosophila%20melanogaster%20under%20conditions%20of%20low%20amino%20acid%20status.%20Nat%20Commun%20%5BInternet%5D.%202014%20Apr%207%20%5Bcited%202020%20Apr%2027%5D%3B5%3A3592.%20Available%20from%3A%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.ncbi.nlm.nih.gov%5C%2Fpmc%5C%2Farticles%5C%2FPMC4350766%5C%2F%27%3Ehttps%3A%5C%2F%5C%2Fwww.ncbi.nlm.nih.gov%5C%2Fpmc%5C%2Farticles%5C%2FPMC4350766%5C%2F%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Methionine%20restriction%20extends%20lifespan%20of%20Drosophila%20melanogaster%20under%20conditions%20of%20low%20amino%20acid%20status%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Byung%20Cheon%22%2C%22lastName%22%3A%22Lee%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alaattin%22%2C%22lastName%22%3A%22Kaya%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Siming%22%2C%22lastName%22%3A%22Ma%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gwansu%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Maxim%20V.%22%2C%22lastName%22%3A%22Gerashchenko%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sun%20Hee%22%2C%22lastName%22%3A%22Yim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhen%22%2C%22lastName%22%3A%22Hu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lawrence%20G.%22%2C%22lastName%22%3A%22Harshman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vadim%20N.%22%2C%22lastName%22%3A%22Gladyshev%22%7D%5D%2C%22abstractNote%22%3A%22Reduced%20methionine%20%28Met%29%20intake%20can%20extend%20lifespan%20of%20rodents%2C%20but%20whether%20this%20regimen%20represents%20a%20general%20strategy%20for%20regulating%20aging%20has%20been%20controversial.%20Here%20we%20report%20that%20Met%20restriction%20extends%20lifespan%20in%20both%20fruit%20flies%20and%20yeast%2C%20and%20that%20this%20effect%20requires%20low%20amino%20acid%20status.%20Met%20restriction%20in%20Drosophila%20mimicks%20the%20effect%20of%20dietary%20restriction%20and%20is%20associated%20with%20decreased%20reproduction.%20However%2C%20under%20conditions%20of%20high%20amino%20acid%20status%2C%20Met%20restriction%20is%20ineffective%20and%20the%20trade-off%20between%20longevity%20and%20reproduction%20is%20not%20observed.%20Overexpression%20of%20InRDN%20or%20Tsc2%20inhibits%20lifespan%20extension%20by%20Met%20restriction%2C%20suggesting%20the%20role%20of%20TOR%20signaling%20in%20the%20Met%20control%20of%20longevity.%20Overall%2C%20this%20study%20defines%20the%20specific%20roles%20of%20Met%20and%20amino%20acid%20imbalance%20in%20aging%20and%20suggests%20that%20Met%20restiction%20is%20a%20general%20strategy%20for%20lifespan%20extension.%22%2C%22date%22%3A%222014-4-07%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1038%5C%2Fncomms4592%22%2C%22ISSN%22%3A%222041-1723%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.ncbi.nlm.nih.gov%5C%2Fpmc%5C%2Farticles%5C%2FPMC4350766%5C%2F%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-04-27T16%3A16%3A51Z%22%7D%7D%2C%7B%22key%22%3A%22LRRMW5NH%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Dong%20et%20al.%22%2C%22parsedDate%22%3A%222020-02-01%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EDong%20Z%2C%20Gao%20X%2C%20Chinchilli%20VM%2C%20Sinha%20R%2C%20Muscat%20J%2C%20Winkels%20RM%2C%20et%20al.%20Association%20of%20sulfur%20amino%20acid%20consumption%20with%20cardiometabolic%20risk%20factors%3A%20Cross-sectional%20findings%20from%20NHANES%20III.%20EClinicalMedicine%20%5BInternet%5D.%202020%20Feb%201%20%5Bcited%202020%20Mar%2026%5D%3B19.%20Available%20from%3A%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.thelancet.com%5C%2Fjournals%5C%2Feclinm%5C%2Farticle%5C%2FPIIS2589-5370%2819%2930257-3%5C%2Fabstract%27%3Ehttps%3A%5C%2F%5C%2Fwww.thelancet.com%5C%2Fjournals%5C%2Feclinm%5C%2Farticle%5C%2FPIIS2589-5370%2819%2930257-3%5C%2Fabstract%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Association%20of%20sulfur%20amino%20acid%20consumption%20with%20cardiometabolic%20risk%20factors%3A%20Cross-sectional%20findings%20from%20NHANES%20III%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhen%22%2C%22lastName%22%3A%22Dong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiang%22%2C%22lastName%22%3A%22Gao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vernon%20M.%22%2C%22lastName%22%3A%22Chinchilli%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Raghu%22%2C%22lastName%22%3A%22Sinha%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Joshua%22%2C%22lastName%22%3A%22Muscat%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Renate%20M.%22%2C%22lastName%22%3A%22Winkels%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22John%20P.%22%2C%22lastName%22%3A%22Richie%22%7D%5D%2C%22abstractNote%22%3A%22%3Ch2%3EAbstract%3C%5C%2Fh2%3E%3Ch3%3EBackground%3C%5C%2Fh3%3E%3Cp%3EAn%20average%20adult%20American%20consumes%20sulfur%20amino%20acids%20%28SAA%29%20at%20levels%20far%20above%20the%20Estimated%20Average%20Requirement%20%28EAR%29%20and%20recent%20preclinical%20data%20suggest%20that%20higher%20levels%20of%20SAA%20intake%20may%20be%20associated%20with%20a%20variety%20of%20aging-related%20chronic%20diseases.%20However%2C%20there%20are%20little%20data%20regarding%20the%20relationship%20between%20SAA%20intake%20and%20chronic%20disease%20risk%20in%20humans.%20The%20aim%20of%20this%20study%20was%20to%20examine%20the%20associations%20between%20consumption%20of%20SAA%20and%20risk%20factors%20for%20cardiometabolic%20diseases.%3C%5C%2Fp%3E%3Ch3%3EMethods%3C%5C%2Fh3%3E%3Cp%3EThe%20sample%20included%2011%2C576%20adult%20participants%20of%20the%20Third%20National%20Examination%20and%20Nutritional%20Health%20Survey%20%28NHANES%20III%29%20Study%20%281988%5Cu20131994%29.%20The%20primary%20outcome%20was%20cardiometabolic%20disease%20risk%20score%20%28composite%20risk%20factor%20based%20on%20blood%20cholesterol%2C%20triglycerides%2C%20HDL%2C%20C-reactive%20protein%20%28CRP%29%2C%20uric%20acid%2C%20glucose%2C%20blood%20urea%20nitrogen%20%28BUN%29%2C%20glycated%20hemoglobin%2C%20insulin%2C%20and%20eGFR%29.%20Group%20differences%20in%20risk%20score%20by%20quintiles%20of%20energy-adjusted%20total%20SAA%2C%20methionine%20%28Met%29%2C%20and%20cysteine%20%28Cys%29%20intake%20were%20determined%20by%20multiple%20linear%20regression%20after%20adjusting%20for%20age%2C%20sex%2C%20BMI%2C%20smoking%2C%20alcohol%20intake%2C%20and%20dietary%20factors.%20We%20further%20examined%20for%20associations%20between%20SAA%20intake%20and%20individual%20risk%20factors.%3C%5C%2Fp%3E%3Ch3%3EFindings%3C%5C%2Fh3%3E%3Cp%3EMean%20SAA%20consumption%20was%20%3E%202.5-fold%20higher%20than%20the%20EAR.%20After%20multivariable%20adjustment%2C%20higher%20intake%20of%20SAA%2C%20Met%2C%20and%20Cys%20were%20associated%20with%20significant%20increases%20in%20composite%20cardiometabolic%20disease%20risk%20scores%2C%20independent%20of%20protein%20intake%2C%20and%20with%20several%20individual%20risk%20factors%20including%20serum%20cholesterol%2C%20glucose%2C%20uric%20acid%2C%20BUN%2C%20and%20insulin%20and%20glycated%20hemoglobin%20%28%3Ci%3Ep%3C%5C%2Fi%3E%20%3C%200.01%29.%3C%5C%2Fp%3E%3Ch3%3EInterpretation%3C%5C%2Fh3%3E%3Cp%3EOverall%2C%20our%20findings%20suggest%20that%20diets%20lower%20in%20SAA%20%28close%20to%20the%20EAR%29%20are%20associated%20with%20reduced%20risk%20for%20cardiometabolic%20diseases.%20Low%20SAA%20dietary%20patterns%20rely%20on%20plant-derived%20protein%20sources%20over%20meat%20derived%20foods.%20Given%20the%20high%20intake%20of%20SAA%20among%20most%20adults%2C%20our%20findings%20may%20have%20important%20public%20health%20implications%20for%20chronic%20disease%20prevention.%3C%5C%2Fp%3E%3Ch3%3EFunding%3C%5C%2Fh3%3E%3Cp%3EThis%20study%20does%20not%20have%20any%20funding.%3C%5C%2Fp%3E%22%2C%22date%22%3A%222020%5C%2F02%5C%2F01%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.eclinm.2019.100248%22%2C%22ISSN%22%3A%222589-5370%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.thelancet.com%5C%2Fjournals%5C%2Feclinm%5C%2Farticle%5C%2FPIIS2589-5370%2819%2930257-3%5C%2Fabstract%22%2C%22collections%22%3A%5B%22RFSX9J4X%22%5D%2C%22dateModified%22%3A%222020-03-26T21%3A33%3A10Z%22%7D%7D%2C%7B%22key%22%3A%22WZJLJIP3%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Malloy%20et%20al.%22%2C%22parsedDate%22%3A%222006-08%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EMalloy%20VL%2C%20Krajcik%20RA%2C%20Bailey%20SJ%2C%20Hristopoulos%20G%2C%20Plummer%20JD%2C%20Orentreich%20N.%20Methionine%20restriction%20decreases%20visceral%20fat%20mass%20and%20preserves%20insulin%20action%20in%20aging%20male%20Fischer%20344%20rats%20independent%20of%20energy%20restriction.%20Aging%20Cell.%202006%20Aug%3B5%284%29%3A305%26%23x2013%3B14.%3C%5C%2Fdiv%3E%5Cn%20%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Methionine%20restriction%20decreases%20visceral%20fat%20mass%20and%20preserves%20insulin%20action%20in%20aging%20male%20Fischer%20344%20rats%20independent%20of%20energy%20restriction%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Virginia%20L.%22%2C%22lastName%22%3A%22Malloy%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rozlyn%20A.%22%2C%22lastName%22%3A%22Krajcik%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Steven%20J.%22%2C%22lastName%22%3A%22Bailey%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22George%22%2C%22lastName%22%3A%22Hristopoulos%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jason%20D.%22%2C%22lastName%22%3A%22Plummer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Norman%22%2C%22lastName%22%3A%22Orentreich%22%7D%5D%2C%22abstractNote%22%3A%22Reduced%20dietary%20methionine%20intake%20%280.17%25%20methionine%2C%20MR%29%20and%20calorie%20restriction%20%28CR%29%20prolong%20lifespan%20in%20male%20Fischer%20344%20rats.%20Although%20the%20mechanisms%20are%20unclear%2C%20both%20regimens%20feature%20lower%20body%20weight%20and%20reductions%20in%20adiposity.%20Reduced%20fat%20deposition%20in%20CR%20is%20linked%20to%20preservation%20of%20insulin%20responsiveness%20in%20older%20animals.%20These%20studies%20examine%20the%20relationship%20between%20insulin%20responsiveness%20and%20visceral%20fat%20in%20MR%20and%20test%20whether%2C%20despite%20lower%20food%20intake%20observed%20in%20MR%20animals%2C%20decreased%20visceral%20fat%20accretion%20and%20preservation%20of%20insulin%20sensitivity%20is%20not%20secondary%20to%20CR.%20Accordingly%2C%20rats%20pair%20fed%20%28pf%29%20control%20diet%20%280.86%25%20methinone%2C%20CF%29%20to%20match%20the%20food%20intake%20of%20MR%20for%2080%20weeks%20exhibit%20insulin%2C%20glucose%2C%20and%20leptin%20levels%20similar%20to%20control-fed%20animals%20and%20comparable%20amounts%20of%20visceral%20fat.%20Conversely%2C%20MR%20rats%20show%20significantly%20reduced%20visceral%20fat%20compared%20to%20CF%20and%20PF%20with%20concomitant%20decreases%20in%20basal%20insulin%2C%20glucose%2C%20and%20leptin%2C%20and%20increased%20adiponectin%20and%20triiodothyronine.%20Daily%20energy%20expenditure%20in%20MR%20animals%20significantly%20exceeds%20that%20of%20both%20PF%20and%20CF.%20In%20a%20separate%20cohort%2C%20insulin%20responses%20of%20older%20MR%20animals%20as%20measured%20by%20oral%20glucose%20challenge%20are%20similar%20to%20young%20animals.%20Longitudinal%20assessments%20of%20MR%20and%20CF%20through%20112%20weeks%20of%20age%20reveal%20that%20MR%20prevents%20age-associated%20increases%20in%20serum%20lipids.%20By%2016%20weeks%2C%20MR%20animals%20show%20a%2040%25%20reduction%20in%20insulin-like%20growth%20factor-1%20%28IGF-1%29%20that%20is%20sustained%20throughout%20life%3B%20CF%20IGF-1%20levels%20decline%20much%20later%2C%20beginning%20at%20112%20weeks.%20Collectively%2C%20the%20results%20indicate%20that%20MR%20reduces%20visceral%20fat%20and%20preserves%20insulin%20activity%20in%20aging%20rats%20independent%20of%20energy%20restriction.%22%2C%22date%22%3A%22Aug%202006%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1111%5C%2Fj.1474-9726.2006.00220.x%22%2C%22ISSN%22%3A%221474-9718%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-02-10T13%3A28%3A07Z%22%7D%7D%2C%7B%22key%22%3A%22WPBRNNPE%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Perrone%20et%20al.%22%2C%22parsedDate%22%3A%222013-07%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EPerrone%20CE%2C%20Malloy%20VL%2C%20Orentreich%20DS%2C%20Orentreich%20N.%20Metabolic%20adaptations%20to%20methionine%20restriction%20that%20benefit%20health%20and%20lifespan%20in%20rodents.%20Exp%20Gerontol.%202013%20Jul%3B48%287%29%3A654%26%23x2013%3B60.%3C%5C%2Fdiv%3E%5Cn%20%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Metabolic%20adaptations%20to%20methionine%20restriction%20that%20benefit%20health%20and%20lifespan%20in%20rodents%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Carmen%20E.%22%2C%22lastName%22%3A%22Perrone%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Virginia%20L.%22%2C%22lastName%22%3A%22Malloy%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%20S.%22%2C%22lastName%22%3A%22Orentreich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Norman%22%2C%22lastName%22%3A%22Orentreich%22%7D%5D%2C%22abstractNote%22%3A%22Restriction%20of%20dietary%20methionine%20by%2080%25%20slows%20the%20progression%20of%20aged-related%20diseases%20and%20prolongs%20lifespan%20in%20rodents.%20A%20salient%20feature%20of%20the%20methionine%20restriction%20phenotype%20is%20the%20significant%20reduction%20of%20adipose%20tissue%20mass%2C%20which%20is%20associated%20with%20improvement%20of%20insulin%20sensitivity.%20These%20beneficial%20effects%20of%20MR%20involve%20a%20host%20of%20metabolic%20adaptations%20leading%20to%20increased%20mitochondrial%20biogenesis%20and%20function%2C%20elevated%20energy%20expenditure%2C%20changes%20of%20lipid%20and%20carbohydrate%20homeostasis%2C%20and%20decreased%20oxidative%20damage%20and%20inflammation.%20This%20review%20summarizes%20observations%20from%20MR%20studies%20and%20provides%20insight%20about%20potential%20mediators%20of%20tissue-specific%20responses%20associated%20with%20MR%27s%20favorable%20metabolic%20effects%20that%20contribute%20to%20health%20and%20lifespan%20extension.%22%2C%22date%22%3A%22Jul%202013%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.exger.2012.07.005%22%2C%22ISSN%22%3A%221873-6815%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-02-10T13%3A27%3A44Z%22%7D%7D%2C%7B%22key%22%3A%22IWAH8FPD%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Orentreich%20et%20al.%22%2C%22parsedDate%22%3A%221993-02%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EOrentreich%20N%2C%20Matias%20JR%2C%20DeFelice%20A%2C%20Zimmerman%20JA.%20Low%20methionine%20ingestion%20by%20rats%20extends%20life%20span.%20J%20Nutr.%201993%20Feb%3B123%282%29%3A269%26%23x2013%3B74.%3C%5C%2Fdiv%3E%5Cn%20%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Low%20methionine%20ingestion%20by%20rats%20extends%20life%20span%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22N.%22%2C%22lastName%22%3A%22Orentreich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20R.%22%2C%22lastName%22%3A%22Matias%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22DeFelice%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20A.%22%2C%22lastName%22%3A%22Zimmerman%22%7D%5D%2C%22abstractNote%22%3A%22Dietary%20energy%20restriction%20has%20been%20a%20widely%20used%20means%20of%20experimentally%20extending%20mammalian%20life%20span.%20We%20report%20here%20that%20lifelong%20reduction%20in%20the%20concentration%20of%20a%20single%20dietary%20component%2C%20the%20essential%20amino%20acid%20L-methionine%2C%20from%200.86%20to%200.17%25%20of%20the%20diet%20results%20in%20a%2030%25%20longer%20life%20span%20of%20male%20Fischer%20344%20rats.%20Methionine%20restriction%20completely%20abolished%20growth%2C%20although%20food%20intake%20was%20actually%20greater%20on%20a%20body%20weight%20basis.%20Studies%20of%20energy%20consumption%20in%20early%20life%20indicated%20that%20the%20energy%20intake%20of%200.17%25%20methionine-fed%20animals%20was%20near%20normal%20for%20animals%20of%20their%20size%2C%20although%20consumption%20per%20animal%20was%20below%20that%20of%20the%20much%20larger%200.86%25%20methionine-fed%20rats.%20Increasing%20the%20energy%20intake%20of%20rats%20fed%200.17%25%20methionine%20failed%20to%20increase%20their%20rate%20of%20growth%2C%20whereas%20restricting%200.85%25%20methionine-fed%20rats%20to%20the%20food%20intake%20of%200.17%25%20methionine-fed%20animals%20did%20not%20materially%20reduce%20growth%2C%20indicating%20that%20food%20restriction%20was%20not%20a%20factor%20in%20life%20span%20extension%20in%20these%20experiments.%20The%20biochemically%20well-defined%20pathways%20of%20methionine%20metabolism%20and%20utilization%20offer%20the%20potential%20for%20uncovering%20the%20precise%20mechanism%28s%29%20underlying%20this%20specific%20dietary%20restriction-related%20extension%20of%20life%20span.%22%2C%22date%22%3A%22Feb%201993%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1093%5C%2Fjn%5C%2F123.2.269%22%2C%22ISSN%22%3A%220022-3166%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-02-10T13%3A27%3A14Z%22%7D%7D%2C%7B%22key%22%3A%22PJEK75AY%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Miller%20et%20al.%22%2C%22parsedDate%22%3A%222005-06%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EMiller%20RA%2C%20Buehner%20G%2C%20Chang%20Y%2C%20Harper%20JM%2C%20Sigler%20R%2C%20Smith-Wheelock%20M.%20Methionine-deficient%20diet%20extends%20mouse%20lifespan%2C%20slows%20immune%20and%20lens%20aging%2C%20alters%20glucose%2C%20T4%2C%20IGF-I%20and%20insulin%20levels%2C%20and%20increases%20hepatocyte%20MIF%20levels%20and%20stress%20resistance.%20Aging%20Cell.%202005%20Jun%3B4%283%29%3A119%26%23x2013%3B25.%3C%5C%2Fdiv%3E%5Cn%20%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Methionine-deficient%20diet%20extends%20mouse%20lifespan%2C%20slows%20immune%20and%20lens%20aging%2C%20alters%20glucose%2C%20T4%2C%20IGF-I%20and%20insulin%20levels%2C%20and%20increases%20hepatocyte%20MIF%20levels%20and%20stress%20resistance%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Richard%20A.%22%2C%22lastName%22%3A%22Miller%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gretchen%22%2C%22lastName%22%3A%22Buehner%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yayi%22%2C%22lastName%22%3A%22Chang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20M.%22%2C%22lastName%22%3A%22Harper%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Robert%22%2C%22lastName%22%3A%22Sigler%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%22%2C%22lastName%22%3A%22Smith-Wheelock%22%7D%5D%2C%22abstractNote%22%3A%22A%20diet%20deficient%20in%20the%20amino%20acid%20methionine%20has%20previously%20been%20shown%20to%20extend%20lifespan%20in%20several%20stocks%20of%20inbred%20rats.%20We%20report%20here%20that%20a%20methionine-deficient%20%28Meth-R%29%20diet%20also%20increases%20maximal%20lifespan%20in%20%28BALB%5C%2FcJ%20x%20C57BL%5C%2F6%20J%29F1%20mice.%20Compared%20with%20controls%2C%20Meth-R%20mice%20have%20significantly%20lower%20levels%20of%20serum%20IGF-I%2C%20insulin%2C%20glucose%20and%20thyroid%20hormone.%20Meth-R%20mice%20also%20have%20higher%20levels%20of%20liver%20mRNA%20for%20MIF%20%28macrophage%20migration%20inhibition%20factor%29%2C%20known%20to%20be%20higher%20in%20several%20other%20mouse%20models%20of%20extended%20longevity.%20Meth-R%20mice%20are%20significantly%20slower%20to%20develop%20lens%20turbidity%20and%20to%20show%20age-related%20changes%20in%20T-cell%20subsets.%20They%20are%20also%20dramatically%20more%20resistant%20to%20oxidative%20liver%20cell%20injury%20induced%20by%20injection%20of%20toxic%20doses%20of%20acetaminophen.%20The%20spectrum%20of%20terminal%20illnesses%20in%20the%20Meth-R%20group%20is%20similar%20to%20that%20seen%20in%20control%20mice.%20Studies%20of%20the%20cellular%20and%20molecular%20biology%20of%20methionine-deprived%20mice%20may%2C%20in%20parallel%20to%20studies%20of%20calorie-restricted%20mice%2C%20provide%20insights%20into%20the%20way%20in%20which%20nutritional%20factors%20modulate%20longevity%20and%20late-life%20illnesses.%22%2C%22date%22%3A%22Jun%202005%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1111%5C%2Fj.1474-9726.2005.00152.x%22%2C%22ISSN%22%3A%221474-9718%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-02-10T13%3A23%3A34Z%22%7D%7D%2C%7B%22key%22%3A%22HKHRSBIP%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Cavuoto%20and%20Fenech%22%2C%22parsedDate%22%3A%222012-10%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3ECavuoto%20P%2C%20Fenech%20MF.%20A%20review%20of%20methionine%20dependency%20and%20the%20role%20of%20methionine%20restriction%20in%20cancer%20growth%20control%20and%20life-span%20extension.%20Cancer%20Treat%20Rev.%202012%20Oct%3B38%286%29%3A726%26%23x2013%3B36.%3C%5C%2Fdiv%3E%5Cn%20%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22A%20review%20of%20methionine%20dependency%20and%20the%20role%20of%20methionine%20restriction%20in%20cancer%20growth%20control%20and%20life-span%20extension%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Paul%22%2C%22lastName%22%3A%22Cavuoto%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%20F.%22%2C%22lastName%22%3A%22Fenech%22%7D%5D%2C%22abstractNote%22%3A%22Methionine%20is%20an%20essential%20amino%20acid%20with%20many%20key%20roles%20in%20mammalian%20metabolism%20such%20as%20protein%20synthesis%2C%20methylation%20of%20DNA%20and%20polyamine%20synthesis.%20Restriction%20of%20methionine%20may%20be%20an%20important%20strategy%20in%20cancer%20growth%20control%20particularly%20in%20cancers%20that%20exhibit%20dependence%20on%20methionine%20for%20survival%20and%20proliferation.%20Methionine%20dependence%20in%20cancer%20may%20be%20due%20to%20one%20or%20a%20combination%20of%20deletions%2C%20polymorphisms%20or%20alterations%20in%20expression%20of%20genes%20in%20the%20methionine%20de%20novo%20and%20salvage%20pathways.%20Cancer%20cells%20with%20these%20defects%20are%20unable%20to%20regenerate%20methionine%20via%20these%20pathways.%20Defects%20in%20the%20metabolism%20of%20folate%20may%20also%20contribute%20to%20the%20methionine%20dependence%20phenotype%20in%20cancer.%20Selective%20killing%20of%20methionine%20dependent%20cancer%20cells%20in%20co-culture%20with%20normal%20cells%20has%20been%20demonstrated%20using%20culture%20media%20deficient%20in%20methionine.%20Several%20animal%20studies%20utilizing%20a%20methionine%20restricted%20diet%20have%20reported%20inhibition%20of%20cancer%20growth%20and%20extension%20of%20a%20healthy%20life-span.%20In%20humans%2C%20vegan%20diets%2C%20which%20can%20be%20low%20in%20methionine%2C%20may%20prove%20to%20be%20a%20useful%20nutritional%20strategy%20in%20cancer%20growth%20control.%20The%20development%20of%20methioninase%20which%20depletes%20circulating%20levels%20of%20methionine%20may%20be%20another%20useful%20strategy%20in%20limiting%20cancer%20growth.%20The%20application%20of%20nutritional%20methionine%20restriction%20and%20methioninase%20in%20combination%20with%20chemotherapeutic%20regimens%20is%20the%20current%20focus%20of%20clinical%20studies.%22%2C%22date%22%3A%22Oct%202012%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.ctrv.2012.01.004%22%2C%22ISSN%22%3A%221532-1967%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-02-10T13%3A22%3A36Z%22%7D%7D%2C%7B%22key%22%3A%22IKIU4GCF%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Yal%5Cu00e7inkaya%20et%20al.%22%2C%22parsedDate%22%3A%222009-04%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EYal%26%23xE7%3Binkaya%20S%2C%20Unl%26%23xFC%3B%26%23xE7%3Ber%26%23xE7%3Bi%20Y%2C%20Giri%26%23x15F%3B%20M%2C%20Olga%26%23xE7%3B%20V%2C%20Do%26%23x11F%3Bru-Abbaso%26%23x11F%3Blu%20S%2C%20Uysal%20M.%20Oxidative%20and%20nitrosative%20stress%20and%20apoptosis%20in%20the%20liver%20of%20rats%20fed%20on%20high%20methionine%20diet%3A%20protective%20effect%20of%20taurine.%20Nutrition.%202009%20Apr%3B25%284%29%3A436%26%23x2013%3B44.%3C%5C%2Fdiv%3E%5Cn%20%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Oxidative%20and%20nitrosative%20stress%20and%20apoptosis%20in%20the%20liver%20of%20rats%20fed%20on%20high%20methionine%20diet%3A%20protective%20effect%20of%20taurine%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Seda%22%2C%22lastName%22%3A%22Yal%5Cu00e7inkaya%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ye%5Cu015fim%22%2C%22lastName%22%3A%22Unl%5Cu00fc%5Cu00e7er%5Cu00e7i%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Murat%22%2C%22lastName%22%3A%22Giri%5Cu015f%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vakur%22%2C%22lastName%22%3A%22Olga%5Cu00e7%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Semra%22%2C%22lastName%22%3A%22Do%5Cu011fru-Abbaso%5Cu011flu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M%5Cu00fcjdat%22%2C%22lastName%22%3A%22Uysal%22%7D%5D%2C%22abstractNote%22%3A%22OBJECTIVE%3A%20There%20are%20few%20reports%20about%20the%20direct%20toxic%20effects%20of%20hyperhomocysteinemia%20on%20the%20liver.%20We%20investigated%20oxidative%20and%20nitrosative%20stresses%20and%20apoptotic%20and%20necrotic%20changes%20in%20the%20liver%20of%20rats%20fed%20a%20high-methionine%20%28HM%29%20diet%20%282%25%2C%20w%5C%2Fw%29%20for%206%20mo.%20We%20also%20investigated%20whether%20taurine%2C%20an%20antioxidant%20amino%20acid%2C%20is%20protective%20against%20an%20HM-diet-induced%20toxicity%20in%20the%20liver.%5CnMETHODS%3A%20Lipid%20peroxide%20levels%2C%20nitrotyrosine%20formation%2C%20and%20non-enzymatic%20and%20enzymatic%20antioxidants%20were%20determined%20in%20livers%20of%20rats%20fed%20an%20HM%20diet.%20In%20addition%2C%20apoptosis-related%20proteins%2C%20proapoptotic%20Bax%20and%20antiapoptotic%20B-cell%20lymphoma-2%20expressions%2C%20apoptotic%20cell%20count%2C%20histopathologic%20appearance%20in%20the%20liver%2C%20and%20alanine%20transaminase%20and%20aspartate%20transaminase%20activities%20in%20the%20serum%20were%20investigated.%5CnRESULTS%3A%20Plasma%20homocysteine%20levels%20and%20serum%20alanine%20transaminase%20and%20aspartate%20transaminase%20activities%20were%20increased%20after%20the%20HM%20diet.%20This%20diet%20resulted%20in%20increases%20in%20lipid%20peroxide%20and%20nitrotyrosine%20levels%20and%20decreases%20in%20non-enzymatic%20and%20enzymatic%20antioxidants%20in%20liver%20homogenates%20in%20rats.%20Bax%20expression%20increased%2C%20B-cell%20lymphoma-2%20expression%20decreased%2C%20and%20apoptotic%20cell%20number%20increased%20in%20livers%20of%20rats%20fed%20an%20HM%20diet.%20Inflammatory%20reactions%2C%20microvesicular%20steatosis%2C%20and%20hepatocyte%20degeneration%20were%20observed%20in%20the%20liver%20after%20the%20HM%20diet.%20Taurine%20%281.5%25%2C%20w%5C%2Fv%2C%20in%20drinking%20water%29%20administration%20and%20the%20HM%20diet%20for%206%20mo%20was%20found%20to%20decrease%20serum%20alanine%20transaminase%20and%20aspartate%20transaminase%20activities%2C%20hepatic%20lipid%20peroxide%20levels%2C%20and%20nitrotyrosine%20formation%20without%20any%20change%20in%20serum%20homocysteine%20levels.%20Decreases%20in%20Bax%20expression%2C%20increases%20in%20B-cell%20lymphoma-2%20expression%2C%20decreases%20in%20apoptotic%20cell%20number%2C%20and%20amelioration%20of%20histopathologic%20findings%20were%20observed%20in%20livers%20of%20rats%20fed%20with%20the%20taurine%20plus%20HM%20diet.%5CnCONCLUSION%3A%20Our%20results%20indicate%20that%20taurine%20has%20protective%20effects%20on%20hyperhomocysteinemia-induced%20toxicity%20by%20decreasing%20oxidative%20and%20nitrosative%20stresses%2C%20apoptosis%2C%20and%20necrosis%20in%20the%20liver.%22%2C%22date%22%3A%22Apr%202009%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.nut.2008.09.017%22%2C%22ISSN%22%3A%220899-9007%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-02-10T13%3A16%3A16Z%22%7D%7D%2C%7B%22key%22%3A%225TWH4ECZ%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Garlick%22%2C%22parsedDate%22%3A%222004%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EGarlick%20PJ.%20The%20nature%20of%20human%20hazards%20associated%20with%20excessive%20intake%20of%20amino%20acids.%20J%20Nutr.%202004%3B134%286%20Suppl%29%3A1633S-1639S%3B%20discussion%201664S-1666S%2C%201667S-1672S.%3C%5C%2Fdiv%3E%5Cn%20%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22The%20nature%20of%20human%20hazards%20associated%20with%20excessive%20intake%20of%20amino%20acids%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Peter%20J.%22%2C%22lastName%22%3A%22Garlick%22%7D%5D%2C%22abstractNote%22%3A%22In%20recent%20years%20there%20has%20been%20a%20large%20increase%20in%20the%20consumption%20of%20individual%20amino%20acids%20as%20dietary%20supplements.%20This%20has%20resulted%20not%20only%20from%20the%20use%20of%20certain%20amino%20acids%20as%20flavoring%20agents%2C%20but%20other%20amino%20acids%20are%20taken%20for%20perceived%20health%20benefit%2C%20for%20enhancement%20of%20physical%20performance%2C%20as%20well%20as%20for%20psychological%20effects.%20Two%20reviews%20of%20the%20scientific%20literature%20exist%20that%20mainly%20deal%20with%20effects%20in%20animals%2C%20and%20three%20major%20reports%20consider%20the%20safety%20of%20amino%20acids%20for%20human%20consumption.%20This%20article%20is%20a%20brief%20summary%20of%20the%20available%20evidence%20regarding%20the%20safety%20of%20individual%20amino%20acids%20when%20taken%20in%20excess%20relative%20to%20the%20amounts%20absorbed%20from%20dietary%20protein.%22%2C%22date%22%3A%2206%202004%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1093%5C%2Fjn%5C%2F134.6.1633S%22%2C%22ISSN%22%3A%220022-3166%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-02-10T13%3A15%3A54Z%22%7D%7D%2C%7B%22key%22%3A%22VMW3VIWE%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Sugiyama%20et%20al.%22%2C%22parsedDate%22%3A%221987-06%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3ESugiyama%20K%2C%20Kushima%20Y%2C%20Muramatsu%20K.%20Effect%20of%20dietary%20glycine%20on%20methionine%20metabolism%20in%20rats%20fed%20a%20high-methionine%20diet.%20J%20Nutr%20Sci%20Vitaminol.%201987%20Jun%3B33%283%29%3A195%26%23x2013%3B205.%3C%5C%2Fdiv%3E%5Cn%20%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Effect%20of%20dietary%20glycine%20on%20methionine%20metabolism%20in%20rats%20fed%20a%20high-methionine%20diet%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%22%2C%22lastName%22%3A%22Sugiyama%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%22%2C%22lastName%22%3A%22Kushima%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%22%2C%22lastName%22%3A%22Muramatsu%22%7D%5D%2C%22abstractNote%22%3A%22The%20alleviation%20mechanism%20of%20methionine%20toxicity%20by%20dietary%20glycine%20was%20investigated%20in%20weanling%20rats%20fed%20a%20high-methionine%20diet.%20When%20rats%20were%20fed%20a%2010%25%20casein%20diet%20containing%202%25%20methionine%2C%20the%20activities%20of%20methionine%20adenosyltransferase%2C%20cystathionine%20beta-synthase%2C%20and%20cystathionine%20gamma-lyase%2C%20which%20participate%20in%20the%20methionine%20metabolism%20in%20the%20transsulfuration%20pathway%2C%20were%20significantly%20enhanced.%20But%20the%20addition%20of%202%25%20glycine%20to%20the%20high%20methionine%20diet%20did%20not%20cause%20further%20increase%20in%20these%20enzyme%20activities%3B%20the%20activities%20of%20methionine%20adenosyltransferase%20and%20cystathionine%20beta-synthase%20were%20rather%20decreased%20while%20cystathionine%20gamma-lyase%20activity%20was%20not%20altered.%20Methionine%20transaminase%20activity%20was%20essentially%20insensitive%20to%20the%20dietary%20addition%20of%20methionine%20and%20glycine.%20In%20rats%20fed%20a%20high%20methionine%20diet%2C%20the%20hepatic%20methionine%20level%20was%20significantly%20increased%20with%20a%20concomitant%20decrease%20in%20the%20levels%20of%20glycine%2C%20serine%2C%20and%20threonine.%20The%20addition%20of%20glycine%20to%20the%20high%20methionine%20diet%20effectively%20suppressed%20the%20enhancement%20of%20the%20hepatic%20methionine%20level%20and%20almost%20completely%20restored%20the%20glycine%20level%2C%20but%20it%20only%20partially%20restored%20the%20serine%20level%20and%20further%20decreased%20the%20threonine%20level.%20From%20these%20results%2C%20it%20is%20suggested%20that%20the%20alleviating%20effect%20of%20dietary%20glycine%20on%20methionine%20toxicity%20is%20primarily%20elicited%20by%20the%20restoration%20of%20the%20hepatic%20glycine%20level%20rather%20than%20by%20an%20increase%20in%20hepatic%20enzyme%20activity.%22%2C%22date%22%3A%22Jun%201987%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.3177%5C%2Fjnsv.33.195%22%2C%22ISSN%22%3A%220301-4800%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-02-10T13%3A15%3A29Z%22%7D%7D%2C%7B%22key%22%3A%226B34JG2W%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Garlick%22%2C%22parsedDate%22%3A%222006%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EGarlick%20PJ.%20Toxicity%20of%20methionine%20in%20humans.%20J%20Nutr.%202006%3B136%286%20Suppl%29%3A1722S-1725S.%3C%5C%2Fdiv%3E%5Cn%20%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Toxicity%20of%20methionine%20in%20humans%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Peter%20J.%22%2C%22lastName%22%3A%22Garlick%22%7D%5D%2C%22abstractNote%22%3A%22The%20literature%20has%20been%20searched%20to%20identify%20evidence%20relating%20to%20the%20possible%20toxicity%20of%20the%20amino%20acid%20methionine%20in%20human%20subjects.%20Nutritional%20and%20metabolic%20studies%20have%20employed%20amounts%20of%20methionine%2C%20including%20the%20d%20and%20dl%20isomers%2C%20both%20below%20and%20above%20the%20requirement%20and%20have%20not%20reported%20adverse%20effects%20in%20adults%20and%20children.%20Although%20methionine%20is%20known%20to%20exacerbate%20psychopathological%20symptoms%20in%20schizophrenic%20patients%2C%20there%20is%20no%20evidence%20of%20similar%20effects%20in%20healthy%20subjects.%20The%20role%20of%20methionine%20as%20a%20precursor%20of%20homocysteine%20is%20the%20most%20notable%20cause%20for%20concern.%20A%20%5C%22loading%20dose%5C%22%20of%20methionine%20%280.1%20g%5C%2Fkg%29%20has%20been%20given%2C%20and%20the%20resultant%20acute%20increase%20in%20plasma%20homocysteine%20has%20been%20used%20as%20an%20index%20of%20the%20susceptibility%20to%20cardiovascular%20disease.%20Although%20this%20procedure%20results%20in%20vascular%20dysfunction%2C%20this%20is%20acute%20and%20unlikely%20to%20result%20in%20permanent%20damage.%20However%2C%20a%2010-fold%20larger%20dose%2C%20given%20mistakenly%2C%20resulted%20in%20death.%20Longer-term%20studies%20in%20adults%20have%20indicated%20no%20adverse%20consequences%20of%20moderate%20fluctuations%20in%20dietary%20methionine%20intake%2C%20but%20intakes%20higher%20than%205%20times%20normal%20resulted%20in%20elevated%20homocysteine%20levels.%20These%20effects%20of%20methionine%20on%20homocysteine%20and%20vascular%20function%20are%20moderated%20by%20supplements%20of%20vitamins%20B-6%2C%20B-12%2C%20C%2C%20and%20folic%20acid.%20In%20infants%2C%20methionine%20intakes%20of%202-5%20times%20normal%20resulted%20in%20impaired%20growth%20and%20extremely%20high%20plasma%20methionine%20levels%2C%20but%20no%20adverse%20long-term%20consequences%20were%20observed.%22%2C%22date%22%3A%2206%202006%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1093%5C%2Fjn%5C%2F136.6.1722S%22%2C%22ISSN%22%3A%220022-3166%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-02-10T13%3A15%3A13Z%22%7D%7D%2C%7B%22key%22%3A%229U3M3M6G%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Dilger%20and%20Baker%22%2C%22parsedDate%22%3A%222008-09%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EDilger%20RN%2C%20Baker%20DH.%20Excess%20dietary%20L-cysteine%20causes%20lethal%20metabolic%20acidosis%20in%20chicks.%20J%20Nutr.%202008%20Sep%3B138%289%29%3A1628%26%23x2013%3B33.%3C%5C%2Fdiv%3E%5Cn%20%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Excess%20dietary%20L-cysteine%20causes%20lethal%20metabolic%20acidosis%20in%20chicks%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ryan%20N.%22%2C%22lastName%22%3A%22Dilger%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%20H.%22%2C%22lastName%22%3A%22Baker%22%7D%5D%2C%22abstractNote%22%3A%22A%2072-h%20time-course%20study%20was%20conducted%20to%20elucidate%20the%20physiological%20mechanism%20underlying%20cysteine%20%28Cys%29%20toxicity%20in%20chicks%20beginning%20at%208-d%20posthatch.%20Biochemical%20markers%20quantified%20in%20plasma%20and%20liver%20samples%20collected%20from%20chicks%20receiving%2030%20g%5C%2Fkg%20excess%20dietary%20Cys%20were%20compared%20with%20baseline%20measurements%20from%20chicks%20receiving%20an%20unsupplemented%20corn-soybean%20meal%20diet%20over%20a%2072-h%20feeding%20period.%20Concomitant%20with%20chick%20mortality%20were%20indices%20of%20acute%20metabolic%20acidosis%2C%20including%20a%20rapid%20increase%20%28P%20%3C%200.001%29%20in%20anion%20gap%20that%20resulted%20from%20a%20reduction%20%28P%20%3C%200.001%29%20in%20plasma%20HCO%283%29%28-%29%20of%20approximately%2040%25%20and%20a%202.8-fold%20increase%20%28P%20%3C%200.001%29%20in%20plasma%20sulfate%20in%20chicks%20receiving%20excess%20Cys.%20Additionally%2C%20provision%20of%2030%20g%5C%2Fkg%20excess%20Cys%20resulted%20in%20a%201.5-fold%20increase%20%28P%20%3C%200.05%29%20in%20hepatic%20oxidized%20glutathione%20compared%20with%20the%200-h%20control%20time-point.%20Excess%20dietary%20Cys%20did%20not%20affect%20plasma%20free%20Met%2C%20but%20plasma%20free%20Cys%20increased%20%28P%20%3C%200.05%29%20from%2089%20to%20107%20mumol%5C%2FL%20at%2012%20h%20and%20remained%20elevated%20through%2036%20h.%20Strikingly%2C%20ingestion%20of%2030%20g%5C%2Fkg%20excess%20Cys%20caused%20more%20than%20a%20doubling%20%28P%20%3C%200.001%29%20of%20plasma%20free%20cystine%2C%20the%20oxidized%20form%20of%20Cys%2C%20beginning%2012%20h%20after%20initiating%20the%20study%2C%20and%20it%20remained%20elevated%20throughout%20the%2072-h%20feeding%20period.%20Taken%20together%2C%20these%20data%20suggest%20that%20ingestion%20of%2030%20g%5C%2Fkg%20excess%20l-Cys%20causes%20both%20acute%20metabolic%20acidosis%20and%20oxidative%20stress%20in%20young%20chicks%20when%20fed%20a%20nutritionally%20adequate%2C%20corn-soybean%20meal%20diet.%22%2C%22date%22%3A%22Sep%202008%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1093%5C%2Fjn%5C%2F138.9.1628%22%2C%22ISSN%22%3A%221541-6100%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-02-10T13%3A05%3A48Z%22%7D%7D%2C%7B%22key%22%3A%22EREIA47L%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Benevenga%20and%20Steele%22%2C%22parsedDate%22%3A%221984%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EBenevenga%20NJ%2C%20Steele%20RD.%20Adverse%20effects%20of%20excessive%20consumption%20of%20amino%20acids.%20Annu%20Rev%20Nutr.%201984%3B4%3A157%26%23x2013%3B81.%3C%5C%2Fdiv%3E%5Cn%20%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Adverse%20effects%20of%20excessive%20consumption%20of%20amino%20acids%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22N.%20J.%22%2C%22lastName%22%3A%22Benevenga%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%20D.%22%2C%22lastName%22%3A%22Steele%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%221984%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1146%5C%2Fannurev.nu.04.070184.001105%22%2C%22ISSN%22%3A%220199-9885%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222020-02-10T13%3A05%3A27Z%22%7D%7D%2C%7B%22key%22%3A%22H69WIWP8%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Chaturvedi%20et%20al.%22%2C%22parsedDate%22%3A%222018-08-01%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EChaturvedi%20S%2C%20Hoffman%20RM%2C%20Bertino%20JR.%20Exploiting%20methionine%20restriction%20for%20cancer%20treatment.%20Biochemical%20Pharmacology%20%5BInternet%5D.%202018%20Aug%201%20%5Bcited%202019%20Aug%203%5D%3B154%3A170%26%23x2013%3B3.%20Available%20from%3A%20%3Ca%20href%3D%27http%3A%5C%2F%5C%2Fwww.sciencedirect.com%5C%2Fscience%5C%2Farticle%5C%2Fpii%5C%2FS0006295218301886%27%3Ehttp%3A%5C%2F%5C%2Fwww.sciencedirect.com%5C%2Fscience%5C%2Farticle%5C%2Fpii%5C%2FS0006295218301886%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Exploiting%20methionine%20restriction%20for%20cancer%20treatment%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sushma%22%2C%22lastName%22%3A%22Chaturvedi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Robert%20M.%22%2C%22lastName%22%3A%22Hoffman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Joseph%20R.%22%2C%22lastName%22%3A%22Bertino%22%7D%5D%2C%22abstractNote%22%3A%22Normal%20cells%20can%20synthesize%20sufficient%20methionine%20for%20growth%20requirements%20from%20homocysteine%20and%205-methyltetrahydrofolate%20and%20vitamin%20B12.%20However%2C%20many%20cancer-cell%20types%20require%20exogenous%20methionine%20for%20survival%20and%20therefore%20methionine%20restriction%20is%20a%20promising%20avenue%20for%20treatment.%20While%20the%20lack%20of%20the%20methionine%20salvage%20enzyme%20methylthioadenosine%20phosphorylase%20%28MTAP%29%20deficiency%20is%20associated%20with%20methionine%20dependence%20in%20cancer%20cells%2C%20there%20are%20other%20causes%20for%20tumors%20to%20require%20exogenous%20methionine.%20In%20this%20review%20we%20describe%20studies%20that%20show%20restricting%20methionine%20to%20certain%20cancers%20by%20diet%20or%20by%20enzyme%20depletion%2C%20alone%20or%20in%20combination%20with%20certain%20chemotherapeutics%20is%20a%20promising%20antitumor%20strategy.%20The%20basis%20for%20methionine%20dependence%20in%20tumor%20cells%20is%20also%20briefly%20reviewed.%22%2C%22date%22%3A%22August%201%2C%202018%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.bcp.2018.05.003%22%2C%22ISSN%22%3A%220006-2952%22%2C%22url%22%3A%22http%3A%5C%2F%5C%2Fwww.sciencedirect.com%5C%2Fscience%5C%2Farticle%5C%2Fpii%5C%2FS0006295218301886%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222019-08-03T09%3A53%3A53Z%22%7D%7D%2C%7B%22key%22%3A%22TWHEU3I3%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Gao%20et%20al.%22%2C%22parsedDate%22%3A%222019-07-31%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EGao%20X%2C%20Sanderson%20SM%2C%20Dai%20Z%2C%20Reid%20MA%2C%20Cooper%20DE%2C%20Lu%20M%2C%20et%20al.%20Dietary%20methionine%20influences%20therapy%20in%20mouse%20cancer%20models%20and%20alters%20human%20metabolism.%20Nature%20%5BInternet%5D.%202019%20Jul%2031%20%5Bcited%202019%20Aug%201%5D%3B1.%20Available%20from%3A%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41586-019-1437-3%27%3Ehttps%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41586-019-1437-3%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Dietary%20methionine%20influences%20therapy%20in%20mouse%20cancer%20models%20and%20alters%20human%20metabolism%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xia%22%2C%22lastName%22%3A%22Gao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sydney%20M.%22%2C%22lastName%22%3A%22Sanderson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ziwei%22%2C%22lastName%22%3A%22Dai%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%20A.%22%2C%22lastName%22%3A%22Reid%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniel%20E.%22%2C%22lastName%22%3A%22Cooper%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Min%22%2C%22lastName%22%3A%22Lu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22John%20P.%22%2C%22lastName%22%3A%22Richie%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Amy%22%2C%22lastName%22%3A%22Ciccarella%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ana%22%2C%22lastName%22%3A%22Calcagnotto%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Peter%20G.%22%2C%22lastName%22%3A%22Mikhael%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Samantha%20J.%22%2C%22lastName%22%3A%22Mentch%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Juan%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gene%22%2C%22lastName%22%3A%22Ables%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%20G.%22%2C%22lastName%22%3A%22Kirsch%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%20S.%22%2C%22lastName%22%3A%22Hsu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sailendra%20N.%22%2C%22lastName%22%3A%22Nichenametla%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jason%20W.%22%2C%22lastName%22%3A%22Locasale%22%7D%5D%2C%22abstractNote%22%3A%22In%20two%20patient-derived%20xenograft%20models%20of%20colorectal%20cancer%20and%20a%20mouse%20model%20of%20autochthonous%20soft-tissue%20sarcoma%2C%20dietary%20restriction%20of%20methionine%20influences%20the%20outcome%20of%20cancer%20and%20interacts%20with%20antimetabolite%20and%20radiation%20therapies%2C%20through%20effects%20on%20one-carbon%20metabolism.%22%2C%22date%22%3A%222019-07-31%22%2C%22language%22%3A%22En%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41586-019-1437-3%22%2C%22ISSN%22%3A%221476-4687%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41586-019-1437-3%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222019-08-01T09%3A20%3A53Z%22%7D%7D%2C%7B%22key%22%3A%2255FXT2Y8%22%2C%22library%22%3A%7B%22id%22%3A1793304%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Dong%20Zhen%20et%20al.%22%2C%22parsedDate%22%3A%222018-02-05%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%20%20%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EDong%20Zhen%2C%20Sinha%20Raghu%2C%20Richie%20John%20P.%20Disease%20prevention%20and%20delayed%20aging%20by%20dietary%20sulfur%20amino%20acid%20restriction%3A%20translational%20implications.%20Annals%20of%20the%20New%20York%20Academy%20of%20Sciences%20%5BInternet%5D.%202018%20Feb%205%20%5Bcited%202018%20Apr%206%5D%3B0%280%29.%20Available%20from%3A%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fnyaspubs.onlinelibrary.wiley.com%5C%2Fdoi%5C%2Fabs%5C%2F10.1111%5C%2Fnyas.13584%27%3Ehttps%3A%5C%2F%5C%2Fnyaspubs.onlinelibrary.wiley.com%5C%2Fdoi%5C%2Fabs%5C%2F10.1111%5C%2Fnyas.13584%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%20%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Disease%20prevention%20and%20delayed%20aging%20by%20dietary%20sulfur%20amino%20acid%20restriction%3A%20translational%20implications%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Dong%20Zhen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Sinha%20Raghu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Richie%20John%20P.%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20Sulfur%20amino%20acids%20%28SAAs%29%20play%20numerous%20critical%20roles%20in%20metabolism%20and%20overall%20health%20maintenance.%20Preclinical%20studies%20have%20demonstrated%20that%20SAA%3Frestricted%20diets%20have%20many%20beneficial%20effects%2C%20including%20extending%20life%20span%20and%20preventing%20the%20development%20of%20a%20variety%20of%20diseases.%20Dietary%20sulfur%20amino%20acid%20restriction%20%28SAAR%29%20is%20characterized%20by%20chronic%20restrictions%20of%20methionine%20and%20cysteine%20but%20not%20calories%20and%20is%20associated%20with%20reductions%20in%20body%20weight%2C%20adiposity%20and%20oxidative%20stress%2C%20and%20metabolic%20changes%20in%20adipose%20tissue%20and%20liver%20resulting%20in%20enhanced%20insulin%20sensitivity%20and%20energy%20expenditure.%20SAAR%3Finduced%20changes%20in%20blood%20biomarkers%20include%20reductions%20in%20insulin%2C%20insulin%3Flike%20growth%20factor%3F1%2C%20glucose%2C%20and%20leptin%20and%20increases%20in%20adiponectin%20and%20fibroblast%20growth%20factor%2021.%20On%20the%20basis%20of%20these%20preclinical%20data%2C%20SAAR%20may%20also%20have%20similar%20benefits%20in%20humans.%20While%20little%20is%20known%20of%20the%20translational%20significance%20of%20SAAR%2C%20its%20potential%20feasibility%20in%20humans%20is%20supported%20by%20findings%20of%20its%20effectiveness%20in%20rodents%2C%20even%20when%20initiated%20in%20adult%20animals.%20To%20date%2C%20there%20have%20been%20no%20controlled%20feeding%20studies%20of%20SAAR%20in%20humans%3B%20however%2C%20there%20have%20been%20numerous%20relevant%20epidemiologic%20and%20disease%3Fbased%20clinical%20investigations%20reported.%20Here%2C%20we%20summarize%20observations%20from%20these%20clinical%20investigations%20to%20provide%20insight%20into%20the%20potential%20effectiveness%20of%20SAAR%20for%20humans.%22%2C%22date%22%3A%22February%205%2C%202018%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1111%5C%2Fnyas.13584%22%2C%22ISSN%22%3A%220077-8923%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fnyaspubs.onlinelibrary.wiley.com%5C%2Fdoi%5C%2Fabs%5C%2F10.1111%5C%2Fnyas.13584%22%2C%22collections%22%3A%5B%22UCGUH2EM%22%5D%2C%22dateModified%22%3A%222018-04-06T15%3A51%3A42Z%22%7D%7D%5D%7D
1.
Ables GP, Perrone CE, Orentreich D, Orentreich N. Methionine-restricted C57BL/6J mice are resistant to diet-induced obesity and insulin resistance but have low bone density. PLoS ONE. 2012;7(12):e51357.
1.
Malloy VL, Perrone CE, Mattocks DAL, Ables GP, Caliendo NS, Orentreich DS, et al. Methionine restriction prevents the progression of hepatic steatosis in leptin-deficient obese mice. Metab Clin Exp. 2013 Nov;62(11):1651–61.
1.
Lee BC, Kaya A, Ma S, Kim G, Gerashchenko MV, Yim SH, et al. Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino acid status. Nat Commun [Internet]. 2014 Apr 7 [cited 2020 Apr 27];5:3592. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350766/
1.
Malloy VL, Krajcik RA, Bailey SJ, Hristopoulos G, Plummer JD, Orentreich N. Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer 344 rats independent of energy restriction. Aging Cell. 2006 Aug;5(4):305–14.
1.
Perrone CE, Malloy VL, Orentreich DS, Orentreich N. Metabolic adaptations to methionine restriction that benefit health and lifespan in rodents. Exp Gerontol. 2013 Jul;48(7):654–60.
1.
Orentreich N, Matias JR, DeFelice A, Zimmerman JA. Low methionine ingestion by rats extends life span. J Nutr. 1993 Feb;123(2):269–74.
1.
Miller RA, Buehner G, Chang Y, Harper JM, Sigler R, Smith-Wheelock M. Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell. 2005 Jun;4(3):119–25.
1.
Cavuoto P, Fenech MF. A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension. Cancer Treat Rev. 2012 Oct;38(6):726–36.
1.
Yalçinkaya S, Unlüçerçi Y, Giriş M, Olgaç V, Doğru-Abbasoğlu S, Uysal M. Oxidative and nitrosative stress and apoptosis in the liver of rats fed on high methionine diet: protective effect of taurine. Nutrition. 2009 Apr;25(4):436–44.
1.
Garlick PJ. The nature of human hazards associated with excessive intake of amino acids. J Nutr. 2004;134(6 Suppl):1633S-1639S; discussion 1664S-1666S, 1667S-1672S.
1.
Sugiyama K, Kushima Y, Muramatsu K. Effect of dietary glycine on methionine metabolism in rats fed a high-methionine diet. J Nutr Sci Vitaminol. 1987 Jun;33(3):195–205.
1.
Garlick PJ. Toxicity of methionine in humans. J Nutr. 2006;136(6 Suppl):1722S-1725S.
1.
Dilger RN, Baker DH. Excess dietary L-cysteine causes lethal metabolic acidosis in chicks. J Nutr. 2008 Sep;138(9):1628–33.
1.
Benevenga NJ, Steele RD. Adverse effects of excessive consumption of amino acids. Annu Rev Nutr. 1984;4:157–81.
1.
Gao X, Sanderson SM, Dai Z, Reid MA, Cooper DE, Lu M, et al. Dietary methionine influences therapy in mouse cancer models and alters human metabolism. Nature [Internet]. 2019 Jul 31 [cited 2019 Aug 1];1. Available from:
https://www.nature.com/articles/s41586-019-1437-3
Deixe o seu comentário