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Protein detoxification is the process by which proteins containing methylated arginine are broken down and removed from the body. :Arginine (Arg) is a non-essential amino acid and one of the most commonly occurring natural amino acids. Methylated arginine is a modified version of arginine that is commonly formed from protein arginine (arginine incorporated in protein). Asymmetrically methylated forms of arginine are toxic when released during protein turnover. :The protein detoxification pathway eliminates free methylated-arginine derivatives from the cell. Symmetrically methylated forms are not toxic and are excreted unchanged by the kidney. Asymmetrically methylated forms however are toxic and must first be broken down. This step requires the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Impairment of DDAH function slows breakdown and increases the level of toxic asymmetrically methylated arginine forms.〔Ito, A. (Novel Mechanism for Endothelial Dysfunction: Dysregulation of Dimethylarginine Dimethylaminohydrolase ) Circulation 1999;99;3092-3095〕 :Long term exposure to these toxic amino acids is associated with endothelial dysfunction, arterial stiffness, insulin resistance, chronic kidney disease, heart disease, dementia and ageing.〔Boger, R. (The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor ) Cardiovascular Research 2003;59:824–833〕〔Palm, F. (Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems ) Am J Physiol Heart Circ Physiol 2007;293:H3227–H3245〕〔Kielstein, J. (Asymmetric Dimethylarginine: A Cardiovascular Risk Factor and a Uremic Toxin Coming of Age? ) Am J Kidney Dis. 2005;46:186-202〕 Therapeutic strategies that target the protein detoxification pathway aim to: : * reduce intracellular levels of free asymmetrically methylated arginine derivatives, : * slow the ageing process : * delay the development of disorders associated with ageing. ==History== In 1970, it was demonstrated that protein turnover releases the free methylated arginine derivatives: #asymmetric dimethylarginine (ADMA), #methylarginine, (also referred to as N-methyl-L-arginine, N-monomethylargine or L-NMMA), and #symmetrical dimethylarginine (SDMA).〔Kakimoto, Y. (Isolation and identification of N,N and N,N-Dimethyl-arginine, N-mono-, and Trimethyllysine, and Glucosylgalactosyl-, and Galactosyl-δ-hydroxylysine from human urine ) J Biol Chem 1970;245: 5751-5758〕 The potential toxicity of the two asymmetrically methylated amino acids however was not fully appreciated until 1992 when Patrick Vallance and his London co-workers at the Wellcome Research Laboratories demonstrated that ADMA inhibits nitric oxide synthase (NOS).〔Vallance, P. (Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure ) Lancet 1992;339(8793):572-5〕 Then, in 1996 MacAllister at St George's Hospital Medical School in London, recognised that inhibiting the enzyme DDAH increases intracellular concentrations of ADMA.〔MacAllister, R. (Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase ) Br J Pharmacol 1996;119(8):1533-40〕 To describe the process of protein turnover, the elimination of free methylated arginine derivatives and the catabolism of the two asymmetrically methylated arginine derivatives ADMA and L-NMMA, the Australian physician (Trevor Tingate ) coined the term ''protein detoxification'' in 2010. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Protein detoxification」の詳細全文を読む スポンサード リンク
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