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.[1]
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.[2][3][4]
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.
Protein detoxification pathway.
^Ito, A. Novel Mechanism for Endothelial Dysfunction: Dysregulation of Dimethylarginine Dimethylaminohydrolase Circulation 1999;99;3092-3095
^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? Archived 2011-07-13 at the Wayback Machine Am J Kidney Dis. 2005;46:186-202
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