Abstract
Asymmetric and symmetric dimethylarginine (ADMA and SDMA, respectively) are toxic, non-proteinogenic amino acids formed by post-translational modification and are uremic toxins that inhibit nitric oxide (NO) production and play multifunctional roles in many human diseases. Both ADMA and SDMA have emerged as strong predictors of cardiovascular events and death in a range of illnesses. Major progress has been made in research on ADMA-lowering therapies in animal studies; however, further studies are required to fill the translational gap between animal models and clinical trials in order to treat human diseases related to elevated ADMA/SDMA levels. Here, we review the reported impacts of ADMA and SDMA on human health and disease, focusing on the synthesis and metabolism of ADMA and SDMA; the pathophysiological roles of these dimethylarginines; clinical conditions and animal models associated with elevated ADMA and SDMA levels; and potential therapies against ADMA and SDMA. There is currently no specific pharmacological therapy for lowering the levels and counteracting the deleterious effects of ADMA and SDMA. A better understanding of the mechanisms underlying the impact of ADMA and SDMA on a wide range of human diseases is essential to the development of specific therapies against diseases related to ADMA and SDMA.
Highlights
The dimethylarginines, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), were first isolated from human urine in 1970 [1]
Since the first isolation of ADMA and SDMA from human urine in 1970, there has been substantial evidence revealing the significance of these two non-proteinogenic amino acids in human health and diseases
ADMA and SDMA are known uremic toxins and the most well-known effect of these two toxic amino acids is the suppression of nitric oxide (NO) production
Summary
The dimethylarginines, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), were first isolated from human urine in 1970 [1]. Among the guanidine compounds listed as uremic toxins [2], ADMA and SDMA and have been increasingly recognized as putative toxic non-proteinogenic amino acids in a wide range of human diseases over the past decades [3,4,5,6,7,8,9,10,11]. The biological relevance of ADMA as an endogenous inhibitor of nitric oxide synthase (NOS). Toxins 2017, 9, 92 evidence indicates that ADMA and SDMA are involved in the pathophysiology of endothelial dysfunction [13], atherosclerosis [4], oxidative stress [14,15], inflammation [16,17], uremia [8], apoptosis, [18], autophagy [19], and impaired immunological function [20]. This review provides an overview of potential pathophysiological roles for both ADMA and SDMA in human health and disease, with emphasis on the synthesis and metabolism of ADMA and SDMA, the pathophysiology of dimethylarginines, clinical conditions with elevated ADMA and SDMA concentrations, and potential therapies to reduce ADMA and SDMA levels
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