Advances in Clinical and Experimental Medicine

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Advances in Clinical and Experimental Medicine

2010, vol. 19, nr 2, March-April, p. 233–243

Publication type: review article

Language: English

Asymmetric Dimethylarginine Synthesis and Degradation Under Physiological and Pathological Conditions

Asymetryczna dimetyloarginina – synteza i rozkład w warunkach fizjologicznych i patologicznych

Małgorzata Trocha1,, Anna Merwid-Ląd1,, Andrzej Szuba2,, Tomasz Sozański1,, Jan Magdalan1,, Adam Szeląg1,

1 Department of Pharmacology Wroclaw Medical University, Poland

2 Department of Internal Medicine, Occupational Diseases, and Hypertension, Wroclaw Medical University, Poland

Abstract

Asymmetric dimethylarginine (ADMA) is an endogenous methylated amino acid derived from arginine. ADMA can inhibit the activity of all isoforms of nitric oxide synthase (NOS). Protein arginine methyltransferases (PRMTs) catalyze the synthesis of ADMA and dimethylarginine dimethylaminohydrolase (DDAH) is responsible for the metabolism of this compound. ADMA enters cells through cationic amino-acid transporters (CATs), which are known to be y+ carriers. Many factors can regulate the synthesis, transport, metabolism, or excretion of ADMA. In various pathological states such as hypercholesterolemia, hyperglycemia, hyperhomocysteinemia, hypertension, coronary artery disease, heart failure, and stroke, plasma levels of ADMA may increase twoor even tenfold, contributing to inhibition of NO synthesis and endothelial dysfunction. Impaired liver or renal function could also have an impact on the plasma concentration of ADMA. In some situations such as neurological disorders, decreased levels of ADMA are noted. It is very important to discover which states or drugs can increase or decrease the level of ADMA and what the mechanism of that action is.

Streszczenie

Asymetryczna dimetyloarginina (ADMA) to endogenny aminokwas powstający z argininy. ADMA hamuje aktywność wszystkich izoform syntetaz tlenku azotu (NOS). Metylotransferazy argininowe (PRMTs) katalizują syntezę ADMA, a dimetyloaminohydrolaza dimetyloargininy (DDAH) odpowiada za rozkład tego związku. Kationowe transportery aminokwasów (CATs) znane, jako y+ transportery pozwalają na gromadzenie się ADMA we wnętrzu komórki. Wiele czynników wpływa na syntezę, transport, metabolizm i wydalanie ADMA z organizmu. Wśród chorób należy wymienić hipercholesterolemię, hiperglikemię, hiperhomocysteinemię, chorobę wieńcową, niewydolność serca i udar. Wszystkim tym stanom towarzyszy 2-, a nawet 4-krotny wzrost stężenia ADMA we krwi, zahamowanie syntezy NO i dysfunkcja śródbłonka. Upośledzona czynność wątroby i nerek, narządów odpowiedzialnych za wydalanie ADMA, również wpływa na wzrost stężenia tego związku w organizmie. W niektórych stanach, np. w chorobach neurologicznych, stężenie ADMA jest zmniejszone. Jest bardzo ważne, aby poznać, które choroby lub substancje są odpowiedzialne za zwiększone lub zmniejszone stężenie ADMA oraz jaki jest mechanizm tego zjawiska.

Key words

ADMA, PRMTs, DDAH

Słowa kluczowe

ADMA, PRMTs, DDAH

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