L-Arginine/NO Pathway Is Altered in Children with Haemolytic-Uraemic Syndrome (HUS)

Figure 7

Proposal of the status of the L-arginine/NO pathway in the haemolytic-uraemic syndrome (HUS) in childhood. The enzyme NOS converts L-arginine into L-citrulline (not shown) and NO which plays multiple physiological roles. NO autooxidizes to nitrite. In red blood cells, NO is oxidized to nitrate. Nitrite and nitrate are excreted in the urine. By far the major part of L-arginine participates in the urea cycle and is utilized in protein synthesis. PRMT methylate L-arginine in proteins and methylated proteins are hydrolyzed to the soluble L-arginine derivates SDMA, LMMA, and ADMA. LMMA and ADMA act as inhibitors of NOS, thus controlling NO synthesis. ADMA is hydrolyzed by DDAH to L-citrulline (not shown) and DMA which is excreted in the urine. The status of the L-arginine/NO pathway can be described satisfactorily by measuring nitrite, nitrate, ADMA, L-arginine, and DMA in plasma or serum and urine. In HUS, NO and ADMA biosynthesis is diminished, whereas DDAH activity is not altered. Oxidative stress is elevated, haemolysis is increased, which releases Hb that in turn elevates oxidative stress, thus finally establishing a vicious circle. Minus means diminished; plus means increased. Abbreviations used in this Figure: ADMA: asymmetric dimethylarginine; DDAH: dimethylarginine dimethylaminohydrolase; DMA: dimethylamine; LMMA: monomethyl arginine; NOS: nitric oxide synthase; PRMT: protein arginine methyl transferase; SDMA: symmetric dimethylarginine.