Proximal Tubule Cell Hypothesis for Cardiorenal Syndrome in Diabetes
Figure 3
Intracellular synthesis and metabolism of homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) and their biochemical link. Vitamin B12 serves as a cofactor for the formation of methionine (Met) from homocysteine (Hcy) by methionine synthase using 5-methyl-tetrahydrofolate (5-MTHF), the dominant folate form in serum. S-adenosylmethionine (AdoMet) is the intermediate in this reaction and serves as the methyl donor to form S-adenosylhomocysteine (AdoHcy). Hcy is either remethylated to Met or transsulfurated to cysteine. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of endothelial nitric oxide synthase (eNOS). ADMA is formed by methylation of arginine residues in proteins with protein methyltransferase (PRMT) and released after proteolysis. Metabolism of ADMA is mediated by dimethylarginine dimethylaminohydrolases (DDAHs), which are downregulated by reactive oxygen species and Hcy.
