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Metabolism of NG,NG-and NG,N'G-dimethylarginine in rats.

Abstract：

:The metabolic fates of NG,NG-and NG,N'G-dimethylarginines in rats were investigated isotopically and novel metabolites, alpha-keto-delta-(N,N-dimethylguanidino)-and alpha-keto-delta-(N,N'-dimethylguanidino)valeric acids and gamma-(N,N-dimethylguanidino)-and gamma-(N,N'-dimethylguanidino)butyric acids were identified. In the case of the rats injected with NG,NG-dimethyl-L-[1,2,3,4,5-14C]arginine, about 13% of the radioactivity was recovered in the first 12-h urine and was distributed in the following metabolites (relative ratios): unchanged NG,NG-dimethyl-L-arginine (35.2%), gamma-(N,N-dimethylguanidino)butyric acid (18.4%), alpha-keto-delta-(N,N-dimethylguanidino)valeric acid (16.4%), and N alpha-acetyl-NG,NG-dimethyl-L-arginine (8.5%). The radioactivity retained in the tissues was found mainly in citrulline and was further distributed in ornithine, arginine, and glutamic acid and even in protein-bound arginine. In the case of NG,N'G-dimethyl-L-[1,2,3,4,5-14C]arginine-injected rats, about 75% of the radioactivity was excreted in the first 12-h urine and was recovered in the following metabolites (relative ratios): N alpha-acetyl-NG,N'G-dimethyl-L-arginine (48.4%), unchanged NG,N'G-dimethyl-L-arginine (23.7%), alpha-keto-delta-(N,N'-dimethylguanidino)valeric acid (20.2%), and gamma-(N,N'-dimethylguanidino)butyric acid (9.6%). In the tissues, most of the radioactivity was associated with unchanged NG,N'G-dimethyl-L-arginine. These findings show that both dimethylarginines are metabolized by a pathway forming the corresponding alpha-ketoacid analogs and the oxidatively decarboxylated products of the alpha-ketoacids in addition to the N alpha-acetyl conjugates identified previously (K. Sasaoka, T. Ogawa, and M. Kimoto (1982) Arch. Biochem. Biophys. 219, 454-458), and NG,NG-dimethyl-L-arginine is catabolized by an additional pathway leading to the formation of citrulline and its metabolically related amino acids. By considering their catabolism, an attempt to use urinary dimethylarginines as an index of in vivo breakdown of tissue proteins is invalid at least in rats.

journal_name

Arch Biochem Biophys

journal_title

Archives of biochemistry and biophysics

authors

Ogawa T,Kimoto M,Watanabe H,Sasaoka K

doi

10.1016/0003-9861(87)90060-9

subject

Has Abstract

pub_date

1987-02-01 00:00:00

pages

526-37

issue

eissn

0003-9861

issn

1096-0384

pii

0003-9861(87)90060-9

journal_volume

252

pub_type

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Metabolism of NG,NG-and NG,N'G-dimethylarginine in rats.