Creatinine inhibits D-amino acid oxidase.
Inhibition of D-amino acid oxidase (DAO) activity by various uremic retention products and guanidino compounds was investigated. Creatinine (CTN) was found to inhibit DAO at a similar concentration in the sera of uremic patients. The inhibition was competitive and the K(i) value was 2.7 mM. Moreover, CTN was shown to interact with flavin adenine dinucleotide (FAD), a coenzyme of DAO. The UV spectral change of FAD bound to DAO was observed in the visible region by addition of CTN. These findings suggest that the increase in serum and tissue CTN concentrations might be responsible, in part, for the increase in D-amino acids in the sera of uremic patients.
Nohara
Y
Y
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan. d96003@pharm.teikyo-u.ac.jp
Suzuki
J
J
Kinoshita
T
T
Watanabe
M
M
D000409:Alanine / Q000097:blood; D000410:Alanine Transaminase / Q000378:metabolism; D003404:Creatinine / Q000097:blood / Q000494:pharmacology*; D003605:D-Amino-Acid Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D012694:Serine / Q000097:blood; D014511:Uremia / Q000201:enzymology*
D005182:Flavin-Adenine Dinucleotide; D012694:Serine; D003404:Creatinine; D003605:D-Amino-Acid Oxidase; D000410:Alanine Transaminase; D000409:Alanine