User:Kaitlyn Enderle/Sandbox 1

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Function

Disease

Relevance

DDAH works to hydrolyze MMA and ADMA. Both MMA and ADMA competitively inhibit NO synthesis by inhibiting Nitric Oxide Synthase (NOS). Because NO is highly toxic, freely diffusible across membranes, and its radical form is fairly reactive, cells must maintain a large control on concentrations by regulating NOS activity and the activity of enzymes such as DDAH that have an indirect effect of the concentration of NO. An imbalance of NO contributes to several diseases. Low NO levels, potentially caused by low DDAH activity and therefore high MMA and ADMA concentrations, have been implicated with diseases such as uremia, chronic heart failure, atherosclerosis, and hyperhomocysteinemia. High levels of NO have been involved with diseases such as septic shock, migraine, inflammation, and neurodegenerative disorders. Because of the effects on NO levels and known inhibitors to DDAH, regulation of DDAH may be an effective way to regulate NO levels therefore treating the diseases.

Structural highlights

Inhibitors

Zinc at pH 6.3

Zinc at pH 9

L-Citrulline

L-Homocystine

Figure Legend

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