Sandbox Reserved 1058: Difference between revisions

Dimethylarginine Dimethyaminohydrolase (commonly known as DDAH) is a member of the <span class="plainlinks">[https://en.wikipedia.org/wiki/Hydrolase hydrolase]</span> family of enzymes which use water to break down molecules <ref name="palm">Palm F, Onozato ML, Luo Z, Wilcox CS. Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems. American Journal of Physiology. 2007 Dec 1;293(6):3227-3245. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/17933965 17933965]</span> doi:<span class="plainlinks">[http://ajpheart.physiology.org/content/293/6/H3227 10.1152/ajpheart.00998.2007]</span></ref>. Specifically, DDAH is a <span class="plainlinks">[https://en.wikipedia.org/wiki/Nitric_oxide_synthase nitric oxide synthase (NOS)]</span> regulator. Its metabolizes free arginine derivatives, namely <span class="plainlinks">[https://en.wikipedia.org/wiki/Asymmetric_dimethylarginine NѠ,NѠ-dimethyl-L-arginine (ADMA)]</span> and <span class="plainlinks">[https://en.wikipedia.org/wiki/Methylarginine NѠ-methyl-L-arginine (MMA)]</span> which competitively inhibit NOS <ref name="tran">Tran CTL, Leiper JM, Vallance P. The DDAH/ADMA/NOS pathway. Atherosclerosis Supplements. 2003 Dec;4(4):33-40. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/14664901 14664901]</span> doi:<span class="plainlinks">[http://www.sciencedirect.com/science/article/pii/S1567568803000321 10.1016/S1567-5688(03)00032-1]</span></ref>. DDAH converts MMA and ADMA to <span class="plainlinks">[https://en.wikipedia.org/wiki/Citrulline L-citrulline]</span> and monoamine or dimethylamine <ref name="frey">Frey D, Braun O, Briand C, Vasak M, Grutter MG. Structure of the mammalian NOS regulator dimethylarginine dimethylaminohydrolase: a basis for the design of specific inhibitors. Structure. 2006 May;14(5):901-911. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/16698551 16698551]</span> doi:<span class="plainlinks">[http://www.sciencedirect.com/science/article/pii/S0969212606001717 10.1016/j.str.2006.03.006]</span></ref>. DDAH is expressed in the cytosol of cells in humans, mice, rates, sheep, cattle, and bacteria <ref name="palm" />. DDAH activity has been localized mainly to the brain, kidney, pancreas, and liver in these organisms. If DDAH is overexpressed, NOS can be activated <ref name="frey" />. ADMA and MMA can <span class="plainlinks">[https://en.wikipedia.org/wiki/Enzyme_inhibitor inhibit]</span> the synthesis of NO by competitively inhibiting all three kinds of <span class="plainlinks">[https://en.wikipedia.org/wiki/Nitric_oxide_synthase NOS (endothelial, neuronal, and inducible)]</span> <ref name="frey" />. Underexpression or inhibition of DDAH decreases NOS activity and NO levels will decrease. Because of <span class="plainlinks">[https://en.wikipedia.org/wiki/Nitric_oxide nitric oxide’s (NO)]</span> role in signaling and defense, NO levels in an organism must be regulated to reduce damage to cells <ref name="janssen">Janssen W, Pullamsetti SS, Cooke J, Weissmann N, Guenther A, Schermuly RT. The role of dimethylarginine dimethylaminohydrolase (DDAH) in pulmonary fibrosis. The Journal of Pathology. 2012 Dec 12;229(2):242-249. Epub 2013 Jan. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/23097221 23097221]</span> doi:<span class="plainlinks">[http://onlinelibrary.wiley.com/doi/10.1002/path.4127/references;jsessionid=C34C6C633A21C2ECE14278BBC902AD71.f03t04?globalMessage=0 10.1002/path.4127]</span></ref>. NO is made by NOS creating L-citrulline from <span class="plainlinks">[https://en.wikipedia.org/wiki/Arginine L-arginine]</span> <ref name="frey" />. In humans, many diseases can come from improper control of NO levels including <span class="plainlinks">[https://en.wikipedia.org/wiki/Diabetes_mellitus diabetes mellitus]</span> and <span class="plainlinks">[http://www.mayoclinic.org/diseases-conditions/high-blood-pressure/basics/definition/con-20019580 hypertension]</span>. Current research has identified several inhibitors of DDAH which could be important in fighting diseases involving irregular NO levels <ref name="frey" />.