AMP deaminase 3 deficiency enhanced 5'-AMP induction of hypometabolism.
A hypometabolic state can be induced in mice by 5'-AMP administration. Previously we proposed that an underlying mechanism for this hypometabolism is linked to reduced erythrocyte oxygen transport function due to 5'-AMP uptake altering the cellular adenylate equilibrium. To test this hypothesis, we generated mice deficient in adenosine monophosphate deaminase 3 (AMPD3), the key catabolic enzyme for 5'-AMP in erythrocytes. Mice deficient in AMPD3 maintained AMPD activities in all tissues except erythrocytes. Developmentally and morphologically, the Ampd3(-/-) mice were indistinguishable from their wild type siblings. The levels of ATP, ADP but not 5'-AMP in erythrocytes of Ampd3(-/-) mice were significantly elevated. Fasting blood glucose levels of the Ampd3(-/-) mice were comparable to wild type siblings. In comparison to wild type mice, the Ampd3(-/-) mice displayed a deeper hypometabolism with a significantly delayed average arousal time in response to 5'-AMP administration. Together, these findings demonstrate a central role of AMPD3 in the regulation of 5'-AMP mediated hypometabolism and further implicate erythrocytes in this behavioral response.
Department of Biochemistry and Molecular Biology, University of Texas Health Science Center, Houston, Texas, United States of America.
Isadora Susan
IS
Daniels
William G
WG
O Brien
Vinay
V
Nath
Zhaoyang
Z
Zhao
Cheng Chi
CC
Lee
D000659:AMP Deaminase / Q000172:deficiency / Q000235:genetics*; D000249:Adenosine Monophosphate; D000818:Animals; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains
D000249:Adenosine Monophosphate; D000659:AMP Deaminase; C579174:AMPD3 protein, mouse