A role of erythrocytes in adenosine monophosphate initiation of hypometabolism in mammals.
Biochemical and mechanistic aspects into how various hypometabolic states are initiated in mammals are poorly understood. Here, we show how a state of hypometabolism is initiated by 5'-AMP uptake by erythrocytes. Wild type, ecto-5'-nucleotidase-deficient, and adenosine receptor-deficient mice undergo 5'-AMP-induced hypometabolism in a similar fashion. Injection of 5'-AMP leads to two distinct declining phases of oxygen consumption (VO(2)). The phase I response displays a rapid and steep decline in VO(2) that is independent of body temperature (T(b)) and ambient temperature (T(a)). It is followed by a phase II decline that is linked to T(b) and moderated by T(a). Altering the dosages of 5'-AMP from 0.25- to 2-fold does not change the phase I response. For mice, a T(a) of 15 degrees C is effective for induction of DH with the appropriate dose of 5'-AMP. Erythrocyte uptake of 5'-AMP leads to utilization of ATP to synthesize ADP. This is accompanied by increased glucose but decreased lactate levels, suggesting that glycolysis has slowed. Reduction in glycolysis is known to stimulate erythrocytes to increase intracellular levels of 2,3-bisphosphoglycerate, a potent allosteric inhibitor of hemoglobin's affinity for oxygen. Our studies showed that both 2,3-bisphosphoglycerate and deoxyhemoglobin levels rose following 5'-AMP administration and is in parallel with the phase I decline in VO(2). In summary, our investigations reveal that 5'-AMP mediated hypometabolism is probably triggered by reduced oxygen transport by erythrocytes initiated by uptake of 5'-AMP.
Daniels
Isadora Susan
IS
Department of Biochemistry and Molecular Biology, University of Texas Health Science Center, Houston, TX 77030, USA.
Zhang
Jianfa
J
O'Brien
William G
WG
Tao
Zhenyin
Z
Miki
Tomoko
T
Zhao
Zhaoyang
Z
Blackburn
Michael R
MR
Lee
Cheng Chi
CC
D019794:2,3-Diphosphoglycerate / Q000378:metabolism; D000227:Adenine Nucleotides / Q000302:isolation & purification; D000241:Adenosine / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000097:blood* / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006605:Hibernation / Q000502:physiology; D007700:Kinetics; D019344:Lactic Acid / Q000097:blood; D008322:Mammals; D008659:Metabolic Diseases / Q000097:blood*; D055442:Metabolome; D051379:Mice; D008810:Mice, Inbred C57BL; D010101:Oxygen Consumption; D013696:Temperature
D000227:Adenine Nucleotides; D019794:2,3-Diphosphoglycerate; D019344:Lactic Acid; D000249:Adenosine Monophosphate; D000241:Adenosine