title: A role of erythrocytes in adenosine monophosphate initiation of hypometabolism in mammals.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Health Science Center, Houston, TX 77030, USA.
authors.forename: Isadora Susan
authors.initials: IS
authors.lastname: Daniels
authors.forename: Jianfa
authors.initials: J
authors.lastname: Zhang
authors.forename: William G
authors.initials: WG
authors.lastname: O'Brien
authors.forename: Zhenyin
authors.initials: Z
authors.lastname: Tao
authors.forename: Tomoko
authors.initials: T
authors.lastname: Miki
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Michael R
authors.initials: MR
authors.lastname: Blackburn
authors.forename: Cheng Chi
authors.initials: CC
authors.lastname: Lee
mesh_terms: 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
chemical_list: D000227:Adenine Nucleotides; D019794:2,3-Diphosphoglycerate; D019344:Lactic Acid; D000249:Adenosine Monophosphate; D000241:Adenosine