Implication of CO inactivation on myoglobin function

2006 ◽  
Vol 290 (6) ◽  
pp. C1616-C1624 ◽  
Author(s):  
Youngran Chung ◽  
Shih-Jwo Huang ◽  
Alan Glabe ◽  
Thomas Jue

Myoglobin (Mb) has a purported role in facilitating O2 diffusion in tissue, especially as cellular Po2 drops or the respiration demand increases. Inhibiting Mb with CO under conditions that accentuate the facilitated diffusion role should then elicit a significant physiological response. In one set of experiments, the perfused myocardium received buffer with decreasing Po2 (225, 129, and 64 mmHg). Intracellular Po2 declined, as reflected in the 1H NMR Val E11 signal of MbO2 (67%, 32%, and 18%). The addition of 6% CO further reduced the available MbO2 (11%, 9%, and 7%), as evidenced by the decline of the MbO2 Val E11 signal intensity at −2.76 ppm. In a second set of experiments, electrical stimulation increased the heart rate (300, 450, and 540 beats/min) and correspondingly the O2 consumption rate (MV̇o2). Intracellular Po2 also declined, as reflected in the slight drop in the MbO2 signal (100%, 96%, and 82%). MV̇o2 increased (100%, 114%, 165%). The addition of 3% CO in the stimulated hearts further decreased the available MbO2 (46%, 44%, and 29%). In all cases, CO inactivation of Mb does not induce any change in the respiration rate, contractile function, and high-energy phosphate levels. Moreover, the MbCO/MbO2 partition coefficient shifts dramatically from its in vitro value during hypoxia and increased work. The observation suggests a modulation of an intracellular O2 gradient. Overall, the experimental observations provide no evidence of a facilitated diffusion role for Mb in perfused myocardium and implicate a physiologically responsive intracellular O2 gradient.

1976 ◽  
Vol 230 (6) ◽  
pp. 1744-1750 ◽  
Author(s):  
TB Allison ◽  
SP Bruttig ◽  
Crass MF ◽  
RS Eliot ◽  
JC Shipp

Significant alterations in heart carbohydrate and lipid metabolism are present 48 h after intravenous injection of alloxan (60 mg/kg) in rats. It has been suggested that uncoupling of oxidative phosphorylation occurs in the alloxanized rat heart in vivo, whereas normal oxidative metabolism has been demonstrated in alloxan-diabetic rat hearts perfused in vitro under conditions of adequate oxygen delivery. We examined the hypothesis that high-energy phosphate metabolism might be adversely affected in the alloxan-diabetic rat heart in vivo. Phosphocreatine and ATP were reduced by 58 and 45%, respectively (P is less than 0.001). Also, oxygen-dissociation curves were shifted to the left by 4 mmHg, and the rate of oxygen release from blood was reduced by 21% (P is less than 0.01). Insulin administration normalized heart high-energy phosphate compounds. ATP production was accelerated in diabetic hearts perfused in vitro with a well-oxygenated buffer. These studies support the hypothesis that oxidative ATP production in the alloxan-diabetic rat heart is reduced and suggest that decreased oxygen delivery may have a regulatory role in the oxidative metabolism of the diabetic rat heart.


1963 ◽  
Vol 18 (6) ◽  
pp. 1105-1110 ◽  
Author(s):  
L. O. Pilgeram ◽  
D. A. Loegering

A possible role for cellular energy metabolism in the control of the blood clotting mechanism has been shown. High-energy phosphate was found to strongly inhibit the recalcification time of plasma prepared with siliconized or glass surfaces. The nucleotide, adenosine triphosphate, in crystalline form and chromatographically pure, will inhibit or completely prevent coagulation in vitro. Reactivity is based primarily on the high-energy phosphate linkage and secondarily upon the nucleoside, adenosine. The principal site of action for ATP is on an unidentified precursor of thromboplastin. Available evidence indicates an important role for energy metabolism in the cellular mechanisms which effect a control over thromboplastin generation and its possible thrombotic and arteriosclerotic sequelae. cellular control mechanisms; blood fluidity; thrombosis arteriosclerosis; aging Submitted on July 1, 1963


1970 ◽  
Vol 118 (5) ◽  
pp. 791-800 ◽  
Author(s):  
C. T. Jones ◽  
P. Banks

1. Chopped tissue from guinea-pig cerebral cortex carried out an energy-dependent incorporation of [14C]valine into protein. 2. At all times studied the nuclear fraction of the homogenized tissue accounted for about 25% of the total labelled protein. 3. Electrical stimulation at first increased, but subsequently decreased, the rate of incorporation of [14C]valine into protein of the chopped tissue. 4. The initial increase in the incorporation of [14C]valine into protein occurred in the nuclear fraction. At later times electrical stimulation decreased the incorporation into all the subcellular fractions, but the relative contribution of the nuclear fraction to the total labelled protein increased. 5. These changes are discussed in relation to the changes in the rates of respiration, glycolysis, high-energy phosphate content and intracellular Na+ and K+ concentrations, which were measured under the same experimental conditions as those used to study protein synthesis.


1991 ◽  
Vol 261 (6) ◽  
pp. H1919-H1926
Author(s):  
M. Osbakken ◽  
D. N. Zhang ◽  
D. Nelson ◽  
M. Erecinska

Feeding Sprague-Dawley rats for 3 wk a diet containing 1% by weight of cyclocreatine increased the reservoir of the high-energy phosphate compounds but also caused alterations in the levels of the two key amino acids, aspartate and glutamate. Both were decreased by approximately 50% in the presence of an unaltered content of glutamine. In vitro exposure of these hearts to sequential perfusion, global ischemia, and reperfusion in the absence of added amino acids resulted in changes in aspartate, glutamate, and glutamine that were different from those in hearts from control rats. In the cyclocreatine-fed group, aspartate concentration ([aspartate]) and [glutamate] fell after global ischemia, whereas [glutamine] was unaltered. [Glutamine] decreased, however, in the reperfusion period. In control hearts, the predominant effect was a steady decline in glutamine, which was accompanied by either less than 10% (after global ischemia) or 30-50% fall (after reperfusion) in [aspartate] and [glutamate]. The concentration of tissue Pi was smaller in hearts from cyclocreatine-fed rats and appeared to increase more slowly during ischemia. In the presence of rotenone and aminooxyacetate, heart homogenates catalyzed production of glutamate from glutamine, which was markedly stimulated by Pi and inhibited by H+. It is postulated that 1) phosphate-activated glutaminase is an important enzyme that determines cardiac [glutamate], 2) lower [phosphate] in hearts from rats fed cyclocreatine is responsible for the apparently lesser activity of glutaminase, 3) breakdown of the high-energy phosphate compounds and consequent rise in Pi activates glutaminase, and 4) slow breakdown of glutamine during global ischemia is a result of inhibition of glutaminase by H+.


2016 ◽  
Vol 310 (2) ◽  
pp. H226-H238 ◽  
Author(s):  
Youngran Chung

Reperfused hypertrophic hearts are prone to develop reflow abnormalities, which are likely to impair O2 return to the myocardium. Yet, reflow deficit may not be the only factor determining postischemic oxygenation in the hypertrophic heart. Altered O2 demand may also contribute to hypoxia. In addition, the extent to which myocardial Po2 dictates energy and functional recovery in the reperfused heart remains uncertain. In the present study, moderately hypertrophied hearts from spontaneously hypertensive rats were subjected to ischemia-reperfusion, and the recovery time courses of pH and high-energy phosphates were followed by 31P NMR. 1H NMR measurement of intracellular myoglobin assessed tissue O2 levels. The present study found that the exacerbation of hypoxia in the postischemic spontaneously hypertensive rat heart arises mostly from impaired microvascular supply of O2. However, postischemic myocardial Po2, at least when it exceeds ∼18% of the preischemic level, does not limit mitochondrial respiration and high-energy phosphate resynthesis. It only passively reflects changes in the O2 supply-demand balance.


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