Determinants of the S-Adenosylhomocysteine (SAH) Technique for the Local Assessment of Cardiac Free Cytosolic Adenosine

Loncar, Robert; Flesche, C. W.; Deußen, Andreas

doi:10.1006/jmcc.1996.0351

Cited by 20 publications

(20 citation statements)

References 3 publications

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“…7B). The reaction catalyzed by SAH-hydrolase is reversible, and the direction of its activity is dependent on the local concentrations of homocysteine [146]. The enzyme however, generally favours the hydrolysis of SAH as both homocysteine and adenosine are rapidly metabolized [147].…”

Section: Adenosine Metabolismmentioning

confidence: 99%

Adenosine kinase and ribokinase – the RK family of proteins

Park

Gupta

2008

Cell. Mol. Life Sci.

126

142

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Ribokinase (RK) and adenosine kinase (AK) catalyze the phosphorylation of ribose and adenosine to ribose-5-phosphate and AMP, respectively. Belonging to the RK family of proteins, these enzymes share a number of unique structural and functional elements. Extensive work has been carried out on many aspects of these enzymes in recent years, and we summarize the wealth of information currently available on them. The topics covered include descriptions of the primary and three-dimensional structures of AK and RK, their phylogenetic relationships, biochemical aspects of these enzymes including their reaction mechanisms and ionic requirements, and also work on certain inhibitors of these enzymes. The cellular metabolism and transport of ribose and adenosine are also briefly discussed, as well as the beneficial effects of ribose and adenosine in physiology and how these effects can be harnessed for pharmacological purposes.

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Section: Adenosine Metabolismmentioning

confidence: 99%

Adenosine kinase and ribokinase – the RK family of proteins

Park

Gupta

2008

Cell. Mol. Life Sci.

126

142

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“…The transmethylation (SAH) pathway also contributes relatively little to adenosine formation. Estimates in the guinea pig and dog place rates at 10-25% of total formation under baseline conditions (55, 180), and this relatively small proportion also declines with stress. Thus neither extracellular formation nor formation via SAH can explain disproportionate elevations in adenosine relative to [5Ј-AMP] during ischemia or hypoxia.…”

Section: Generation Of Endogenous Adenosine During Insultmentioning

confidence: 99%

Acute adenosinergic cardioprotection in ischemic-reperfused hearts

Headrick

Hack

Ashton

2003

American Journal of Physiology-Heart and Circulatory Physiology

150

164

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. Acute adenosinergic cardioprotection in ischemic-reperfused hearts. Am J Physiol Heart Circ Physiol 285: H1797-H1818, 2003; 10.1152/ajpheart.00407. 2003.-Cells of the cardiovascular system generate and release purine nucleoside adenosine in increasing quantities when constituent cells are "stressed" or subjected to injurious stimuli. This increased adenosine can interact with surface receptors in myocardial, vascular, fibroblast, and inflammatory cells to modulate cellular function and phenotype. Additionally, adenosine is rapidly reincorporated back into 5Ј-AMP to maintain the adenine nucleotide pool. Via these receptor-dependent and independent (metabolic) paths, adenosine can substantially modify the acute response to ischemic insult, in addition to generating a more sustained ischemia-tolerant phenotype (preconditioning). However, the molecular basis for acute adenosinergic cardioprotection remains incompletely understood and may well differ from more widely studied preconditioning. Here we review current knowledge and some controversies regarding acute cardioprotection via adenosine and adenosine receptor activation.adenosine; adenosine receptor activation; ischemia; reperfusion injury THE HEART possesses its own intrinsic protective responses, including the adenosine receptor system, which enhance resistance to ischemic insult. An understanding of the mechanisms involved in these responses not only informs us of how the heart reacts to injurious stimuli, but may provide avenues for developing novel protective strategies applicable in the setting of ischemia-reperfusion. The purine nucleoside adenosine was attributed with cardioregulatory functions almost 75 years ago (64), and since then has emerged as a crucially important control substance in essentially every tissue of the body. In the heart adenosine not only plays a role in regulating growth and differentiation, angiogenesis, coronary blood flow, cardiac conduction and heart rate, substrate metabolism, and sensitivity to adrenergic stimulation (23,67,68,73,74,260,271,283), but may play a role as an endogenous determinant of ischemic tolerance (189,225,245,259,311,312,318). From a therapeutic viewpoint, adenosine-based therapies protect against ischemic injury in a variety of animal models (72,177,208,265,288) and in human cardiac tissue (34, 36, 37,240,296). However, much remains unclear regarding the roles and mechanisms of action of adenosine in producing acute protection against ischemia and reperfusion. Generation of Endogenous Adenosine During InsultEndogenous adenosine levels increase rapidly with ischemic insult (104,109,285,286) to mediate a retaliatory response. This protective pool of adenosine can be formed via dephosphorylation of 5Ј-AMP by intra-and extracellular 5Ј-nucleotidases and from S-adenosylhomocysteine (SAH) via SAH hydrolase. Extracellular adenosine is rapidly taken into cells via a facilitative transporter (131). Within cells it is either deaminated by adenosine deaminase or rephosphorylated to 5Ј-AMP via adenosine kinase. O...

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“…According to previously published standardized methods, the myocardial tissue was freeze-dried and dissected into 256 samples with an average dry mass of Ϸ25 mg. 22 For measurement of metabolite concentrations (SAH, ATP, ADP, homocysteine, lactate, pyruvate), acid extracts were prepared. 15,19 An aliquot of the acidic supernatant was used for later measurement of the homocysteine concentration, and the remaining aliquot was neutralized for the analysis of the other metabolites.…”

Section: Analytical Proceduresmentioning

confidence: 99%

Coronary Reserve of High- and Low-Flow Regions in the Dog Heart Left Ventricle

1998

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Background-Left ventricular myocardial blood flow is spatially heterogeneous. The hypothesis we tested was whether myocardial areas with a steady-state flow Ͻ0.5 times mean flow are underperfused and areas with flow Ͼ1.5 times mean flow are overperfused. Methods and Results-In anesthetized beagle dogs (nϭ10), the relationship between local blood flow versus S-adenosylhomocysteine (SAH) concentration, a measure of the free intracellular adenosine concentration, and lactate, a measure of the myocardial NADH/NAD ϩ ratio, were determined under control conditions and after coronary constriction. Control local myocardial blood flow was 0.99Ϯ0.46 mL ⅐ min Ϫ1 ⅐ g Ϫ1 , with a coefficient of variation of 0.36Ϯ0.12 (nϭ256 per heart; sample wet mass, 125Ϯ30 mg). Tissue concentrations of SAH (3.4Ϯ2.5 nmol/g) and lactate (1.88Ϯ0.80 mol/g) were not elevated in low-flow samples. However, after coronary artery constriction, poststenotic blood flow decreased from 1.00Ϯ0.27 to 0.49Ϯ0.22 mL ⅐ min Ϫ1 ⅐ g Ϫ1 (PϽ0.04), with significant correlation between local SAH and flow (rϭϪ0.59) and lactate and flow (rϭϪ0.50). Although nearly all samples from control high-flow regions showed increased SAH concentrations if relative flow after stenosis was Ͻ1.0, control low-flow samples frequently displayed low SAH concentrations. The percent reduction in flow determined the changes in the local SAH and lactate concentration, independent of the local control blood flow. Conclusions-When the coronary inflow is unrestricted, the oxygen supply to control low-flow regions meets metabolic demand. Flow to control high-flow regions reflects a higher local demand rather than overperfusion. Thus, blood flow heterogeneity most likely reflects differences in aerobic metabolism. (Circulation. 1998;98:262-270.)

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Determinants of the S-Adenosylhomocysteine (SAH) Technique for the Local Assessment of Cardiac Free Cytosolic Adenosine

Cited by 20 publications

References 3 publications

Adenosine kinase and ribokinase – the RK family of proteins

Adenosine kinase and ribokinase – the RK family of proteins

Acute adenosinergic cardioprotection in ischemic-reperfused hearts

Coronary Reserve of High- and Low-Flow Regions in the Dog Heart Left Ventricle

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