Adenylate metabolism in the heart. Regulatory properties of rabbit cardiac adenylate deaminase

Barsacchi, Renata; Ranieri-Raggi, Maria; Bergamini, Christian; Raggi, Antonio

doi:10.1042/bj1820361

Cited by 30 publications

(21 citation statements)

References 22 publications

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“…Although both require millimolar K+ for full activity, the former is more readily activated by bivalent cations than the latter [9]. The apparent Km of 5.8 mM AMP for rabbit cardiac AMP deaminase is greater than the Km of 0.3-0.7 mM generally reported for (rabbit) skeletal-muscle AMP deaminase [29,35], implying that the cardiac isoform has much lower substrate affinity. AMP deaminase activity in enriched cardiac preparations reaches half-maximal reaction velocity at 2-13 mM AMP [23,24,27], suggestive of the low-millimolar Km that we have…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of AMP deaminase from mammalian (rabbit) myocardium

Thakkar¹,

Janero²,

Yarwood³

et al. 1993

Biochemical Journal

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AMP deaminase (AMP aminohydrolase, EC 3.5.4.6) is a ubiquitous enzyme in eukaryotes, which may play a role in ATP catabolism during myocardial ischaemia. We report isolation of AMP deaminase from rabbit myocardium with a 19% recovery and a 650-fold enrichment, using a newly devised protocol involving sequential cation-exchange, gel-permeation and affinity chromatographies. The cardiac AMP deaminase preparation described was electrophoretically and chromatographically homogeneous and contained one unique N-terminal residue (leucine). The isolated enzyme was sensitive to various cations (K+, Mg2+, Ca2+). The pH optimum of purified cardiac AMP deaminase was 6.8, its pI was 6.5, and it displayed substrate-specificity toward 5'-AMP. The subunit molecular mass of rabbit heart AMP deaminase on SDS/PAGE (81 kDa) and the holoenzyme molecular mass as estimated by non-denaturing size-exclusion h.p.l.c. (330 kDa) indicated that the native enzyme was a tetramer. Cardiac AMP deaminase displayed a sigmoidal substrate-saturation curve in the presence of 100 mM KCl. Apparent Michaelis constants were a Km of 5.8 mM AMP and a Vmax. of 11.1 mumol/min per mg of protein. ATP and ADP were positive allosteric effectors of cardiac AMP deaminase: the apparent Km was decreased to 1.7 mM by 1.0 mM ATP. The enzyme was inhibited by GTP, coformycin, coformycin 5'-phosphate, palmitoyl-CoA, inorganic phosphate compounds, and the metal chelator o-phenanthroline. No inhibition either by product nucleotide (IMP) or by nicotinamide nucleotides was detected when these agents were examined at concentrations up to 2.5 mM. We conclude that this enzyme preparation offers a means by which the kinetic mechanism and regulation of mammalian cardiac AMP deaminase may be directly investigated.

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Section: Discussionmentioning

confidence: 99%

Isolation and characterization of AMP deaminase from mammalian (rabbit) myocardium

Thakkar¹,

Janero²,

Yarwood³

et al. 1993

Biochemical Journal

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“…Deaminase activity of AMPD is known to be increased by optimal pH, ATP, ADP, NADH, and phosphorylation by PKC and to be inhibited by inorganic phosphate and GTP [30,31]. Since it has been reported that several PKC isoforms are activated in diabetic hearts [32] and that AMPD activity is increased in a model of type 1 diabetes mellitus (T1DM) [33], we examined possible role of PKC in increased AMPD activity in OLETF.…”

Section: Up-regulated Ampd Activity and Its Functional Impact In Diabmentioning

confidence: 99%

Excessive degradation of adenine nucleotides by up-regulated AMP deaminase underlies afterload-induced diastolic dysfunction in the type 2 diabetic heart

Kouzu

Miki

Tanno

et al. 2015

Journal of Molecular and Cellular Cardiology

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“…Removal of ATP and ADP or withdrawal of their inhibition by increases in Mg++ ions would increase the 5'-nucleotidase activity. Flux towards adenosine would be controlled by the relative activity of AMPda and 5'-nucleotidase, as is postulated for the rabbit heart (Barsacchi et al, 1979). From the above values of AMPda and 5"Kleotidase activity in rabbit arterial tissue, the flux on complete activation of both enzymes is expected to be towards adenosine.…”

mentioning

confidence: 98%

AMP deaminase histochemical activity and immunofluorescent isozyme localization in rat skeletal muscle.

Thompson

Sabina²,

Ogasawara³

et al. 1992

J Histochem Cytochem.

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The cellular distribution of AMP deaminase (AMPda) isozymes was documented for rat soleus and plantaris muscles, utilizing immunofluorescence microscopy and immunoprecipitation methods. AMPda is a ubiquitous enzyme existing as three distinct isozymes, A, B and C, which were initially purified from skeletal muscle, liver (and kidney), and heart, respectively. AMPda-A is primarily concentrated subsarcolemmally and intermyofibrillarly within muscle cells, while isozymes B and C are concentrated within non-myofiber elements of muscle tissue. AMPda-B is principally associated with connective tissues surrounding neural elements and the muscle spindle capsule, and AMPda-C is predominantly associated with circulatory elements, such as arterial and venous walls, capillary endothelium, and red blood cells. These specific localizations, combined with documented differences in kinetic properties, suggest multiple functional roles for the AMPda isozymes or temporal segregation of similar AMPda functions. Linkage of the AMPda substrate with adenosine production pathways at the AMP level and the localization of isozyme-C in vascular tissue suggest a regulatory role in the microcirculation.

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Adenylate metabolism in the heart. Regulatory properties of rabbit cardiac adenylate deaminase

Cited by 30 publications

References 22 publications

Isolation and characterization of AMP deaminase from mammalian (rabbit) myocardium

Isolation and characterization of AMP deaminase from mammalian (rabbit) myocardium

Excessive degradation of adenine nucleotides by up-regulated AMP deaminase underlies afterload-induced diastolic dysfunction in the type 2 diabetic heart

AMP deaminase histochemical activity and immunofluorescent isozyme localization in rat skeletal muscle.

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