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Copper is involved in several biological processes. The static and labile copper pools are controlled by means of a network of influx and efflux transporters, storage proteins, chaperones, transcription factors and small molecules as glutathione (GSH), which contributes to the cell reducing environment. To follow the fate of intracellular copper labile pool, a variant of human apocarbonic anhydrase has been proposed as fluorescent probe to monitor cytoplasmic Cu. Aware that in this cellular compartment copper ion is present as Cu, electron spin resonance technique (ESR) was used to ascertain whether (bovine or human) carbonic anhydrase (CA) was able to accommodate Cu in the same sites occupied by Cu, in the presence of naturally occurring reducing agents such as ascorbate and GSH. Our ESR results on Cu complexes with CA allow for a complete characterization of the two metal binding sites of the protein in solution. The use of the reported affinity constants of zinc in the catalytic site and of Cu in the peripheral and catalytic site, allow us to obtain the speciation of copper species mimicking the spectroscopic study conditions. The different Cu coordination features in the catalytic and the peripheral (the N-terminus cleft mouth) binding sites influence the chemical reduction effect of the two main naturally occurring reductants. Ascorbate reversibly reduces the Cu complex with CA, while glutathione irreversibly induces the formation of Cu complex with its oxidized form (GSSG). Our results questioned the use of CA as intracellular Cu sensor. Furthermore, translating these findings to intracellular environment, the conversion of GSH in GSSG can significantly alter the metallostasis.
This article was published in the following journal.
Name: Journal of inorganic biochemistry
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A cytosolic carbonic anhydrase isoenzyme found widely distributed in cells of almost all tissues. Deficiencies of carbonic anhydrase II produce a syndrome characterized by OSTEOPETROSIS, renal tubular acidosis (ACIDOSIS, RENAL TUBULAR) and cerebral calcification. EC 4.2.1.-
A membrane-bound carbonic anhydrase found in lung capillaries and kidney.
A carbonic anhydrase isoenzyme found in MITOCHONDRIA where it provides bicarbonate ions that are components in the urea cycle and in GLUCONEOGENESIS.
A cytosolic carbonic anhydrase isoenzyme primarily expressed in ERYTHROCYTES, vascular endothelial cells, and the gastrointestinal mucosa. EC 4.2.1.-
A cytosolic carbonic anhydrase isoenzyme primarily expressed in skeletal muscle (MUSCLES, SKELETAL). EC 4.2.1.-
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