Abstract
Considering that thiol-containing enzymes like kinases are critical for several metabolic pathways and energy homeostasis, we investigated the effects of cystine dimethyl ester and/or cysteamine administration on kinases crucial for energy metabolism in the kidney of Wistar rats. Animals were injected twice a day with 1.6 µmol/g body weight cystine dimethyl ester and/or 0.26 µmol/g body weight cysteamine from the 16th to the 20th postpartum day and euthanized after 12 hours. Pyruvate kinase, adenylate kinase, creatine kinase activities and thiol/disulfide ratio were determined. Cystine dimethyl ester administration reduced thiol/disulfide ratio and inhibited the kinases activities. Cysteamine administration increased the thiol/disulfide ratio and co-administration with cystine dimethyl ester prevented the inhibition of the enzymes. Regression between the thiol/disulfide ratio, and the kinases activities were significant. These results suggest that redox status may regulate energy metabolism in the rat kidney. If thiol-containing enzymes inhibition and oxidative stress occur in patients with cystinosis, it is possible that lysosomal cystine depletion may not be the only beneficial effect of cysteamine administration, but also its antioxidant and thiol-protector effect.
Highlights
A variety of metabolic processes has been shown to be altered significantly under conditions in which the thiol/disulfide ratio changes
Two-ways ANOVA showed no interaction between CDME and CSH in body weight [F (1, 25) = 1.62; p > 0.05], kidney weight [F (1, 25) = 1.26; p > 0.27], as well as protein content [F (1, 25) = 0.57; p > 0.45] at the end of the treatment, indicating that the biochemical differences observed between the groups cannot be attributed to protein loss
We investigated the effects of the administration of CDME, CSH, or CDME + CSH on Pyruvate kinase (PK), adenylate kinase (AK), and creatine kinase (CK) activities of the kidney from young rats
Summary
A variety of metabolic processes has been shown to be altered significantly under conditions in which the thiol/disulfide ratio changes. The activity of some enzymes can be modified by the Pyruvate kinase (PK; EC 2.7.1.40), creatine kinase (CK; EC 2.7.3.2) and adenylate kinase (AK; EC 2.7.4.3) are thiol-containing enzymes critical for energy metabolism in several mammalian tissues. CK is a thiol-containing enzyme that catalyzes the reversible transfer of the phosphoryl group from phosphocreatine to ADP, regenerating ATP. There are distinct CK isoenzymes, which are compartmentalized in the places where energy is liberated (mitochondria) or utilized (cytosol) (Wallimann et al 1992). AK catalyzes the reversible transfer of phosphoryl between ATP, ADP, and AMP (Prices et al 1975). AK, PK, and CK are critical for the enzymatic phosphoryl transfer network, in other words, responsible for the transfer of the γ-phosphoryl of ATP from mitochondria to the cytosol (Dzeja and Terzic 2003)
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