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Role of troponin T and AMP deaminase in the modulation of skeletal muscle contraction
No full textIn fast muscle, isoforms of troponin T (TnT) contain an N-terminal hypervariable region that does not bind any protein of the thin filament. The N-terminal domain of TnT is removed by calpain during stress conditions and so could modulate the role of TnT in the regulation of contraction by affecting the TnT-binding affinity for tropomyosin (Tm) depending on the sequence and charge within the domain. During skeletal muscle contraction, the myokinase reaction is displaced by AMP deaminase (AMPD), an allosteric metalloenzyme, toward the formation of ATP. An unrestrained AMPD activity follows the proteolytic cleavage of the enzyme in vivo that releases a 97 aa N-terminal fragment, removing the inhibition exerted by the binding of ATP to a zinc site in the N-terminal region. Rabbit fast TnT or its phosphorylated 50-aa residue N-terminal peptide restores in AMPD the inhibition by ATP, removed in vitro by the release of a 95 aa N-terminal fragment by trypsin. Since the N-terminal region of fast rabbit TnT contains a putative zinc-binding motif, it can be inferred that TnT mimics the regulatory action exerted in native AMPD by the N-terminal domain that holds the enzyme in a less active conformation due to the presence of a zinc ion connecting the N-terminal and C-terminal regions. Together with evidence that AMPD is localized on the myofibril, the data reported in this review on the interactions between AMPD and TnT strongly suggest that these proteins mutually combine to fine-tune the regulation of muscle contraction in fast muscle
Structure-function relationships in mammalian histidine-proline-rich glycoprotein
No full textHistidine-proline-rich glycoprotein (HPRG), or histidine-rich glycoprotein (HRG), is a serum protein that is synthesized in the liver and is actively internalised by different cells, including skeletal muscle. The multidomain arrangement of HPRG comprises two modules at the N-terminus that are homologous to cystatin but void of cysteine proteinase inhibitor function, and a second half consisting of a histidine-proline-rich region (HPRR) located between two proline-rich regions (PRR1 and PRR2), and a C-terminus domain. HPRG has been reported to bind various ligands and to modulate angiogenesis via the histidine residues of the HPRR. However, the secondary structure prediction of the HPRR reveals that more than 98% is disordered and the structural basis of the hypothesized functions remains unclear. Comparison of the PRR1 of several mammalian species indicates the presence of a conserved binding site that might coordinate the Zn(2+) ion with an amino acid arrangement compatible with the cysteine-containing site that has been identified experimentally for rabbit HPRG. This observation provides a structural basis to the function of HPRG as an intracellular zinc chaperone which has been suggested by the involvement of the protein in the maintenance of the quaternary structure of skeletal muscle AMP deaminase (AMPD). During Anthropoidea evolution, a change of the primary structure of the PRR1 Zn(2+) binding site took place, giving rise to the sequence M-S-C-S/L-S/R-C that resembles the MxCxxC motif characteristic of metal transporters and metallochaperones
Estrogenic and anti-estrogenic activity of two plant essential oils used in the food industry: a preliminary evaluation.
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Role of the interaction between troponin T and AMP deaminase by zinc bridge in modulating muscle contraction and ammonia production
No full textThe N-terminal region of troponin T (TnT) does not bind any protein of the contractile machinery and the role of its hypervariability remains uncertain. In this review we report the evidence of the interaction between TnT and AMP deaminase (AMPD), a regulated zinc enzyme localized on the myofibril. In periods of intense muscular activity, a decrease in the ATP/ADP ratio, together with a decrease in the tissue pH, is the stimulus for the activation of the enzyme that deaminating AMP to IMP and NH3 displaces the myokinase reaction towards the formation of ATP. In skeletal muscle subjected to strong tetanic contractions, a calpain-like proteolytic activity produces the removal in vivo of a 97-residue N-terminal fragment from the enzyme that becomes desensitized towards the inhibition by ATP, leading to an unrestrained production of NH3. When a 95-residue N-terminal fragment is removed from AMPD by trypsin, simulating in vitro the calpain action, rabbit fast TnT or its phosphorylated 50-residue N-terminal peptide binds AMPD restoring the inhibition by ATP. Taking in consideration that the N-terminus of TnT expressed in human as well as rabbit white muscle contains a zinc-binding motif, we suggest that TnT might mimic the regulatory action of the inhibitory N-terminal domain of AMPD due to the presence of a zinc ion connecting the N-terminal and C-terminal regions of the enzyme, indicating that the two proteins might physiologically associate to modulate muscle contraction and ammonia production in fast-twitching muscle under strenuous conditions
Regulation of skeletal muscle AMP deaminase: involvement of histidine residues in the pH-dependent inhibition of the rabbit enzyme by ATP
Full text linkL-carnitine and coenzyme Q10 protective action against ischemia and reperfusion of working rat heart
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Effect of MEN 10755, a new disaccharide analogue of doxorubicin, on sarcoplasmic reticulum Ca(2+) handling and contractile function in rat heart
No full textEffect of carnitine and coenzyme Q10 on the calcium uptake in heart sarcoplasmic reticulum of rats treated with anthracyclines
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