RESUMO
BACKGROUND AND AIM: The present study investigated the influence of liver tumor structure on life expectancy in dogs. Diseases of the liver comprise 5-25% of all non-communicable diseases in dogs, and primary hepatic tumors account for 0.6-1.3% of tumors. This research aimed to study the post-operative life span of animals with primary or metastatic tumors of the liver. MATERIALS AND METHODS: During the study period, 7124 oncological operations were performed in our clinic. In total, 128 liver tumors were detected in live animals, while 323 were detected posthumously. Forty animals underwent surgery for various liver tumors. In dogs with primary liver tumors, the average age was 11.9 years and the average body weight was 15.5 kg, while in dogs with liver metastases, the mean age was 11.4 years and the average body weight was 24 kg. RESULTS: The ratio of males to females among dogs with primary liver tumors was about 1:1 (ten females and nine males), while that among dogs with metastatic liver damage was clearly predominantly female (14 females and two males) because females often undergo surgery for cancerous mammary glands or ovaries. CONCLUSION: The size of tumors and the number of affected lobes had a significant effect on the post-operative life span. With a tumor size of <5 cm and a lesion covering less than two lobes of the liver, life expectancy was significantly longer and the prognosis was more favorable. In cases of large tumors or those affecting more than two lobes, life expectancy was significantly reduced and the prognosis was cautious to unfavorable.
RESUMO
gamma-Glultamylcysteine synthetase (gamma-GCS) catalyzes the first step in the de novo biosynthesis of glutathione. In trypanosomes, glutathione is conjugated to spermidine to form a unique cofactor termed trypanothione, an essential cofactor for the maintenance of redox balance in the cell. Using extensive similarity searches and sequence motif analysis we detected homology between gamma-GCS and glutamine synthetase (GS), allowing these proteins to be unified into a superfamily of carboxylate-amine/ammonia ligases. The structure of gamma-GCS, which was previously poorly understood, was modeled using the known structure of GS. Two metal-binding sites, each ligated by three conserved active site residues (n1: Glu-55, Glu-93, Glu-100; and n2: Glu-53, Gln-321, and Glu-489), are predicted to form the catalytic center of the active site, where the n1 site is expected to bind free metal and the n2 site to interact with MgATP. To elucidate the roles of the metals and their ligands in catalysis, these six residues were mutated to alanine in the Trypanosoma brucei enzyme. All mutations caused a substantial loss of activity. Most notably, E93A was able to catalyze the l-Glu-dependent ATP hydrolysis but not the peptide bond ligation, suggesting that the n1 metal plays an important role in positioning l-Glu for the reaction chemistry. The apparent K(m) values for ATP were increased for both the E489A and Q321A mutant enzymes, consistent with a role for the n2 metal in ATP binding and phosphoryl transfer. Furthermore, the apparent K(d) values for activation of E489A and Q321A by free Mg(2+) increased. Finally, substitution of Mn(2+) for Mg(2+) in the reaction rescued the catalytic deficits caused by both mutations, demonstrating that the nature of the metal ligands plays an important role in metal specificity.
