China
Africa
Explore chapters and articles related to this topic
Orotic aciduria
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
The conceptualization of effective replacement therapy began with the first publication [1]. Administration of uridylic and cytidylic acids led to reduction in orotic acid excretion. This was presumably a consequence of breakdown in the intestine to uridine and cytidine, as oral bioavailability of nucleotides is very low, and their administration usually results in diarrhea. Uridine therapy was initiated by Becroft and Phillips in the second patient [2]. Treatment begun at 16 months with 1.5 g/day led to a prompt rise in hemoglobin and a normal bone marrow. Activity and interest in his surroundings improved immediately, as did appetite. Hair and nails began to grow, as did he, crossing percentile lines for weight from below the 3rd percentile to between the 90th and 97th percentile. He remained mildly mentally impaired, but there was no progression. It was interesting that he experienced a prompt relapse on substitution of uracil for uridine, even though the content of pyrimidine base was twice that of uridine, which at that time was 75 mg/kg. Uridine therapy is dependent for bioavailability on efficient intestinal absorption and the activity of the salvage enzyme uridine kinase (EC2.7.1.48) which leads directly to the formation of the nucleotide UMP [25, 26].
Mechanisms of Resistance to Antineoplastic Drugs
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
Philip J. Vickers, Alan J. Townsend, Kenneth H. Cowan
The transformation of the pyrimidine analog 5-fluorouracil (5-FU) to its various active metabolites is a complex process, involving a number of biochemical pathways (Figure 2). The active metabolites generated in these reactions are potentially cytotoxic by inhibition of thymidylate synthase or through incorporation into RNA or DNA.25-28 Decreased activation of 5-FU resulting from decreased levels of uridine kinase,16 orotic acid phosphoribosyl transferase,17,18 and uridine phosphorylase19 have all been reported in cells resistant to 5-FU.
Colon Carcinogenesis: Biochemical Changes
Published in Herman Autrup, Gary M. Williams, Experimental Colon Carcinogenesis, 2019
Young S. Kim, Laurence J. Mcintyre
The study of enzyme changes in colon carcinogenesis, in addition to investigating individual enzymes in detail, has also been concerned with the patterns of key enzyme levels in the control of intermediary metabolism. Shonk et al.19 measured the levels of the enzymes involved in glycolysis in normal human colon and colonic cancer tissue. They found that all the enzymes in glycolysis were elevated in the tumor tissue. This is in agreement with the common finding in malignant tissues that the respiratory enzyme activities are at the bottom of the range present in normal tissue, while the glycolytic enzyme activities are at the top end of the normal range.20 These studies were extended using a transplantable colon adenocarcinoma compared with normal colonic mucosa in the mouse.21 When the enzymes of pyrimidine metabolism were measured in normal colon, CTP synthetase activity was an order of magnitude lower than the other enzymes, suggesting that it was rate-limiting. It is interesting to note that in the cancer tissue this enzyme showed a higher increase than any of the others — 927% of the normal mucosa activity. This study also demonstrated that the colonic tumor cells displayed reciprocal regulation. This type of regulation is based on the fact that one way of increasing the supply of metabolic intermediates is not only to increase the synthetic enzyme activity but also to concomitantly reduce the level of the corresponding catabolic enzyme. This is seen in the increase in uridine kinase and the decrease in uridine Phosphorylase as well as in the increase in thymidine kinase and the decrease in dihydrothymine dehydrogenase. The most striking example of reciprocal regulation is in glutamine PRPP amidotransferase and xanthine oxidase where the ratio of synthetic to catabolic enzymes is increased 81-fold by the changes.
Benzenesulfonamide derivatives as Vibrio cholerae carbonic anhydrases inhibitors: a computational-aided insight in the structural rigidity-activity relationships
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Marialuigia Fantacuzzi, Ilaria D’Agostino, Simone Carradori, Francesco Liguori, Fabrizio Carta, Mariangela Agamennone, Andrea Angeli, Filomena Sannio, Jean-Denis Docquier, Clemente Capasso, Claudiu T. Supuran
Moreover, as assessed through the STRING web tool (https://string-db.org/ accessed on March 4th, 2022)27, VchCAs participate in several functional and physical protein-protein association networks, such as proteins belonging to the sulfate permease family, those involved in the degradation of long-chain fatty acids, fumarate hydratase, uridine kinase, etc. Relevantly, VchCAs also seem to be associated with the thioredoxin system, fundamental in the physiology and pathogenesis of bacteria due to its influence on the expression of many genes, in the reduction of cytoplasmic proteins and hydrogen peroxide and, in general, cell division, energy transduction, oxidative stress response, transcriptional regulation, phage assembly and propagation28.