That was then, this is now: the development of our knowledge and understanding of P2 receptor subtypes

P2 receptors are present in virtually all tissues and cell types in the human body, and they mediate the physiological and pharmacological actions of extracellular purine and pyrimidine nucleotides. They were first characterised and named by Geoff Burnstock in 1978, then subdivided into P2X and P2Y purinoceptors in 1985 on the basis of pharmacological criteria in functional studies on native receptors. Molecular cloning of receptors in the 1990s revealed P2X receptors to comprise seven different subunits that interact to produce functional homo- and heterotrimeric ligand-gated cation channels. A family of eight P2Y G protein–coupled receptors were also cloned, which can form homo- and heterodimers. Deep insight into the molecular mechanisms of agonist and antagonist action has been provided by more recent determination of the tertiary and quaternary structures of several P2X and P2Y receptor subtypes. Agonists and antagonists that are highly selective for individual subtypes are now available and some are in clinical use. This has all come about because of the intelligence, insight and drive of the force of nature that was Geoff Burnstock.

BIOCHEMICAL STUDY OF CERTAIN ENZYMES IN DENGUE FEVER PATIENTS

Objective: The main objective of the present study is to correlate the effect of certain enzymes in diagnosis of dengue fever (DF) and impact of these elevated/decreased blood levels of enzymes on patients of DF. Methods: The study was carried out on 30 patients suspected to be suffering from DF. Blood sample was collected and tested for various parameters such as protein (albumin), lactate dehydrogenase (LDH), creatinine kinase (CK), C-reactive protein (CRP), acid phosphatase, alkaline phosphatase, serum glutamic oxaloacetic transaminase (SGOT), and serum glutamic pyruvic transaminase (SGPT). Results: Serum enzymes such as LDH and CK were found to be elevated to be a good marker of muscle damage and progression of diseases. CRP as a marker of inflammation was also found to be elevated. Enzymes like acid phosphatase increased abruptly while alkaline phosphatase was irregular. Liver enzymes SGOT and SGPT activity were also enhanced. Conclusion: Increased level of transaminases can be reflective of the formation of various amino acids for the synthesis of new protein and for channeling of glutamate and aspartate along with glycine for the synthesis of purine and pyrimidine nucleotides. Objective: The main objective of the present study is to correlate the effect of certain enzymes in diagnosis of dengue fever (DF) and impact of these elevated/decreased blood levels of enzymes on patients of DF. Methods: The study was carried out on 30 patients suspected to be suffering from DF. Blood sample was collected and tested for various parameters such as protein (albumin), lactate dehydrogenase (LDH), creatinine kinase (CK), C-reactive protein (CRP), acid phosphatase, alkaline phosphatase, serum glutamic oxaloacetic transaminase (SGOT), and serum glutamic pyruvic transaminase (SGPT). Results: Serum enzymes such as LDH and CK were found to be elevated to be a good marker of muscle damage and progression of diseases. CRP as a marker of inflammation was also found to be elevated. Enzymes like acid phosphatase increased abruptly while alkaline phosphatase was irregular. Liver enzymes SGOT and SGPT activity were also enhanced. Conclusion: Increased level of transaminases can be reflective of the formation of various amino acids for the synthesis of new protein and for channeling of glutamate and aspartate along with glycine for the synthesis of purine and pyrimidine nucleotides.

Geochemical influences on nonenzymatic oligomerization of prebiotically relevant cyclic nucleotides

The spontaneous emergence of RNA on the early Earth continues to remain an enigma in the field of origins of life. Few studies have looked at the nonenzymatic oligomerization of cyclic nucleotides under neutral to alkaline conditions, in fully dehydrated state. Herein, we systematically investigated the oligomerization of cyclic nucleotides under prebiotically relevant conditions, where starting reactants were subjected to repeated dehydration-rehydration (DH-RH) regimes, like they would have been on an early Earth. DH-RH conditions, a recurring geological theme, are driven by naturally occurring processes including diurnal cycles and tidal pool activity. These conditions have been shown to facilitate uphill oligomerization reactions in terrestrial geothermal niches, which are hypothesized to be pertinent sites for the emergence of life. 2′-3′ and 3′-5′ cyclic nucleotides of one purine-based (adenosine) and one pyrimidine-based (cytidine) system were evaluated in this study. Additionally, the effect of amphiphiles was also investigated. Furthermore, to discern the effect of ‘realistic’ conditions on this process, the reactions were also performed using hot spring water samples from an early Earth analogue environment. Our results showed that the oligomerization of cyclic nucleotides under DH-RH conditions resulted in intact informational oligomers. Amphiphiles increased the stability of, both, the starting monomers and the resultant oligomers. In analogue condition reactions, oligomerization of nucleotides and back-hydrolysis of the resultant oligomers was pronounced. Altogether, this study demonstrates how nonenzymatic oligomerization of cyclic purine and pyrimidine nucleotides, under laboratory-simulated and early Earth analogous conditions, could have resulted in RNA oligomers of a putative RNA World.

Cloning, expression, purification, crystallization and preliminary X-ray diffraction studies of NAD synthetase from methicillin-resistantStaphylococcus aureus

Staphylococcus aureusis an important human and animal pathogen that causes a wide range of infections. The prevalence of multidrug-resistantS. aureusstrains in both hospital and community settings makes it imperative to characterize new drug targets to combatS. aureusinfections. In this context, enzymes involved in NAD metabolism and synthesis are significant drug targets as NAD is a central player in several cellular processes. NAD synthetase catalyzes the last step in the biosynthesis of nicotinamide adenine dinucleotide, making it a crucial intermediate enzyme linked to the biosynthesis of several amino acids, purine and pyrimidine nucleotides, coenzymes and antibiotics.

Glutamine as a Feed Supplement for Piglets: a Review / Glutamina jako dodatek do paszy dla prosiąt: przegląd

Weaning is a crucial moment in a piglet’s life. It is characterized by a generally low nutrient intake and adverse changes in the small intestinal mucosa. Proper feeding is therefore necessary to ensure normal development of the gastrointestinal tract. One substance that could provide intestinal epithelial cells with necessary energy is the amino acid glutamine. It improves epithelium structure and accelerates the growth of intestinal villi in which nutrients are absorbed, thus improving feed utilization and growth performance in piglets. The effect of glutamine on intestinal microflora also improves animal health. In addition to liver and kidneys, small intestine is the main site of glutamine metabolism, which leads to the synthesis of purine and pyrimidine nucleotides and of the important antioxidant glutathione. Glutamine is also a precursor for the synthesis of proline and arginine, the components of body proteins. Glutamine downregulates the expression of genes responsible for oxidative stress and immune activation, and increases the expression of genes that are necessary for cell growth and removal of oxidants. Due to these properties, glutamine is considered an essential amino acid in diets for weaned piglets.