Gout
Charles Theisler in Adjuvant Medical Care, 2023
Gout, or acute gouty arthritis, typically presents as an excruciating attack of pain, usually in a single joint of the foot or ankle. Gout is the most common inflammatory arthritis of men and is increasing in prevalence.1 Gout is associated with an overproduction (10% of patients) or decreased renal excretion (90% of patients) of purines. Because the end product of purine metabolism is uric acid, gout is characterized by elevated blood uric acid levels.2 Needle-like uric acid crystals form in joint spaces resulting in episodes of sudden excruciating pain, swelling, redness, warmth, and tenderness. Chronic inflammation and clumps of crystals (tophi) can lead to permanent joint damage, deformity, and stiffness. Tophi can also form in white chalky nodules on the helix of the ear. These tophi typically become painful before or during gout attacks.
Osteoarthritis
Nicole M. Farmer, Andres Victor Ardisson Korat in Cooking for Health and Disease Prevention, 2022
Dietary patterns to be aware of for OA symptom management may also relate to development, not just prevention, of OA. Based on the pathophysiology evidence presented earlier, adverse dietary patterns may include high glycemic diets and diets that promote production of uric acid. Dietary factors related to uric acid exposure actually overlap with dietary patterns related to hyperglycemia. Added sugars that provide fructose either from sugar sweetened or naturally occurring fructose from fruit juices are linked to higher risk of uric acid formation and gout. Additionally, consumption of purine-rich animal foods, but not purine-rich vegetables, is linked to increased risk for gout. This suggests an adverse role for foods that contain stearic acid such as lard and tallow when present in a diet or meal that may lead to uric acid synthesis.
The Role of the Clinical Laboratory in Nutritional Assessment
Aruna Bakhru in Nutrition and Integrative Medicine, 2018
Calcium oxalate kidney stones are the leading type of kidney stones. Oxalate is naturally found in many foods, including fruits and vegetables, nuts and seeds, grains, legumes, and even chocolate and tea. Some examples of foods that contain high levels of oxalate include peanuts, rhubarb, spinach, beets, chocolate, and sweet potatoes. Another common type of kidney stone is a uric acid stone. Red meat and shellfish have high concentrations of a natural chemical compound known as a purine. High purine intake leads to a higher production of uric acid, which then accumulates as crystals in the joints or as stones in the kidneys. Again, based on the type of kidney stone, different diets and medication are prescribed. Monitoring 24-hour urine is often used in patient management to reduce reoccurrence.52
Identification of a new structural family of SGK1 inhibitors as potential neuroprotective agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Ines Maestro, Enrique Madruga, Patricia Boya, Ana Martínez
It was interesting to see the lack of inhibitory activity of the purine derivatives, probably caused by the tautomerism between both nitrogen atoms of the imidazole ring. As we mentioned before, the hydrogen bond interaction between the NH from the heterocyclic scaffold and Arg177 is key for SGK1 inhibition. Thus, in the purine moiety the hydrogen atom can moved between the two nitrogen atoms of the five membered ring. With the software MarvinSketch (version 18.10.0, ChemAxon Ltd.) we could determine that at physiological pH the most abundant species of ERP1.22 is number 1 (Figure 7), the neutral state Using the same software, we calculated the relative abundance of each tautomer for this state. Surprisingly, only the 86% of the population corresponds to the tautomer that is able to interact properly with the hinge region, while the rest of specieslack the hydrogen needed to form the hydrogen bond with Asp177 in the catalytic site. This may decrease the interaction with the two key amino acids within the catalytic site, which translates in the lack of inhibitory potency. Furthermore, in terms of binding energy, desolvation energy plays a critical role in protein-ligand interaction. As the scaffold needs to be almost completely desolvated to reach the hydrophobic binding site, it is very likely that the deazapurine moiety is energetically more favourable to accomplish this in comparison to the purine scaffold. However, further calculations are needed to confirm this.
Genetic and Epigenetic Regulation of the Innate Immune Response to Gout
Published in Immunological Investigations, 2023
Jordana Dinorá de Lima, André Guilherme Portela de Paula, Bruna Sadae Yuasa, Caio Cesar de Souza Smanioto, Maria Clara da Cruz Silva, Priscila Ianzen dos Santos, Karin Braun Prado, Angelica Beate Winter Boldt, Tárcio Teodoro Braga
Hyperuricemia is the main clinical parameter in gout diagnosis. There are three main causes of hyperuricemia. The first is disorders at purine synthesis through de novo and salvage pathways (essential for replacing damaged nitrogen bases and producing ATP and cyclic AMP (cAMP)), which ultimately leads to urate crystallization and accumulation (Huang et al. 2021). The second is high purine ingestion, mainly through meat, and seafood, which adds excessive purine from external dietary sources (Choi et al. 2005). Similarly, fructose and alcohol-rich diets lead to an AMP excess, which causes inosine monophosphate (IMP) accumulation, one of the uric acid precursors (Huang et al. 2021). Third, purine excretion defects may increase UA. Despite being converted by uricase into allantoin in most animals, UA excretion is hampered in humans, which lost this enzyme during the evolutionary process (Zhu et al. 2018).
Interactions of 2,6-substituted purines with purine nucleoside phosphorylase from Helicobacter pylori in solution and in the crystal, and the effects of these compounds on cell cultures of this bacterium
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Marta Narczyk, Marta Ilona Wojtyś, Ivana Leščić Ašler, Biserka Žinić, Marija Luić, Elżbieta Katarzyna Jagusztyn-Krynicka, Zoran Štefanić, Agnieszka Bzowska
Enzymes belonging to the purine salvage pathway are possible targets of such new drugs because numerous microorganisms, including infectious pathogenic species, are unable to synthesise de novo purine nucleotides11–16. Therefore, the recovery of purines and purine nucleotides from the environment is for them the only source of these essential DNA and RNA building blocks. Given the importance of purine production and its direct effect on the organisms growth rate, targeting enzymes of the purine salvage pathway became a promising approach to find new drugs against such pathogens. One promising example of the new drug candidate is DADMe-Immucillin-G, a transition state inhibitor of the key enzyme of the purine salvage pathway, purine nucleoside phosphorylase (PNP), which shows clinical potential for treatment of the malaria parasite Plasmodium falciparum16.