Uric acid synthesis by rat liver supernatants from purine bases, nucleosides and nucleotides. Effect of allopurinol (original) (raw)
Related papers
Life Sciences, 2002
Uric acid and allantoin are the key compounds of purine nucleotide catabolism formed in liver and many other organs of the rat. We observed that, after administration of 14 C-formate, incorporation of radioactivity into uric acid and allantoin is not similar, as one would expect. The phenomenon was demonstrated to be specific to liver and perfused liver, and not to other organs such as heart, jejunal mucosa, lung, spleen, and kidney. To interpret these results, the specific radioactivity of uric acid and allantoin in rat liver were analysed comparatively, after administration of the following labelled precursors: 14 C-glycine, 14 C-formate, 14 C-hypoxanthine, 14 C-uric acid and 14 C-adenine. After administration of 14 C-formate the specific radioactivity of allantoin was higher than that of uric acid and the same behavior was observed after 14 C-uric acid and 14 C-hypoxanthine, but not after 14 C-glycine and 14 C-adenine administration. The results indicate that the rate of their incorporation into uric acid and allantoin, and the subsequent export of these compounds into serum, can only partially explain the observed phenomenon, while the presence of different pools of uric acid and allantoin may give a complete explanation. D
De novo synthesis of uracil nucleotides in mouse liver and intestine studied using [15N]alanine
European Journal of Biochemistry, 1990
The amount of newly synthesized uracil nucleotides in mouse liver and intestine was determined by analysis of 15N incorporation into the uracil nucleotide pool of these tissues after intraperitoneal infusion of 15N-labelled amino acids. The appearance of newly synthesized uracil nucleotides was linear with time, and essentially independent of the rate of infusion of L-[15N]alanine. Varying the amino acid used in the infusion could affect the enrichment in the uracil ring nitrogens, but had no significant effect on the calculated amount of de novo synthesis. These results demonstrate the utility of this method in measuring de novo uracil nucleotide synthesis in mouse liver and intestine in vivo. The method should be a valuable tool in the effort to understand the regulation and pharmacological manipulation of de novo uracil nucleotide synthesis.
European Journal of Biochemistry, 1988
De novo pyrimidine synthesis was studied in mouse liver, intestine, and kidney by intraperitoneal infusion of 15NH4Cl and analysis of 15N incorporation into uracil nucleotide pools. When the dose of a 1-h infusion of 15NH4Cl was increased from 50 mumol to 250 mumol the fraction of the total uracil nucleotide pool formed by de novo synthesis increased 4.0-fold in liver to 8.4% and 2.3-fold in intestine to 13.7%. The increase in intestine was independent of the increase in liver as evidenced by the lack of correlation between the increase observed in the intestine and liver of the same animal and the different distributions of label in the uracil ring nitrogens. A 2.4-fold increase in newly formed uracil nucleotides was observed in kidney when the infusion dose was raised from 150 mumol to 250 mumol. The increase in kidney was correlated with the increase in liver in the same animal and the distribution of label in the uracil ring nitrogens was similar to the distribution in liver. These results suggest that the increase in newly formed uracil nucleotides in intestine is due to increased de novo synthesis of pyrimidines in the intestine, while the increase in the kidney is due to increased salvage synthesis of uracil nucleotides from uridine synthesized in the liver and output to the circulation.
2019
The uric acid alteration in human beings causes major health problem due to its pivotal role in the etiology of many systemic diseases. The purine metabolism enzyme activities have a significant role in the process of elevated uric acid in diabetes mellitus. Hence, a study has been undertaken to understand the alteration of these enzyme activities in diabetic condition with an attempt to establish the possible cause for uric acid elevation. Alloxan was administered (150 mg/kg; i.p.) to induce diabetes in rats. Thirty days after alloxan induced diabetes, the enzyme activities were assessed in both plasma and liver tissues. The enzyme activities such as 5-nucleotidase (5-NT), adenosine deaminase (ADA), xanthine oxidase (XO) in the plasma and liver tissues were assayed by spectrometric technique and uric acid levels were also measured by Caraway procedure. A significant (P< 0.001) increase in 5-NT, ADA and XO enzyme activities in plasma and liver tissue with a concomitant increase (P< 0.001) in uric acid levels was observed in diabetic group. The uric acid and the activities of enzymes did not change significantly in control group. From the present study, it can be concluded that an increase in uric acid levels noticed in diabetic condition may be due to increased catabolism of purines as evidenced by increased activities of 5-NT, ADA and XO enzymes.
Towards the physiological function of uric acid
Free Radical Biology and Medicine, 1993
Uric acid, or more correctly (at physiological pH values), its monoanion urate, is traditionally considered to be a metabolically inert end-product of purine metabolism in man, without any physiological value. However, this ubiquitous compound has proven to be a selective antioxidant, capable especially of reaction with hydroxyl radicals and hypochlorous acid, itself being converted to innocuous products (allantoin, allantoate, glyoxylate, urea, oxalate). There is now evidence for such processes not only in vitro and in isolated organs, but also in the human lung in vivo. Urate may also serve as an oxidisable cosubstrate for the enzyme cyclooxygenase. As shown for the coronary system, a major site of production of urate is the microvascular endothelium, and there is generally a net release ofurate from the human myocardium in vivo. In isolated organ preparations, urate protects against reperfusion damage induced by activated granulocytes, cells known to produce a variety of radicals and oxidants. Intriguingly, urate prevents oxidative inactivation of endothelial enzymes (cyclooxygenase, angiotensin converting enzyme) and preserves the ability of the endothelium to mediate vascular dilatation in the face of oxidative stress, suggesting a particular relationship between the site of urate formation and the need for a biologically potent radical scavenger and antioxidant.
Regulation of uric acid metabolism and excretion
International Journal of Cardiology, 2016
Purines perform many important functions in the cell, being the formation of the monomeric precursors of nucleic acids DNA and RNA the most relevant one. Purines which also contribute to modulate energy metabolism and signal transduction, are structural components of some coenzymes and have been shown to play important roles in the physiology of platelets, muscles and neurotransmission. All cells require a balanced quantity of purines for growth, proliferation and survival. Under physiological conditions the enzymes involved in the purine metabolism maintain in the cell a balanced ratio between their synthesis and degradation. In humans the final compound of purines catabolism is uric acid. All other mammals possess the enzyme uricase that converts uric acid to allantoin that is easily eliminated through urine. Overproduction of uric acid, generated from the metabolism of purines, has been proven to play emerging roles in human disease. In fact the increase of serum uric acid is inversely associated with disease severity and especially with cardiovascular disease states. This review describes the enzymatic pathways involved in the degradation of purines, getting into their structure and biochemistry until the uric acid formation.
Functionalities of Purines in Health and Disease
2019
Purines conduct several vital cellular functions as in the production of the numericprecursors of nucleic acids, whereas excess formation of uric acid generated from purines metabolism has been expansively implicated in human disease. The physiological functions and pathogenic attributes of uric acid have been linked to the imminent presentations of cardiovascular abnormalities, diabetes and stroke. Inasmuch as the overproduction of uric acid results in gout, it is established that uric acid constitutes a potent antioxidant in the shielding of DNA from single-strand breaks due to free radicals culminating in a protective effect in neurodegenerative disorders for an extended life span. Thus, this paper describes certain contronymic effects in the functionalities of purines in health and disease.
Purine catabolism in isolated rat hepatocytes. Influence of coformycin
The Biochemical journal, 1980
1. The catabolism of purine nucleotides was investigated by both chemical and radiochemical methods in isolated rat hepatocytes, previously incubated with [(14)C]adenine. The production of allantoin reached 32+/-5nmol/min per g of cells (mean+/-s.e.m.) and as much as 30% of the radioactivity incorporated in the adenine nucleotides was lost after 1h. This rate of degradation is severalfold in excess over values previously reported to occur in the liver in vivo. An explanation for this enhancement of catabolism may be the decrease in the concentration of GTP. 2. In a high-speed supernatant of rat liver, adenosine deaminase was maximally inhibited by 0.1mum-coformycin. The activity of AMP deaminase, measured in the presence of its stimulator ATP in the same preparation, as well as the activity of the partially purified enzyme, measured after addition of its physiological inhibitors GTP and Pi, required 50mum-coformycin for maximal inhibition. 3. The production of allantoin by isolated ...