The disorders of purine and pyrimidine metabolism are unusual in their variety of clinical presentations and in the mechanisms by which these presentations result from the fundamental mutations. In the most common of the hyperuricemic metabolic disorders, deficiency of hypoxanthine phosphoribosyl transferase, the fundamental deficiency in the activity of an enzyme of purine salvage leads to enormous overactivity of de novo pathway of purine synthesis and purine overproduction. In the other hyperuricemic disorder, that of phosphoribosylpyrophosphate synthetase, mutation leads not to deficient activity, but superactivity of the enzyme in an early stage of the synthetic pathway leading to overproduction. A number of disorders of purine metabolism lead to immunodeficiency; these include adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency. Marked susceptibility to infection is also seen in disorders of pyrimidine metabolism, classically in orotic aciduria, but also in pyrimidine nucleotide depletion syndrome. Orotic aciduria is a disorder of pyrimidine nucleotide synthesis, UMP synthetase deficiency, in which a single gene mutation can cause deficiency of two enzyme activities, orotic phosphoribosyltransferase and orotidine monophosphate decarboxylase which reside in a single protein. Pyrimidine degradation defects, dihydropyrimidine dehydrogenase and dihydropyrimidinase deficiencies leading to developmental delay are detected by analysis of the urine for pyrimidines and dihydropyrimidines. The recent discovery of aminoimidazolecarboxamideriboside deficiency points up the utility of simple colorimetric tests in bringing to light disorders of metabolism. Adenylosuccinatelyase deficiency and molybdenum cofactor deficiency illustrate the same point.
"Despite the adaptations to diving and the physiological adjustments during diving, when oxygen reserves are depleted, blood and tissues become hypoxic and ATP hydrolysis results in the accumulation of xanthine and uric acid, purine metabolites which can not be recycled (Janssen, 1993; Elsner, 1999). An alternative mechanism for maintenance of the purine nucleotide pool is the salvage pathway, which conserves energy and uses preformed bases from degradation of nucleic acids and from the diet (Alexiou and Leese, 1992; Carver, 1999; Moriwaki et al., 1999; Nyhan, 2005; Zhang et al., 2008). Nucleotides such as inosine 5 ′ -monophosphate (IMP), guanosine 5 ′ -monophosphate (GMP), and adenosine 5 ′ -monophosphate (AMP) can be regenerated by this pathway (Carver, 1999; Zhang et al., 2008). "
[Show abstract][Hide abstract] ABSTRACT: Aquatic and semiaquatic mammals have the capacity of breath hold (apnea) diving. Northern elephant seals (Mirounga angustirostris) have the ability to perform deep and long duration dives; during a routine dive, adults can hold their breath for 25min. Neotropical river otters (Lontra longicaudis annectens) can hold their breath for about 30 s. Such periods of apnea may result in reduced oxygen concentration (hypoxia) and reduced blood supply (ischemia) to tissues. Production of adenosine 5′-triphosphate (ATP) requires oxygen, and most mammalian species, like the domestic pig (Sus scrofa), are not adapted to tolerate hypoxia and ischemia, conditions that result in ATP degradation. The objective of this study was to explore the differences in purine synthesis and recycling in erythrocytes and plasma of three mammalian species adapted to different environments: aquatic (northern elephant seal) (n = 11), semiaquatic (neotropical river otter) (n = 4), and terrestrial (domestic pig) (n = 11). Enzymatic activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) was determined by spectrophotometry, and activity of inosine 5′-monophosphate dehydrogenase (IMPDH) and the concentration of hypoxanthine (HX), inosine 5′-monophosphate (IMP), adenosine 5′-monophosphate (AMP), adenosine 5′-diphosphate (ADP), ATP, guanosine 5′-diphosphate (GDP), guanosine 5′-triphosphate (GTP), and xanthosine 5′-monophosphate (XMP) were determined by high-performance liquid chromatography (HPLC).TheactivitiesofHGPRTandIMPDHandtheconcentrationofHX,IMP,AMP,ADP, ATP, GTP, and XMP in erythrocytes of domestic pigs were higher than in erythrocytes of northern elephant seals and river otters. These results suggest that under basal conditions (no diving, sleep apnea or exercise), aquatic, and semiaquatic mammals have less purine mobilization than their terrestrial counterparts.
Frontiers in Physiology 07/2015; 6. DOI:10.3389/fphys.2015.00212 · 3.53 Impact Factor
"There also are intercellular signaling pathways involving adenine or guanine metabolites , and G-proteins that require cAMP or cGMP. The importance of purines for normal brain function is highlighted by several rare inherited disorders of purine metabolism    . For example , defects in purine recycling mediated by the enzyme hypoxanthine–guanine phosphoribosyltransferase (HGprt) cause the severe neurobehavioral problems of Lesch–Nyhan disease (LND). "
"Pyrimidine metabolism, along with purine pathway, fulfill a variety of functions in the metabolism of the cell, of which the most important are, regulation of energy conservation and transport, formation of coenzymes and active intermediation in phospholipid and carbohydrate metabolism (GENNIP, 1999). Nyhan postulated that the catabolic pathways for pyrimidine have caused specific enzymatic deficiencies in a number of patients, most of them with mental retardation, seizures, or both (Nyhan, 2005). Degradation disorders of pyrimidine can be presented as anemia, neurological deficits, or devastating multisystem mitochondrial disorder (Anne Simmonds and Gennip, 2003). "
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