Uric Acid: Chemistry and Synthesis

The present experiment was camed out to study the endogenous losses of purine and pyrimidine derivatives from pregnant sows. Three pregnant and three non-pregnant Large White x Landrace sows were fed on a purine-free diet composed of starch, glucose, sucrose and vegetable oil, with casein as the protein source. The experiment began, for the six animals, after diagnosis of pregnancy and was divided into six 12 d periods. Urine was collected during the Arst 3 d of each experimental period by means of a urethral catheter for determination of allantoin, uric acid, xanthine, hypoxanthine and pseudouridine concentrations. In the absence of dietary nucleic acids (NA), allantoin and, as a consequence, excretion of total purine derivatives (PD) decreased significantly to a constant value (128.3 (SE 7.07) ,umol/kg metabolic live weight (W"75) per d), an amount assumed to represent endogenous excretion. Excretion of uric acid (38.7 (SE 2-15) mollkg W0'75 per d), hypoxanthine (21.0 (SE 2.58) ymollkg W ' 7 5 per d) and xanthine (11-2 (SE 0.83) pmol/kg W@" per d) were not affected by the experimental treatment, although there was a significant decrease in hypoxanthine excretion in pregnant sows (from 25.5 to 5.2 pnol/kg W@75 per d) compared with nowpregnant sows (from 26.7 to 44%/rmol/kg W@75 per d). Creatinine excretion was not affected by pregnancy and was used as an internal urinary marker. Purine excretion, either expressed as pmol/kg WoT5 per d or as the ratio PD:creatinine, was not affected by experimental treatment, although an apparent increase in pseudouridine excretion, a modified unsalvageable catabolite of RNA-pyrimidine, was found in late pregnancy (3.6 v. 5.2 mo1/100 mol creatinine in non-pregnant sows compared with pregnant sows at 102 d collection).Purine derivatives : Pseudouridine : Pregnancy : Sow Metabolism of nucleic acids (NA) involves a substrate cycle whereby nucleotides are degraded continuously to nucleosides and free bases which are subsequently salvaged for re-synthesis of new nucleotides (Murray, 1971). However, this NA turnover is not fully efficient, generating, as a consequence, endogenous losses which constitute an important fraction of the total urinary excretion of purine derivatives (PD). These endogenous losses, measured as urinary PD excretion when there is no exogenous NA supply, have been measured in single-stomached animals fed on purine-free diets (Greife, 1980;Chen et al. 1990b), in preruminants maintained on a purine-free liquid diet (Lindberg, 1991) and in ruminants, either by avoiding rumen fermentation (Orskov et al. 1979;Chen et al. 1990b) or by substituting duodenal flow for a purine-free solution (Balcells et al. 1991).In previous reports, changes in nutritional status, i.e. protein (Fujihara et al. 1987) or energy supply (Giesecke et al. 1984; Lindberg & Jacobson, 1990), had little effect on endogenous excretion of PD. However, there is a lack of information about the variations in endogenous losses in relation to different physiological states, and how these variations must ...

Section: Endogenous Excretion Of Purine Derivativessupporting

confidence: 87%

Endogenous purine and pyrimidine derivative excretion in pregnant sows

Orúe

Balcells²,

Guada³

et al. 1995

“…Exogenous purines are absorbed from the intestines as purine nucleosides and free bases (Wilson & Wilson, 1962). If they are not converted into xanthine, uric acid and allantoin on their passage across the intestinal wall, they will be available for incorporation into tissue nucleic acids through the purine salvage pathway (xanthine can be salvaged, but only at a very low rate; Hitchings, 1978). Unlike cattle, sheep intestinal mucosa has only trace xanthine oxidase (EC I .2.3.2) activity (Al-Khalidi & Chaglassian, 1965), therefore conversion of exogenous purines into the non-salvageable derivatives should not be quantitatively significant.…”

Section: Utilization Of Exogenous Purinesmentioning

confidence: 99%

Excretion of purine derivatives by ruminants: effect of exogenous nucleic acid supply on purine derivative excretion by sheep

Chen¹,

Hovell²,

Ørskov³

et al. 1990

253

180

The present study examined the relationship between the supply of exogenous nucleic acid (NA) purines and their recovery as the derivatives hypoxanthine, xanthine, uric acid and allantoin in urine. Six lambs, totally nourished by intragastric infusions of volatile fatty acids (VFA) and casein (i.e. no rumen fermentation), were given by abomasal infusion a microbial NA concentrate at six levels (from zero to 24.5 mmol purines/d). The true digestibility between the abomasum and terminal ileum of the NA purines was measured in a separate experiment using three lambs. The relative proportion of urinary allantoin increased, and that of other derivatives decreased, as the amount of NA infused was increased. The relationship between total excretion of purine derivatives ( Y; mmol/d) and exogenous purines absorbed (X, mmol/d) was Y = 0~84X+0~150W0~7see-0~25x, where W is body-weight (kg). This implies that the endogenous contribution to the total excretion of derivative decreased as the supply of exogenous purines increased, with an associated progressive replacement of de n o w synthesis by exogenous purines. The model also implies that 0.16 of the purines were eliminated through routes other than derivative excretion in urine. Once excretion exceeded 0.6 mmol/kg WO." per d, endogenous excretion was effectively zero and thus Y = 084 X. In normally fed sheep, derivative excretion should therefore relate to the microbial purines and, hence, microbial protein absorbed according to these models. The changing proportions of allantoin and other derivatives in urine were probably due to changes in the relative importance of endogenous and exogenous purines as precursors. Nucleic acids: Purine derivatives: SheepStudies on the urinary excretion of purine derivatives by ruminants have been stimulated by the possible use of their excretion as an estimator of the rumen microbial protein supplied to the host animal. This is because in ruminants nucleic acids (NA) flowing to the small intestines are essentially of rumen microbial origin (McAHan & Smith, 1973). Absorbed purines are degraded to hypoxanthine, xanthine, uric acid and allantoin, which are excreted in urine, and should relate quantitatively to the amount of purines and, hence, microbial protein absorbed.The excretion of allantoin has been shown to be correlated with the amount of NA infused post ruminally to sheep (Antoniewicz et al. 1980;Sibanda et al. 1982;Giesecke et al. 1984;Lindberg, 1985;Fujihara et al. 1987). However, recoveries of NA-nitrogen as allantoin-N reported by these authors varied from 0.12 to 0.47 (i.e. purine recoveries of 0.22-0.79). Since uric acid, xanthine and hypoxanthine were not measured, it is not possible to assess whether the recovery of absorbed purines as the derivatives in the urine was complete in these studies. It is also not clear from the existing information whether, and to what extent, exogenous purines would be retained by the animal body.In the studies to be reported here the intragastric infusion technique (0rskov et al. 1979) was e...

“…Xanthine oxidase diverts hypoxanthine away from this cycle to form xanthine and uric acid which can be subsequently oxidized in the presence of uricase to form allantoin. Uric acid and allantoin are not salvageable, and although xanthine may be salvaged by hypoxanthineguanine phosphoribosyltransferase to form xanthosine monophosphate (Gots, 1971), this reaction is slow due to the low affinity for xanthine by the enzyme (Hitchings, 1978). Therefore, xanthine oxidase is probably the key enzyme which defines the loss of purine derivatives in the urine.…”

Section: Possible Link Between the Xanthine Oxidase Activity And The mentioning

confidence: 99%

Excretion of purine derivatives by ruminants: endogenous excretion, differences between cattle and sheep

Chen¹,

Ørskov²,

Hovell³

1990

131

The endogenous urinary excretion of the purine derivatives allantoin, uric acid and xanthine plus hypoxanthine were measured in twenty-nine lambs, ten cattle (six steers, one cow and three preruminant calves) and four pigs. The sheep and mature cattle were nourished by intragastric infusion and the calves were given a milk-substitute. The pigs were fed on a purine-free diet. The excretion of total purine derivatives was substantially greater by the cattle, being 514 (SE 20.6) pmol/kg live weight (W)'" per d compared with 168 (SE 5.0) pmol/kg Wo7' per d by the sheep and 166 (SE 2.6) pmol/kg WO" per d by the pigs. Plasma from normally fed sheep, cows and pigs was incubated with either xanthine or uric acid. Sheep and pig plasma had no xanthine oxidase (EC 1.2.3.2) activity whereas plasma from cattle did. Uricase (EC 1 .7.3.3) was not present in plasma of cattle and pigs and appeared to be present in trace amounts only in sheep plasma. It is suggested that the species differences in endogenous purine derivative excretion were probably due to the different profiles of xanthine oxidase activity in tissues and particularly in the blood. This is because a high xanthine oxidase activity would reduce the chance to recycle purines, by increasing the probability of degradation to compounds which could not be salvaged.