RESUMEN
Xanthinuria is a rare autosomal recessive disorder associated with a deficiency of xanthine oxidoreductase (XOR), which normally catalyzes the conversion of hypoxanthine to uric acid. The effects of this deficit are an elevated concentration of hypoxanthine and xanthine in the blood and urine, hypouricemia, and hypouricuria. The deficit in XOR can be isolated (type I xanthinuria) or associated with a deficit in aldehyde oxidase (type II xanthinuria) and sulfite oxidase (type III xanthinuria). While the first two variants have a benign course, are often asymptomatic (20%), and clinically indistinguishable, type III xanthinuria is a harmful form that leads to infant death due to neurological damage. The clinical symptoms (kidney stones, CKD, muscle and joint pain, peptic ulcer) are the result of the accumulation of xanthine, which is highly insoluble, in the body fluids. We describe a case of type I xanthinuria in a 52-year-old woman who presented with hypouricemia, hypouricuria and kidney stones. The diagnosis was based on purine catabolite levels in urine and serum measured by 3 nonroutine methods: high-pressure liquid chromatography, mass spectrometry, and magnetic resonance imaging. To identify the type of xanthinuria the allopurinol test was used. We believe that these tests will facilitate the diagnosis of xantinuria especially in asymptomatic patients without the need for a biopsy of the liver or intestines, which is useful only for scientific purposes.
Asunto(s)
Hipoxantinas , Errores Innatos del Metabolismo de la Purina-Pirimidina/complicaciones , Errores Innatos del Metabolismo de la Purina-Pirimidina/diagnóstico , Ácido Úrico , Xantina/orina , Alopurinol/orina , Biomarcadores/sangre , Biomarcadores/orina , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Hipertensión/etiología , Hipoxantinas/sangre , Hipoxantinas/orina , Imagen por Resonancia Magnética , Espectrometría de Masas , Persona de Mediana Edad , Nefrolitiasis/etiología , Valor Predictivo de las Pruebas , Errores Innatos del Metabolismo de la Purina-Pirimidina/sangre , Errores Innatos del Metabolismo de la Purina-Pirimidina/dietoterapia , Errores Innatos del Metabolismo de la Purina-Pirimidina/orina , Sensibilidad y Especificidad , Resultado del Tratamiento , Ácido Úrico/sangre , Ácido Úrico/orina , Xantina/sangreRESUMEN
To investigate the effects of exercise on the plasma concentrations and urinary excretion of purine bases and oxypurinol, we performed 3 experiments with 6 healthy male subjects. The first was a combination of allopurinol intake (300 mg) and exercise (VO2max, 70%) (combination experiment), the second was exercise alone (exercise-alone experiment), and the third was allopurinol intake alone (allopurinol-alone experiment). In the combination experiment, exercise increased the concentrations of purine bases and noradrenaline in plasma, as well as lactic acid in blood and the urinary excretion of oxypurines, whereas it decreased the urinary excretion of uric acid and oxypurinol as well as the fractional excretion of hypoxanthine, xanthine, uric acid, and oxypurinol. In the exercise-alone experiment, exercise increased the concentrations of purine bases and noradrenaline in plasma, lactic acid in blood, and the urinary excretion of oxypurines, whereas it decreased the urinary excretion of uric acid and fractional excretion of purine bases. In contrast, in the allopurinol-alone experiment, the plasma concentration, urinary excretion, and fractional excretion of purine bases and oxypurinol remained unchanged. These results suggest that increases in adenine nucleotide degradation and lactic acid production, as well as a release of noradrenaline caused by exercise, contribute to increases in plasma concentration and urinary excretion of oxypurines and plasma concentration of urate, as well as decreases in urinary excretion of uric acid and oxypurinol, along with fractional excretion of uric acid, oxypurinol, and xanthine. In addition, they suggest that oxypurinol does not significantly inhibit the exercise-induced increase in plasma concentration of urate.
Asunto(s)
Ejercicio Físico/fisiología , Oxipurinol/sangre , Oxipurinol/orina , Purinas/sangre , Purinas/orina , Adulto , Creatinina/metabolismo , Humanos , Hipoxantinas/sangre , Hipoxantinas/orina , Ácido Láctico/sangre , Masculino , Norepinefrina/sangre , Ácido Úrico/sangre , Ácido Úrico/orina , Xantinas/sangre , Xantinas/orinaRESUMEN
A capillary electrophoretic (CE) method for the determination of hypoxanthine and xanthine in urine was developed to diagnose xanthinuria. The linearity was excellent up to 200 mumol l-1 for the two compounds and the limit of quantitation was 2 mumol l-1. A comparison o the results obtained using CE was made with those obtained by the high-performance liquid chromatographic (HPLC) technique described previously. With regard to specificity, sensitivity and reproducibility, the results are similar but CE is more rapid than HPLC.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Electroforesis Capilar/métodos , Hipoxantinas/orina , Errores Innatos del Metabolismo de la Purina-Pirimidina/diagnóstico , Xantinas/orina , Cromatografía Líquida de Alta Presión/estadística & datos numéricos , Electroforesis Capilar/estadística & datos numéricos , Humanos , Hipoxantina , Errores Innatos del Metabolismo de la Purina-Pirimidina/orina , XantinaRESUMEN
We report a high-performance liquid chromatographic method with column switching for urinary hypoxanthine and xanthine. Analyses were carried out with both a reversed-phase column and an anion-exchange column connected by a column switch and controlled automatically by a computerized system controller. The relationships between standard concentrations and peak heights were linear in a concentration range of 1 to 1000 nmol/ml. The recovery of hypoxanthine added to urine was 101.1%, and that of xanthine was 98.1%. With our method urinary hypoxanthine and xanthine can be measured accurately without any sample preparation other than filtration.
Asunto(s)
Hipoxantinas/orina , Xantinas/orina , Adulto , Autoanálisis , Cromatografía Líquida de Alta Presión , Humanos , Valores de Referencia , Espectrofotometría UltravioletaRESUMEN
We investigated the effect of xylitol on the plasma concentration and the urinary excretion of purine bases, 5-hydroxypyrazinamide and 5-hydroxypyrazinoic acid in subjects who had ingested pyrazinamide (60 mg/kg weight). One liter of 10% xylitol was infused intravenously over 2 hours to 5 subjects to whom pyrazinamide had been administered 10 hours before. Xylitol increased the plasma concentration of uric acid, hypoxanthine and xanthine, the urinary excretion of hypoxanthine and a ratio of lactic acid/pyruvic acid in blood, while it decreased the plasma concentration and the urinary excretion of inorganic phosphate, 5-hydroxypyrazinamide and 5-hydroxypyrazinoic acid. These results suggested that in addition to an increase in purine degradation by xylitol, xylitol-induced increase in the cytosolic NADH inhibited xanthine dehydrogenase activity in the liver and the small intestine.
Asunto(s)
Pirazinamida/análogos & derivados , Xilitol/farmacología , Administración Oral , Adulto , Cromatografía Líquida de Alta Presión , Citosol/metabolismo , Humanos , Hipoxantina , Hipoxantinas/sangre , Hipoxantinas/orina , Infusiones Intravenosas , Inosina/administración & dosificación , Inosina/farmacología , Intestino Delgado/efectos de los fármacos , Intestino Delgado/enzimología , Lactatos/sangre , Ácido Láctico , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Persona de Mediana Edad , NAD/farmacología , Fosfatos/sangre , Pirazinamida/administración & dosificación , Pirazinamida/sangre , Pirazinamida/orina , Piruvatos/sangre , Ácido Pirúvico , Solución Salina Hipertónica/administración & dosificación , Albúmina Sérica/análisis , Ácido Úrico/sangre , Ácido Úrico/orina , Xantina , Xantina Deshidrogenasa/antagonistas & inhibidores , Xantina Deshidrogenasa/metabolismo , Xantinas/sangre , Xantinas/orina , Xilitol/administración & dosificación , Xilitol/sangreRESUMEN
We investigated the effect of glucose infusion on adenosine triphosphate degradation in skeletal muscle of patients with glycogen storage disease type VII. Three patients and six healthy subjects exercised on a bicycle ergometer twice, once with 20% glucose infusion and once with saline infusion. The glucose infusion increased plasma glucose levels to 170 to 182 mg/dl and serum insulin levels to 30 to 50 microU/ml, while it markedly decreased plasma free fatty acid levels. The exercise-induced increases in plasma ammonia, inosine, and hypoxanthine were much larger with glucose than with saline infusion in the patients. Urinary excretion of inosine and hypoxanthine with glucose infusion was twice as high as that with saline infusion. No such differences were present between glucose and saline infusion in the healthy subjects. Glucose infusion therefore accelerates the energy crisis in working muscle of patients with glycogen storage disease type VII, probably due to a decrease in fatty acid utilization.
Asunto(s)
Nucleótidos de Adenina/metabolismo , Glucosa/farmacología , Enfermedad del Almacenamiento de Glucógeno Tipo VII/metabolismo , Músculo Esquelético/metabolismo , Adulto , Amoníaco/sangre , Glucemia/metabolismo , Prueba de Esfuerzo , Ácidos Grasos no Esterificados/sangre , Femenino , Glucosa/administración & dosificación , Enfermedad del Almacenamiento de Glucógeno Tipo VII/fisiopatología , Humanos , Hipoxantina , Hipoxantinas/sangre , Hipoxantinas/orina , Inosina/sangre , Inosina/orina , Insulina/sangre , Masculino , Músculo Esquelético/fisiología , Músculo Esquelético/fisiopatología , Esfuerzo Físico , Valores de Referencia , Factores de TiempoRESUMEN
We examined the influence of alcohol drinking habits on the serum uric acid level after the ingestion of a small amount of ethanol. Subjects were divided into two groups according to their alcohol drinking habits--regular drinkers, who consume more than 60 g ethanol every day, and nondrinkers/occasional drinkers, who consume less than 20 g ethanol occasionally. Drinking 0.5 g ethanol/kg increased serum uric acid levels in regular drinkers by 52.6 +/- 26.3 mumol/L (0.8 +/- 0.4 mg/dL), whereas it did not in nondrinkers/occasional drinkers. Urinary excretion of uric acid was unaltered in both groups. Hypoxanthine and xanthine in both plasma and urine and serum acetate were increased more in regular drinkers than in nondrinkers/occasional drinkers. Accelerated adenine nucleotide degradation secondary to enhanced ethanol oxidation likely explains the ethanol-induced hyperuricemia in regular drinkers.
Asunto(s)
Consumo de Bebidas Alcohólicas/fisiopatología , Ácido Úrico/sangre , Acetatos/sangre , Adulto , Humanos , Hipoxantina , Hipoxantinas/sangre , Hipoxantinas/orina , Lactatos/sangre , Masculino , Factores de Tiempo , Xantina , Xantinas/sangre , Xantinas/orinaAsunto(s)
Eritrocitos/metabolismo , Errores Innatos del Metabolismo de la Purina-Pirimidina/enzimología , Ribonucleótidos/sangre , Ribosa-Fosfato Pirofosfoquinasa/metabolismo , Nucleótidos de Adenina/sangre , Alopurinol , Niño , Femenino , Nucleótidos de Guanina/sangre , Humanos , Hipoxantina , Hipoxantinas/sangre , Hipoxantinas/orina , Inosina/sangre , Masculino , NAD/sangre , Núcleo Familiar , Errores Innatos del Metabolismo de la Purina-Pirimidina/tratamiento farmacológico , Errores Innatos del Metabolismo de la Purina-Pirimidina/metabolismo , Valores de Referencia , Ribosa-Fosfato Pirofosfoquinasa/sangre , Ribosa-Fosfato Pirofosfoquinasa/orina , Ácido Úrico/sangre , Ácido Úrico/orina , Uridina/sangre , Uridina Difosfato Glucosa/sangre , Xantina , Xantinas/sangre , Xantinas/orinaAsunto(s)
Aminoimidazol Carboxamida/análogos & derivados , Síndrome de Lesch-Nyhan/tratamiento farmacológico , Ribonucleótidos/uso terapéutico , Adolescente , Aminoimidazol Carboxamida/administración & dosificación , Aminoimidazol Carboxamida/farmacocinética , Aminoimidazol Carboxamida/uso terapéutico , Humanos , Hipoxantina , Hipoxantinas/sangre , Hipoxantinas/orina , Infusiones Intravenosas , Síndrome de Lesch-Nyhan/complicaciones , Síndrome de Lesch-Nyhan/metabolismo , Leucemia/complicaciones , Leucemia/metabolismo , Masculino , Oxipurinol/orina , Ribonucleótidos/administración & dosificación , Ribonucleótidos/farmacocinética , Ácido Úrico/sangre , Ácido Úrico/orina , Xantina , Xantinas/sangre , Xantinas/orinaAsunto(s)
Hipoxantina Fosforribosiltransferasa/metabolismo , Síndrome de Lesch-Nyhan/sangre , Síndrome de Lesch-Nyhan/tratamiento farmacológico , Purinas/sangre , Niño , Eritrocitos/enzimología , Fibroblastos/enzimología , Humanos , Hipoxantina , Hipoxantina Fosforribosiltransferasa/sangre , Hipoxantinas/sangre , Hipoxantinas/orina , Síndrome de Lesch-Nyhan/orina , Masculino , Purinas/orina , Ácido Úrico/sangre , Ácido Úrico/orina , Xantina , Xantinas/sangre , Xantinas/orinaRESUMEN
Alcoholic ingestion is one of the major factors for increasing serum uric acid levels. Genotypes of aldehyde dehydrogenase 2 (ALDH2, E.C.1.2.1.3), which regulates the sensitivity of an individual to ethanol, were determined in Japanese patients with gout and control subjects by allele specific oligonucleotide hybridization using PCR amplified gene. The most common allele ALDH2*1 codes for normal ALDH2 activity, while the less common allele ALDH2*2 codes for a lower enzyme activity. The frequency of homozygotes of ALDH2*2 was significantly lower in patients with gout than those with rheumatoid arthritis or a normal population. Plasma and urinary hypoxanthine levels were strikingly increased after ethanol drinking in homozygotes for ALDH2*1 but not in heterozygotes for ALDH2*1/ALDH2*2, indicated extensive purine nucleotide degradation in homozygote for ALDH2*1. These data indicated that alcohol ingestion may not be the requisite factor but is deeply involved in the pathogenesis of gout and hyperuricemia.
Asunto(s)
Consumo de Bebidas Alcohólicas/sangre , Aldehído Deshidrogenasa/genética , Gota/enzimología , Gota/genética , Alelos , Tamización de Portadores Genéticos , Gota/metabolismo , Homocigoto , Humanos , Hipoxantina , Hipoxantinas/sangre , Hipoxantinas/orina , Isoenzimas/genética , Japón , Masculino , Valores de Referencia , Ácido Úrico/sangreRESUMEN
To investigate whether or not DL-sodium lactate inhibits the renal excretion of purine bases and oxypurinol, we administered physiological saline containing 0.2 mol DL-sodium lactate to 7 normal subjects intravenously. DL-sodium lactate infusion decreased the urinary excretion and the fractional clearance of uric acid, xanthine and oxypurinol, but the fractional clearance of hypoxanthine was not affected. These results suggested that the implications of DL-sodium lactate-induced hyperuricemia must be considered in patients with gout on its long term and high dose administration, and that the implications of DL-sodium lactate-induced prolongation of half-life of oxypurinol must be considered in hyperuricemic patients treated with allopurinol. However, since the high dose and long term administration of DL-sodium lactate is clinically rare, the effect of DL-sodium lactate infusion on the urinary excretion of uric acid, xanthine and oxypurinol may not be clinically important.
Asunto(s)
Lactatos/farmacología , Oxipurinol/orina , Purinas/orina , Adulto , Alopurinol/farmacología , Humanos , Hipoxantina , Hipoxantinas/orina , Lactatos/sangre , Ácido Láctico , Masculino , Albúmina Sérica/análisis , Ácido Úrico/orina , Xantina , Xantinas/orinaRESUMEN
Effects of exercise on the formation of 8-hydroxydeoxyguanosine (8-OH-dG), a biomarker of oxidative DNA damage, and other purine metabolites such as hypoxanthine, xanthine and uric acid were examined. Venous blood and urine were collected from swimmers and distance runners before and after the usual training. The amount of 8-OH-dG obtained from nuclear DNA of lymphocytes decreased remarkably after intermittent swimming. The amount of nuclear 8-OH-dG also declined after distance running, but this difference is statistically not significant. After each exercise, plasma concentrations of hypoxanthine, xanthine and uric acid rose significantly. Urinary excretion of hypoxanthine increased, and xanthine and uric acid decreased after exercise. The 8-OH-dG-to-creatinine ratio in urine increased slightly after swimming or running. It is supposed that the repair of oxidative DNA damage is augmented by exercise. As far as we know, this is the first report concerning the effect of exercise on oxidative damage in nuclear DNA.
Asunto(s)
Daño del ADN , ADN/química , Desoxiguanosina/análogos & derivados , Linfocitos/química , Carrera/fisiología , Natación/fisiología , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Creatinina/sangre , Creatinina/orina , ADN/orina , Desoxiguanosina/análisis , Desoxiguanosina/orina , Hematócrito , Humanos , Hipoxantina , Hipoxantinas/orina , Oxidación-Reducción , Ácido Úrico/orina , Xantina , Xantinas/orinaRESUMEN
Three patients with primary myoadenylate deaminase deficiency were subjected to exercise on a bicycle ergometer at 125 W for 30 minutes. Blood samples prior to, during, and at the end of exercise were analyzed for lactate, ammonia, and hypoxanthine. In addition, urinary hypoxanthine excretion was measured. In these patients the serum lactate level increased to concentrations between 7.9 and 9.0 mmol/l at the end of exercise whereas the mean lactate level in nine control subjects at the end of exercise was 3.3 mmol/l (range 1.1-8.1 mmol/l). There was no difference to control subjects in the exercise-induced increase in plasma levels of ammonia and hypoxanthine or in the increase in urinary hypoxanthine excretion. The findings support the hypothesis of a reduced substrate supply to the citric acid cycle in myoadenylate deaminase deficiency. The normal formation of ammonia and hypoxanthine excludes a marked loss of adenine nucleotides in working muscles in these patients.
Asunto(s)
AMP Desaminasa/deficiencia , Prueba de Esfuerzo , Enfermedades Musculares/sangre , AMP Desaminasa/genética , Adulto , Amoníaco/sangre , Ciclo del Ácido Cítrico , Análisis Mutacional de ADN , Humanos , Hipoxantina , Hipoxantinas/sangre , Hipoxantinas/orina , Lactatos/sangre , Ácido Láctico , Masculino , Persona de Mediana Edad , Enfermedades Musculares/enzimología , Enfermedades Musculares/genética , Mutación Puntual , Purinas/metabolismoRESUMEN
Nitrogen metabolism was investigated in regenerating liver-bearing rats through the following parameters: (1) liver aminoacid content, (2) plasma and urinary urea and creatinine, (3) plasma and urinary oxypurines, uric acid and allantoin. Two groups of aminoacids were considered: (1) the essential aminoacids (phenylalanine, tyrosine, isoleucine, lysine, leucine, valine, arginine, histidine and methionine); (2) the non-essential aminoacids (aspartic acid, asparagine, glutamic acid, glutamine, alanine, glycine, serine, threonine and proline). Some of the first group tended to decrease, and those of the second group to increase, immediately after partial hepatectomy. Few ketogenic aminoacids are probably oxidized to provide energy. The flux of aminoacids for gluconeogenesis is minutely controlled, therefore, those of the second group being spared at first and set aside for protein synthesis, which increases on the second and third days after partial hepatectomy. Plasma and urinary urea, oxypurines, uric acid and allantoin did not show any significant variations after partial hepatectomy. The conclusion emerging from the present research is that, although variations in aminoacid composition and metabolism and in purine nucleotide metabolism have been demonstrated to occur in the regenerating liver, the overall nitrogen catabolism, as reflected by the principal end products, does not undergo substantial variations. The remaining liver is able to fulfil this function.
Asunto(s)
Regeneración Hepática , Hígado/metabolismo , Nitrógeno/metabolismo , Alantoína/sangre , Alantoína/orina , Aminoácidos/metabolismo , Animales , Creatina/sangre , Creatina/orina , Hepatectomía , Hipoxantina , Hipoxantinas/orina , Tamaño de los Órganos , Ratas , Ratas Wistar , Urea/sangre , Urea/orina , Ácido Úrico/sangre , Ácido Úrico/orina , Xantina , Xantinas/orinaRESUMEN
Serum uric acid and oxypurines (hypoxanthine and xanthine) renal excretion of uric acid and oxypurines as well as plasma adenosine deaminase activity and AMP deaminase activity were studied in 18 patients with essential hypertension and in 17 healthy subjects. The aim of the study was to evaluate uric acid production rate in essential hypertension. Serum uric acid was significantly higher (7.04 +/- 2.03 mg% = 370.5 +/- 106 mumol/l; p < 0.01) in essential hypertension in comparison with control group (5.2 +/- 1.0 mg% = 275.0 +/- 51.9 mumol/l) and plasma oxypurines were increased insignificantly. Impairment of fractional excretion of uric acid (p < 0.05) was found in patients with essential hypertension. Plasma adenosine deaminase activity and plasma AMP deaminase activity did not differ in the studied groups. Increased production of uric acid does not contribute the incidence of hyperuricemia in essential hypertension. The results suggest that tubular defect of oxypurines excretion similar to that of uric acid exists in patients with essential hypertension.
Asunto(s)
AMP Desaminasa/sangre , Adenosina Desaminasa/sangre , Hipertensión/metabolismo , Hipoxantinas/orina , Riñón/metabolismo , Ácido Úrico/sangre , Xantinas/orina , Adulto , Femenino , Humanos , Hipertensión/sangre , Hipertensión/orina , Hipoxantina , Masculino , Persona de Mediana Edad , Valores de Referencia , XantinaRESUMEN
A reversed-phase high-performance liquid-chromatography method for determining simultaneous quantitation of purine-pyrimidine metabolites, allopurinol and oxipurinol in plasma and urine samples was studied. Separation was optimal with phosphate buffer (10 mmol/l, pH 5.0) containing 1% methanol as an eluent and mu Bondapak C18 as a column. An isocratic separation of a standard mixture of 13 compounds was achieved within 40 minutes with adequate reproducibilities (coefficient of variation: 2.49% for 1.63 mumol/l orotidin-0.12% for 50 mumol/l uridine). A simple ultrafiltration of plasma yielded quantitative recoveries (uric acid: 101.7-107.5%, hypoxanthine: 90.4-102.8%, xanthine: 95.9-99.5%, oxipurinol: 104.4-107.1%, allopurinol: 97.4-103.4%). Compounds were identified by their retention times, absorbance ratios, co-elution with standards and enzymic shifts. In addition to the above compounds, simultaneous quantitation of pseudouridine, uridine, adenine and inosine in the plasma would be possible under the same conditions.
Asunto(s)
Alopurinol/análisis , Oxipurinol/análisis , Purinas/metabolismo , Pirimidinas/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Humanos , Hipoxantina , Hipoxantinas/sangre , Hipoxantinas/orina , Ácido Úrico/sangre , Ácido Úrico/orina , Xantina , Xantinas/sangre , Xantinas/orinaRESUMEN
The pharmacokinetics of 2',3'-dideoxyinosine (ddI) were examined in rats given intravenous doses of 8, 40, or 200 mg/kg. The concentrations of ddI in whole blood and plasma were identical. The concentration decline was multiexponential, with mean half-lives of 2 and 20 min for the first and second phases, respectively. At the highest dose, a slower third phase with a half-life of 56 min was observed. The total-body clearances were 99, 77, and 37 ml/min-kg for the 8, 40, and 200 mg/kg doses. The steady-state volume of distribution showed a trend for a decrease with increasing doses, but the difference was not statistically significant. Twenty-four-hour urinary recovery of unchanged drug for the three doses was similar at about 20%, suggesting that a major fraction of the dose was metabolized. Urinary excretion of ddI metabolite, hypoxanthine, accounted for less than 5% of the dose. Renal and metabolic clearances decreased with increased doses. ddI was metabolized in blood; the addition of inorganic phosphate, a cosubstrate in phosphorylase-mediated nucleoside catabolism, enhanced the degradation by about fourfold. In summary, these data indicate equal distribution of ddI in the extracellular and intracellular spaces in blood, its enzymatic degradation in blood, and nonlinear elimination kinetics.
Asunto(s)
Didanosina/farmacocinética , Animales , Cromatografía Líquida de Alta Presión , Didanosina/administración & dosificación , Didanosina/sangre , Relación Dosis-Respuesta a Droga , Femenino , Semivida , Hipoxantina , Hipoxantinas/orina , Inyecciones Intravenosas , Ratas , Ratas Endogámicas F344RESUMEN
Urinary excretion of purine derivatives (PD) was used to estimate the microbial N (MN) supply to sheep in three experiments designed to examine the effects of DMI and BW on the efficiency of microbial N supply (EMNS) to the host animal. In Exp. 1, four sheep of about 45 kg BW were given 328, 656, 984, and 1313 g of DM/d of a hay/concentrate diet in a Latin square design. Excretion of PD per kilogram of digestible organic matter intake (DOMI) increased with intake, and EMNS increased from 12.0 to 28.3 g of MN/kg of OM digested in the rumen (DOMR). In Exp. 2, 19 sheep ranging from 22 to 73 kg BW were all offered 820 g of DM/d of the same diet as that fed in Exp. 1. Although DM digestibility was relatively constant, PD excretion varied from 4.5 to 13.5 mmol/d and EMNS from 8 to 36 g of MN/kg of DOMR, both inversely related to animal BW. In Exp. 3, five sheep of 48 to 57 kg BW were given a different diet at 702, 966, or 1,237 g of DM/d. Purine derivative excretion per kilogram of DOMI increased with the DMI:BW ratio. Calculated EMNS ranged from 23 to 35 g of MN/kg of DOMR. Pooled data from all experiments showed EMNS to be related to the DMI:BW ratio. It is suggested that the DMI:BW ratio defines the ruminal digesta passage rate and hence outflow of microbial protein. The results imply that the EMNS for a given diet is not constant, but changes with intake.