Salvage of urea-nitrogen in the large bowel: functional significance in metabolic control and adaptation.
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Adaptation, Physiological↗
Biomedical subjects
A A Jackson
Publications and source records attributed to A A Jackson.
Isolation of a RT-PCR fragment from human colon and sheep rumen RNA with nucleotide sequence similarity to human and rat urea transporter isoforms.
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Animals↗
Dietary pattern, nutrient intake and growth of adolescent school girls in urban Bangladesh.
OBJECTIVE: To investigate the dietary pattern and nutritional status of adolescent girls attending schools in Dhaka city and to examine the association with various social factors. DESIGN: Cross-sectional study. SETTING: Girls high schools in Dhaka city. SUBJECTS: A total of 384 girls, aged from 10 to 16 years, who were students of classes VI to IX of 12 girls high schools in Dhaka city were selected by systematic random sampling. Nutrient intake was assessed using the 24-h recall method and the usual pattern of food intake was examined using a 7-day food frequency questionnaire. RESULTS: The prevalence of undernutrition among the participants assessed as stunting was 10% overall with younger girls being less stunted (2%) than older girls (16%), whereas 16% were thin with relatively more of the younger girls (21%) being thin than of the older girls (12%). Based on the usual pattern of food intake, a substantial proportion of the girls did not consume eggs (26%), milk (35%) or dark green leafy vegetables (20%). By comparison, larger proportions consumed meat (50%) and fish (65%) at least four times a week. For the intake of energy and protein, only 9 and 17% of the girls, respectively, met the recommended daily allowance (RDA). For nearly 77% of the girls, the intake of fat was less than the recommendation. Intakes less than the RDA were found for iron (77% of the girls), calcium (79%), vitamin A (62%), vitamin C (67%), and riboflavin (96%). Based on the food consumption data, cereals were the major source of energy (57%), thiamin (67%), niacin (63%) and iron (37%). Animal sources supplied 50% of dietary protein. Cooking fats were the principal source of fat (67%) in the diet. Milk was the major contributor for riboflavin and preformed vitamin A (retinol). Leafy vegetables and fruits were the main sources of provitamin A (carotenes). The girls from families with less educated parents were more likely to be thin and short for their age. Those girls from families with lower incomes and less educated parents had a dietary pattern which tended to be poor with regard to egg, milk, meat and fruit, with lower intakes of protein, fat and riboflavin. CONCLUSION: The findings indicate that the diets of these girls tended to be inadequate both for macronutrients and micronutrients, with significant health implications. There was also a relationship between the family income and the education of the parents with the nutritional status of the girls.
Adolescent↗
The effect of prenatal diet and glucocorticoids on growth and systolic blood pressure in the rat.
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Animals↗
Dietary supplementation with L-methionine impairs the utilization of urea-nitrogen and increases 5-L-oxoprolinuria in normal women consuming a low protein diet.
Urea kinetics were measured in normal women after 5 d consuming a low protein diet [LP, 67 mg N/(kg.d), 0.42 g protein/(kg.d)]. To determine whether the availability of methionine limits the utilization of nonessential nitrogen from low protein diets, the study was repeated on four further occasions with the addition of dietary supplements of L-methionine, 9 mg N/(kg.d) (LP-M); urea, 52 mg N/(kg.d) (LP-U); urea and methionine (LP-UM); or urea, 26 mg N/(kg.d), and glycine, 26 mg N/(kg.d), (LP-UG). Urea kinetics were derived after prime and intermittent oral doses of [15N15N]urea from the measurements of enrichment by isotope ratio mass spectrometry in urea isolated from urine. Nitrogen balance was significantly improved when the women consumed LP-U and LP-UG, but not LP-M or LP-UM. The urinary excretion of 5-L-oxoproline was measured as a marker of glycine availability and was significantly lower when women consumed LP-U and LP-UG compared with either LP or LP-M and LP-UM. There was a significant correlation between urinary 5-L-oxoproline and urinary sulfate excretion (r = 0.68, P = 0.00003). The availability of methionine was not limiting for nitrogen metabolism when women consumed these diets, whereas the response to supplementation with urea alone or urea with glycine showed that the availability of nonessential nitrogen was limiting. Glycine is consumed in the detoxification of excess methionine, and supplementation with methionine appeared to place a competitive demand on the availability of glycine for other metabolic processes.
Adult↗
Transbilayer movement of fully ionized taurine-conjugated bile salts depends upon bile salt concentration, hydrophobicity, and membrane cholesterol content.
Taurine-conjugated bile salts mediate rapid transmembrane flux of divalent cations, irrespective of whether bile salts and divalent cations are initially on the same or opposite side of the membrane. We therefore hypothesized that ionized bile salts can equilibrate between membrane hemileaflets. We quantitated bile salt binding to large unilamellar egg yolk phosphatidylcholine (EYPC) +/- cholesterol (Ch) vesicles under conditions in which one or both hemileaflets were initially exposed to bile salts. At unbound taurodeoxycholate (TDC) concentrations >0.2 mM, the dependence of binding on TDC concentration after 30 min was indistinguishable for vesicles prepared by either method and did not change from 30 minutes to 24 h. At unbound TDC concentrations <0.1 mM, the ratio of bound/free TDC to EYPC vesicles doubled over a single exponential time course. Equilibration times were greater for the more hydrophilic bile salts taurocholate and tauroursodeoxycholate, for EYPC/Ch vesicles, and at lower temperatures. For glycine-conjugated bile salts, time-dependent changes in binding did not occur, consistent with more rapid equilibration of the small fraction of the protonated form. We conclude that fully ionized conjugated bile salts translocate between lipid bilayer hemileaflets, in contrast to previous observations that equilibration of fully ionized unconjugated bile salts occurs at a negligible rate in small unilamellar vesicles. The rate of "flip-flop" increases with increases in intramembrane bile salt concentration and hydrophobicity but decreases with cholesterol content and lower temperature. We speculate that physiologically, even in the absence of a specific membrane transporter, bile salts can gain access to intracellular compartments and mediate increases in divalent cation flux that may underlie cytotoxicity.
Bile Acids and Salts↗
Stable-isotope method for determining the gastrointestinal handling of [1-13C]palmitic acid.
The 13C enrichment in individual fatty acids extracted from human feces following the oral administration of [1-13C]palmitic acid has been determined using a novel approach based upon gas chromatography-isotope ratio mass spectrometry. The method was established and tested for precision and repeatability. Analytical precision was determined from 10 repeated injections of a sample containing 16:0 and 18:0 with levels of delta 13C abundance measured at -34.01 +/- 0.60 and -23.62 +/- 0.95 delta per mil (parts per thousand) (/1000), respectively (mean +/- SD). For the repeatability study, measurement of enrichment of the same mixture of unlabeled fatty acid methyl ester (FAME) standards (13:0, 14:0, 16:0, and 18:0) was found to have standard deviations (0.45, 0.56, 1.46 and 1.54/1000, respectively). When labeled [1-13C]palmitic acid was serially diluted with naturally enriched palmitic acid, a linear relationship was obtained to a dilution of 10% enriched compound (530/1000). FAME were prepared from two fecal samples from a normal healthy adult; the first, a baseline specimen, containing no added label and the second, followed a single oral dose of [1-13C]palmitic acid and was enriched. Enrichment in 13C was confined to the solvent-soluble fraction following lipid extraction, and was only identified with prior acidification. The enrichments were measured in triplicate, baseline sample -32.66 +/- 0.5/1000, enriched sample +268.61 +/- 8.0/1000. Enrichment was restricted to the labeled species consumed, 16:0. The methodology described here allows for the separation of compounds prior to the determination of enrichment and can be utilized to contribute to a more complete description of the gastrointestinal handling of labeled substrates than previously obtained.
Carbon Isotopes↗
Urea kinetics varies in Jamaican women and men in relation to adiposity, lean body mass and protein intake.
OBJECTIVE: We have measured urea kinetics in normal adult men and women of different body composition to determine whether adiposity is associated with differences in the rate of urea production or endogenous urea hydrolysis. DESIGN: Urea kinetics were determined from the excretion of [15N15N]urea in urine over a period of 48 h following a single oral dose of [15N15N]urea, in nine lean and nine obese women and in seven light and seven heavy males while they were consuming their habitual diets. Urinary 5-L-oxoproline was measured as an index of glycine metabolic status. SETTING: The studies were carried out in the research ward of the Tropical Metabolism Research Unit, University of the West Indies. RESULTS: Successful studies were completed in eight obese and five lean women and in six heavy and five light men. When compared with lean women, in obese women the rate of urea production and hydrolysis was significantly greater and this difference could not be accounted for by the greater fat-free mass alone, and was in part associated directly with the increase in fat mass. The rate of urea production and hydrolysis was greater in heavy men than in light men, a difference which was attributed to an increase in dietary protein. In obese women and heavy men there was a significantly higher rate of excretion of 5-L-oxoproline in urine when compared with lean women and lean men respectively. CONCLUSION: This paper highlights the difficulty in identifying an appropriate reference with which to express results in people of different body composition. In obese women urea production and the hydrolysis of urea are increased, in part related to the increased fat-free mass, but also related to the increased fat mass itself. In obese women and men on high protein diets the greater rate of hydrolysis urea may be a reflection of an increased demand for the synthesis of non-essential amino acids, especially glycine.
Adult↗
Urinary 5-L-oxoproline (pyroglutamic acid) excretion is greater in infants in Jamaica than in infants in England.
OBJECTIVE: To determine the pattern of excretion in urine of 5-L-oxoproline, as a measure of glycine status, during the first six weeks of life in Jamaican infants. DESIGN: Spot samples of urine were collected from term and preterm infants at birth and longitudinally to four weeks of age, or at six weeks of age. 5-L-oxoproline was isolated by column chromatography and hydrolysed to L-glutamic acid, which was measured enzymatically and the results expressed relative to creatinine excretion. SETTING: Maternity wards and postnatal clinic of the University Hospital of the West Indies. SUBJECTS: African-Caribbean infants, 19 term and 21 preterm, from birth to four weeks of age, and 79 term infants at six weeks of age. RESULTS: There were no differences between term and preterm infants. Excretion of 5-L-oxoproline increased progressively from birth, 141 mumol/mmol creatinine, to 270 mumol/mmol creatinine at four weeks of age. At six weeks of age, excretion was significantly greater than at birth or four weeks of age, 525 mumol/mmol creatinine. Compared with infants born in England, the excretion of 5-L-oxoproline was not different at birth, but was significantly greater in Jamaican infants at six weeks of age. CONCLUSIONS: Glycine status, indicated by increased excretion of 5-L-oxoproline, is marginal in Jamaican infants at six weeks of age, and this possibly reflects a limitation in the endogenous biosynthesis of glycine due to a dietary limitation of folate or vitamin B-12.
Chromatography↗
Enrichment in urinary ammonia and urea with hourly oral doses of [15N]glycine: evidence for a step function and a circadian rhythm in protein turnover.
1. The present study sought to determine the possible existence of a pool of proteins which turn over with life-time kinetics. The pattern of enrichment of ammonia and urea in hourly samples of urine was determined in normal adults to whom oral doses of [15N]glycine were given hourly for 36 h. The subjects received hourly meals throughout, and in six the study commenced at 06.00 hours, in five at 12.00 hours and in two at 18.00 h. 2. A plateau level of enrichment was achieved in urinary ammonia within 4-6 h. Regardless of the time at which the study started this plateau was held until about midnight, at which time there was an increase in enrichment, with a second higher plateau 5-6 h later. The second plateau was held to the end of the study. For urinary urea the rate of rise in enrichment was slower and smoother, because of the slow turnover of the urea pool. 3. Protein synthesis, derived from the first ammonia plateau, 179 mg h-1 kg-1, was significantly higher than that derived from the second plateau, 118 mg h-1 kg-1. Using the plateau in urea towards the end of the 36 h, the estimate of protein synthesis was 153 mg h-1 kg-1. 4. The results are considered to provide evidence of a pool of proteins for which degradation takes place in harmony with a circadian rhythm.
Adult↗
Urea kinetics in healthy women during normal pregnancy.
Urea kinetics were measured in normal women aged 22-34 years at weeks 16, 24 and 32 on either their habitual protein intake (HABIT) or a controlled intake of 60 g protein/d (CONTROL), using primed-intermittent oral doses of [15N15N]urea and measurement of plateau enrichment in urinary urea over 18 h (ID) or a single oral dose of [15N15N]urea and measurement of enrichment of urea in urine over the following 48 h (SD). The intake of protein during HABIT-ID (80 g/d) was greater than that on HABIT-SD (71 g/d); urea production as a percentage of intake was significantly greater at week 16 for HABIT-ID than HABIT-SD, whereas urea hydrolysis at week 16 was greater for HABIT-SD than HABIT-ID and urea excretion at week 32 was greater for HABIT-ID than HABIT-SD. The combined results for HABIT-ID and HABIT-SD showed a significant reduction in urea production at week 32 compared with week 24. Urea excretion decreased significantly from week 16 to week 24 with no further decrease to week 32 and urea hydrolysis was significantly greater at week 24 than either week 16 or week 32. Compared with HABIT, on CONTROL there was a decrease in urea production at week 16, and urea excretion was significantly reduced at week 16. For all time periods urea production was closely related to the sum of intake plus hydrolysis. Hydrolysis was greatest at week 24 and closely related to urea production. There was a significant inverse linear relationship overall for hydrolysis as a proportion of production and excretion as a proportion of intake. The results show that on HABIT N is more effectively conserved in mid-pregnancy through an increase in urea hydrolysis and salvage, and during late pregnancy through a reduction in urea formation. Lowering protein intake at any stage of pregnancy increased the hydrolysis and salvage of urea. The staging of these changes was later than that in pregnancy in Jamaica.
Adult↗
Comparison of urinary 5-L-oxoproline (L-pyroglutamate) during normal pregnancy in women in England and Jamaica.
Urinary 5-L-oxoproline was measured during normal pregnancies in Southampton, England and Kingston, Jamaica. The CV of 5-L-oxoproline excretion in urine, determined over 7 d in a non-pregnant woman and three pregnant women, was 10-36%. Compared with non-pregnant women, urinary 5-L-oxoproline increased three to four times from early pregnancy in women in Southampton, a highly significant difference, and remained elevated at similar levels during mid and late pregnancy. For women in Kingston, the excretion of 5-L-oxoproline was similar to that of Southampton women in the non-pregnant group and during early pregnancy. However, there was a progressive increase in the excretion of 5-L-oxoproline as pregnancy advanced and by late pregnancy excretion was from three to ten times greater than the average for the non-pregnant women. There was a significant difference between the women in Southampton and the women in Kingston during mid and late pregnancy, with women in Kingston excreting twice as much 5-L-oxoproline during late pregnancy. If the excretion of 5-L-oxoproline is a measure of glycine insufficiency, the results would indicate that in some pregnancies the ability of the mother to provide glycine for herself and the developing fetus is marginal or inadequate and the constraint appears more marked in Jamaica than in England.
Adult↗
Fetal exposure to low protein maternal diet alters the susceptibility of young adult rats to sulfur dioxide-induced lung injury.
The maternal diet is an important determinant of glutathione-related metabolism in rats. Glutathione (GSH) may play a major role in the detoxification of sulfur dioxide (SO2) within the lungs. The effects of fetal exposure to a low protein maternal diet upon later susceptibility to pulmonary injury induced by chronic SO2 exposure were evaluated in young adult rats. Pregnant rats were fed purified diets containing 180 g casein/kg (control diet) or 120, 90 or 60 g casein/kg (experimental diets). After parturition, all dams were fed a standard non-purified diet (189 g protein/kg diet). The pups thus differed only in terms of protein nutrition during gestation. At seven wk of age the male pups were housed in either room air or 286 microg SO2/m3 for 5 h/d during a 28-d period. At the end of the final SO2 treatment period, the rats exposed to 90 or 60 g casein/kg diets in utero exhibited significantly greater pulmonary injury, as assessed by bronchoalveolar lavage, than did those exposed to control diet in utero. Significant maternal diet-induced differences in activities of enzymes of the gamma-glutamyl cycle were noted in the lungs and livers of rats which had not undergone SO2 treatment. Furthermore, the response of these enzyme activities to SO2 treatment was determined by prior exposure to the maternal diet. SO2-treated rats exposed to control diet (180 g casein/kg) and low protein diet (60 g casein/kg), but not those exposed to 120 or 90 g casein/kg diets, tended to augment the activities, relative to rats not treated with SO2, of enzymes which maintain tissue GSH status either through synthesis or recycling. Differences in susceptibility to SO2-induced tissue injury may be related to programming of GSH metabolism by the maternal diet. Alternatively, impaired immune and acute phase responses to an inflammatory insult may account for a failure to resolve initial SO2-induced injury in rats exposed to low protein maternal diets.
Air Pollutants↗
Urinary excretion of 5-L-oxoproline (pyroglutamic acid) during early life in term and preterm infants.
Urinary 5-L-oxoproline was measured in term and preterm infants from shortly after birth until 6 weeks of postnatal age to determine their ability to synthesise glycine. In term infants the excretion was five to 10 times that seen in normal adults, increasing from 105 mumol/mmol creatinine in the first 72 hours after birth to 170 mumol/mmol creatinine at 6 weeks of age. There was a significant inverse linear correlation between the excretion of 5-L-oxoproline and length of gestation or birthweight. By 6 weeks of age there was no longer a significant difference in 5-L-oxoproline between term and preterm infants. There was no difference in the excretion of 5-L-oxoproline between boys and girls, or between infants fed on human milk or an artificial formula. If, in part, variability in the excretion of 5-L-oxoproline is determined by the extent to which the endogenous formation of glycine is adequate, then glycine formation may be marginal during early life, more so in preterm than in term infants, providing additional evidence that glycine is a conditionally essential amino acid in the neonate.
Birth Weight↗
Maintenance of maternal diet-induced hypertension in the rat is dependent on glucocorticoids.
Recent epidemiological evidence suggests that adult cardiovascular risk is determined by birth weight and factors that influence birth weight, such as maternal nutrition. Data from animal models suggest that an interaction between nutrition and glucocorticoid hormones "programs" increased risk of adult hypertension. Increased fetal exposure to maternal glucocorticoids that is proposed to occur from a reduction in the placental barrier to maternal glucocorticoid, 11beta-hydroxysteroid dehydrogenase, is suggested to program hypertension in the resultant offspring from both glucocorticoid-treated and maternally protein-restricted rats. The extent to which postnatal glucocorticoid stimulation may influence the progression of hypertension in the offspring from protein-restricted rat dams was assessed in 6-week-old male Wistar rats, prenatally exposed to either an 18% casein (control) or 9% casein (low protein) diet. Rats from each dietary group were sham operated, adrenalectomized or adrenalectomized, and treated with 20 mg corticosterone/kg body weight per day. Before surgery, systolic blood pressure was significantly higher in the low protein-exposed rats compared with controls (165+/-3.8 versus 142+/-3.3 mm Hg, P<.0001). Adrenalectomy of the low protein-exposed animals significantly reduced the blood pressure to control levels, while corticosterone replacement restored the hypertensive state. No effect of adrenalectomy on blood pressure was observed in 18% casein controls. In both dietary groups adrenalectomy decreased brain, but not hepatic, glucocorticoid-sensitive enzyme activities and corticosterone treatment elevated activities of all enzymes. The data suggest that maternal diet-induced hypertension is dependent on an intact adrenal gland postnatally and that glucocorticoids are key trophic agents in maintaining the high blood pressure.
11-beta-Hydroxysteroid Dehydrogenases↗
Effects of submicellar bile salt concentrations on biological membrane permeability to low molecular weight non-ionic solutes.
Bile salts have been hypothesized to mediate cytotoxicity by increasing membrane permeability to aqueous solutes. We examined whether submicellar bile salt concentrations affect model and native membrane permeability to small uncharged molecules such as water, urea, and ammonia. Osmotic water permeability (Pf) and urea permeability were measured in large unilamellar vesicles composed with egg yolk phosphatidylcholine (EYPC) +/- cholesterol (Ch) or rat liver microsomal membranes by monitoring self-quenching of entrapped carboxyfluorescein (CF). Ammonia permeability was determined utilizing the pH dependence of CF fluorescence. Submicellar bile salt concentrations did not significantly alter Pf of EYPC +/- Ch or rat liver microsomal membranes. At taurodeoxycholate (TDC) or tauroursodeoxycholate concentrations approaching those that solubilized membrane lipids, CF leakage occurred from vesicles, but Pf remained unchanged. Higher bile salt concentrations (0.5-2 mM TDC) did not alter Pf of equimolar EYPC/Ch membranes. The activation energy for transmembrane water flux was unchanged (12.1 +/- 1.2 kcal/mol for EYPC) despite the presence of bile salts in one or both membrane hemileaflets, suggesting strongly that bile salts do not form transmembrane pores that facilitate water flux. Furthermore, submicellar bile salt concentrations did not increase membrane permeability to urea or ammonia. We conclude that at submicellar concentrations, bile salts do not form nonselective convective channels that facilitate transmembrane transport of small uncharged molecules. These results suggest that bile salt-mediated transport of specific substrates, rather than nonselective enhancement of membrane permeability, underlies bile salt cytotoxicity for enterocytes and hepatocytes.
Ammonia↗
Nutritional influences in early life upon obesity and body proportions.
Close relationships exist between patterns of intra-uterine growth and the risk of ischaemic heart disease, hypertension, diabetes, insulin-resistance syndrome, obesity and some cancers later in life. Earlier studies placed emphasis on low birth weight and reduced growth, but it is now clear that disproportions in early growth are of great importance. Disproportion may be identified as disproportions of fetal and placental growth (and the risk of high blood pressure), or in head circumference, length and weight. It is hypothesized that the availability of nutrients at different times during gestation, by interacting with the maternal and fetal hormonal profile, predisposes to different patterns of growth. The same interaction programmes critical metabolic functions and determines the metabolic capacity at all later ages. People who were exposed to severe undernutrition during the Dutch hunger winter showed increased adiposity if the exposure was during early pregnancy, but decreased adiposity if the exposure was during late pregnancy. In men born in the UK, those with evidence of retarded fetal growth had significantly greater waist/hip circumference ratios for any given body mass index (the ratio fell with increasing weight at one year of age). In Mexican-Americans and non-Hispanic Caucasian Americans, people in the lowest third of birth weight had more truncal fat than those in the highest third. Offspring of rats exposed to marginally reduced protein intakes during pregnancy manifest a similar pattern of growth and metabolic change to that seen in humans, with perturbations of appetite and body fat patterning. Studies in rats suggest that programming of the hypothalamus, especially the hypothalamic-pituitary-adrenal axis might be the mechanism through which these changes are brought about.
Aging↗
Sulphur dioxide: a potent glutathione depleting agent.
Sulphur dioxide (SO2) is an air pollutant implicated in the initiation of asthmatic symptoms. Glutathione (GSH) has been proposed to play a role in detoxification of SO2 through the sulfitolysis of glutathione disulphide (GSSG) to S-sulphoglutathione (GSSO3-). Rats were exposed to concentrations of SO2 between 5 and 100 ppm for 5 hr a day between 7 and 28 days. Lung injury as assessed by bronchoalveolar lavage and tissue GSH status were evaluated. SO2 5 ppm failed to elicit any lung injury or inflammatory response but did deplete GSH pools in lung, liver, heart and kidney. Activities of gamma-glutamylcysteine synthetase (GCS), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GRed) in lung were lowered relative to those in control animals. In liver, GRed activity was decreased. SO2 50 ppm exposure also failed to elicit injury or inflammation but did lower inflammatory cell numbers in the circulation. Rats exposed to 50 ppm SO2 maintained tissue GSH status, but activities of GCS, GPx, GRed and gamma-glutamyltranspeptidase in lung and hepatic GRed and GPx were significantly lower than in control rats. Unaltered GST activity in lung and liver was suggestive of an impairment of the sulfitolysis reaction in these animals, perhaps through lower substrate flux through the GPx reaction, as GSSO3- is a known inhibitor of GST in the rat. Rats exposed to 100 ppm SO2 exhibited evidence of inflammation (120-fold increase in neutrophil numbers recovered in lavage fluid) and like the 5 ppm exposed rats had lower tissue GSH concentrations and GSH-related enzyme activities in lung. We conclude that sulfitolysis of GSSG does occur in vivo during SO2 exposure and that SO2, even in the absence of pulmonary injury, is a potent glutathione depleting agent.
Air Pollutants↗