Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-27T00:56:46.523Z Has data issue: false hasContentIssue false
  • English
  • Français

The transfer of 15N from urea to lysine in the human infant

Published online by Cambridge University Press:  09 March 2007

D. Joe Millward ,
Terrance Forrester ,
Eric Ah-Sing ,
Nana Yeboah ,
Neil Gibson ,
Asha Badaloo ,
M. Boyne ,
M. Reade ,
C. Persaud  and
Alan Jackson
D. Joe Millward*
Affiliation:
Centre for Nutrition and Food Safety, School of Biological Sciences, University of Surrey, Guildford GU2 5XH, UK
Terrance Forrester
Affiliation:
Tropical Metabolism Research Unit, University of the West Indies, Jamaica
Eric Ah-Sing
Affiliation:
Centre for Nutrition and Food Safety, School of Biological Sciences, University of Surrey, Guildford GU2 5XH, UK
Nana Yeboah
Affiliation:
Centre for Nutrition and Food Safety, School of Biological Sciences, University of Surrey, Guildford GU2 5XH, UK
Neil Gibson
Affiliation:
Centre for Nutrition and Food Safety, School of Biological Sciences, University of Surrey, Guildford GU2 5XH, UK
Asha Badaloo
Affiliation:
Tropical Metabolism Research Unit, University of the West Indies, Jamaica
M. Boyne
Affiliation:
Tropical Metabolism Research Unit, University of the West Indies, Jamaica
M. Reade
Affiliation:
Tropical Metabolism Research Unit, University of the West Indies, Jamaica
C. Persaud
Affiliation:
Institute of Human Nutrition, University of Southampton, Southampton SO16 6YD, UK
Alan Jackson
Affiliation:
Institute of Human Nutrition, University of Southampton, Southampton SO16 6YD, UK
*
*Corresponding author: Professor Joe Millward, fax + 44 (0) 1483 259 297, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

To explore the nutritional significance of urea hydrolysis for human subjects, male infants being treated for severe undernutrition were given oral doses of 10 mg [15N15N]urea every 3 h for 36 h, on admission, during rapid growth and after repletion with either moderate or generous intakes of protein. Urea hydrolysis was calculated from the 15N enrichment of urinary urea, and where possible, lysine, alanine, glycine and histidine were isolated from urine by preparative ion-exchange chromatography for measurement of 15N enrichment. Sufficient N was obtained for 15N enrichment of lysine to be measured on fifteen occasions from six children. Urea hydrolysis accounted for half of all urea production with 130 (sd 85) mg N/kg hydrolysed per d, most of which appeared to be utilized in synthetic pathways. Of the samples analysed successfully, nine samples of lysine were enriched with 15N (mean atom percent excess 0·0102, range 0·0017–0·0208) with relative enrichment ratios with respect to lysine of 1·63 (range 0·18–3·15), 1·96 (range 0·7–3·73) and 0·9 (range 0·4–1·8) for glycine, alanine and histidine respectively. Enriched samples were identified at each treatment phase and 68 % of the variation in lysine enrichment was explained by the variation in urea enrichment with 54 % explained by the overall rate of delivery of 15N to the lower gastrointestinal tract. The results indicate a minimum of 4·7 mg lysine per kg body weight made available by de novo synthesis with the more likely value an order of magnitude higher. Thus, urea hydrolysis can improve the quality of the dietary protein supply by enabling an increased supply of lysine and other indispensable amino acids.To explore the nutritional significance of urea hydrolysis for human subjects, male infants being treated for severe undernutrition were given oral doses of 10 mg [15N15N]urea every 3 h for 36 h, on admission, during rapid growth and after repletion with either moderate or generous intakes of protein. Urea hydrolysis was calculated from the 15N enrichment of urinary urea, and where possible, lysine, alanine, glycine and histidine were isolated from urine by preparative ion-exchange chromatography for measurement of 15N enrichment. Sufficient N was obtained for 15N enrichment of lysine to be measured on fifteen occasions from six children. Urea hydrolysis accounted for half of all urea production with 130 (sd 85) mg N/kg hydrolysed per d, most of which appeared to be utilized in synthetic pathways. Of the samples analysed successfully, nine samples of lysine were enriched with 15N (mean atom percent excess 0·0102, range 0·0017–0·0208) with relative enrichment ratios with respect to lysine of 1·63 (range 0·18–3·15), 1·96 (range 0·7–3·73) and 0·9 (range 0·4–1·8) for glycine, alanine and histidine respectively. Enriched samples were identified at each treatment phase and 68 % of the variation in lysine enrichment was explained by the variation in urea enrichment with 54 % explained by the overall rate of delivery of 15N to the lower gastrointestinal tract. The results indicate a minimum of 4·7 mg lysine per kg body weight made available by de novo synthesis with the more likely value an order of magnitude higher. Thus, urea hydrolysis can improve the quality of the dietary protein supply by enabling an increased supply of lysine and other indispensable amino acids.To explore the nutritional significance of urea hydrolysis for human subjects, male infants being treated for severe undernutrition were given oral doses of 10 mg [15N15N]urea every 3 h for 36 h, on admission, during rapid growth and after repletion with either moderate or generous intakes of protein. Urea hydrolysis was calculated from the 15N enrichment of urinary urea, and where possible, lysine, alanine, glycine and histidine were isolated from urine by preparative ion-exchange chromatography for measurement of 15N enrichment. Sufficient N was obtained for 15N enrichment of lysine to be measured on fifteen occasions from six children. Urea hydrolysis accounted for half of all urea production with 130 (sd 85) mg N/kg hydrolysed per d, most of which appeared to be utilized in synthetic pathways. Of the samples analysed successfully, nine samples of lysine were enriched with 15N (mean atom percent excess 0·0102, range 0·0017–0·0208) with relative enrichment ratios with respect to lysine of 1·63 (range 0·18–3·15), 1·96 (range 0·7–3·73) and 0·9 (range 0·4–1·8) for glycine, alanine and histidine respectively. Enriched samples were identified at each treatment phase and 68 % of the variation in lysine enrichment was explained by the variation in urea enrichment with 54 % explained by the overall rate of delivery of 15N to the lower gastrointestinal tract. The results indicate a minimum of 4·7 mg lysine per kg body weight made available by de novo synthesis with the more likely value an order of magnitude higher. Thus, urea hydrolysis can improve the quality of the dietary protein supply by enabling an increased supply of lysine and other indispensable amino acids.To explore the nutritional significance of urea hydrolysis for human subjects, male infants being treated for severe undernutrition were given oral doses of 10 mg [15N15N]urea every 3 h for 36 h, on admission, during rapid growth and after repletion with either moderate or generous intakes of protein. Urea hydrolysis was calculated from the 15N enrichment of urinary urea, and where possible, lysine, alanine, glycine and histidine were isolated from urine by preparative ion-exchange chromatography for measurement of 15N enrichment. Sufficient N was obtained for 15N enrichment of lysine to be measured on fifteen occasions from six children. Urea hydrolysis accounted for half of all urea production with 130 (sd 85) mg N/kg hydrolysed per d, most of which appeared to be utilized in synthetic pathways. Of the samples analysed successfully, nine samples of lysine were enriched with 15N (mean atom percent excess 0·0102, range 0·0017–0·0208) with relative enrichment ratios with respect to lysine of 1·63 (range 0·18–3·15), 1·96 (range 0·7–3·73) and 0·9 (range 0·4–1·8) for glycine, alanine and histidine respectively. Enriched samples were identified at each treatment phase and 68 % of the variation in lysine enrichment was explained by the variation in urea enrichment with 54 % explained by the overall rate of delivery of 15N to the lower gastrointestinal tract. The results indicate a minimum of 4·7 mg lysine per kg body weight made available by de novo synthesis with the more likely value an order of magnitude higher. Thus, urea hydrolysis can improve the quality of the dietary protein supply by enabling an increased supply of lysine and other indispensable amino acids.

Keywords

UndernutritionUreaAmino acidsStable isotopes
Type
Research Article
Information
British Journal of Nutrition , Volume 83 , Issue 5 , May 2000 , pp. 505 - 512
Copyright
Copyright © The Nutrition Society 2000

References

Badaloo, A, Boyne, M, Reade, M, Persaud, C, Forrester, T, Millward, DJ and Jackson, A (1999) Dietary protein, growth and urea kinetics in severely malnourished children and during recovery. Journal of Nutrition 129, 969–979.CrossRefGoogle ScholarPubMed
Bundy, R, Hounslow, A, Persaud, C, Murphy, J, Wooton, SA and Jackson, AA (1996) Metabolism of lactose–ureide labelled with 15N and13C in humans. Proceedings of the Nutrition Society 55, 38A.Google Scholar
Dantzig, AH, Hoskins, J, Tabas, LB, Bright, S, Shepard, RL, Jenkins, IL, Duckworth, DC, Sportsman, JR, Maekensen, D, Rosteck, PR and Skatrud, PL (1994) Association of intestinal peptide transport with a protein related to the cadherin superfamily. Science 264, 430–433.CrossRefGoogle Scholar
de Benoist, B, Abdulrazzak, Y, Brooke, OG, Halliday, D and Millward, DJ (1984) The measurement of whole body protein turnover in the preterm infant with intragastric infusion of L-[1-13C]leucine and sampling of the urinary leucine pool. Clinical Science 66, 155–164.CrossRefGoogle ScholarPubMed
Fuller, MF and Reeds, PJ (1998) Nitrogen cycling in the gut. Annual Review of Nutrition 18, 385–411.CrossRefGoogle ScholarPubMed
Furst, P (1972) 15N studies in severe renal failure. 2. Evidence for the essentiality of histidine. Scandinavian Journal of Clinical and Laboratory Investigation 30, 307–312.CrossRefGoogle Scholar
Gibson, NRAh-Sing, E, Badaloo, A, Forrester, T, Jackson, A and Millward, DJ (1997) Transfer of 15N from urea to the circulating dispensable and indispensable amino acid pool in the human infant. Proceedings of the Nutrition Society 56, 79A.Google Scholar
Giordano, C, de Pascale, C, Baliestrieri, C, Cittadini, D and Crescenzi, A (1968) Incorporation of urea 15N in amino acids of patients with chronic renal failure on low nitrogen diet. American Journal of Clinical Nutrition 21, 394–404.CrossRefGoogle ScholarPubMed
Heine, W, Mohr, C, Wuttzke, KD and Radke, M (1991) Symbiotic interactions between colonic microflora and protein metabolism in infants. Acta Pediatrica Scandinavica 80, 7–12.CrossRefGoogle ScholarPubMed
Heine, W, Tiess, M, Stolpe, HJ and Wutzke, K (1984) Urea utilisation by the intestinal flora, of infants fed mother's milk and as a formula diet, as measured with 15N. Journal of Pediatrics Gastroenterology and Nutrition 3, 709–712.Google ScholarPubMed
Heine, W, Tiess, M and Wutzke, KD (1986) 15N-tracer investigation of the physiological availability of urea nitrogen in mother's milk. Acta Pediatrica Scandinavica 75, 539–543.CrossRefGoogle ScholarPubMed
Heine, W, Wutzke, KD, Richter, I, Walther, F and Plath, C (1987) Evidence for colonic absorption of protein nitrogen in infants. Acta Pediatrica Scandinavica 76, 741–744.CrossRefGoogle ScholarPubMed
Hibbert, JM and Jackson, AA (1992) Variation in measures of urea kinetics over four years in a single adult. European Journal of Clinical Nutrition 45, 347–351.Google Scholar
Jackson, AA (1998) Salvage of urea-nitrogen in the large bowel: functional significance in metabolic control and adaptation. Biochemical Society Transactions 26, 231–237.CrossRefGoogle ScholarPubMed
Jackson, AA, Bundy, R, Hounslow, A, Persaud, C, Murphy, J and Wooton, SA (1999) Metabolism of lactose-ureide labelled with 15N and 13C in humans. Clinical Science 97, 547–555.CrossRefGoogle Scholar
Jackson, AA, Doherty, J, de Benoist, MH, Hibbert, J and Persaud, C (1990) The effect of the level of dietary protein, carbohydrate and fat on urea kinetics in young children during rapid catch-up weight gain. British Journal of Nutrition 64, 371–385.CrossRefGoogle ScholarPubMed
Jackson, AA & Golden, MHN (1987) Severe malnutrition. In Oxford Textbook of Medicine, pp. 812–828 [Weatherall, DJ, Ledingham, JGG & Warrell, DA, editors]. Oxford: Oxford Medical Publications.Google Scholar
Jackson, AA, Picou, D and Landman, J (1984) The non-invasive measurement of urea kinetics in normal man by a constant infusion of 15N15N-urea. Human Nutrition: Clinical Nutrition 38, 339–354.Google Scholar
Kaplan, A (1965) Urea nitrogen and ammonia nitrogen. In Standard Methods in Clinical Chemistry, pp. 245–256 [Meites, S, editor]. New York: Academic Press.Google Scholar
Kennedy, N, Badaloo, AV and Jackson, AA (1990) Adaptation to a marginal intake of energy in young children. British Journal of Nutrition 63, 145–154.CrossRefGoogle ScholarPubMed
Moran, BJ and Jackson, AA (1990) Metabolism of 15N-labelled urea in the functioning and defunctioned human colon. Clinical Science 79, 253–258.CrossRefGoogle ScholarPubMed
Moran, BJ and Jackson, AA (1990) 15N-urea metabolism in the functioning human colon: luminal hydrolysis and mucosal permeability. Gut 31, 454–457.CrossRefGoogle ScholarPubMed
Olszewski, A and Buraczewski, S (1978) Absorption of amino acids in isolated pig caecum in situ. Effect of concentration of enzymatic casein hydrolysate on absorption of amino acids. Acta Physiologica Polanski 29, 67–77.Google ScholarPubMed
Rikimaru, T, Fujita, Y, Okuda, T, Kajiwara, N, Date, C, Heywood, PF, Alpers, MP and Koishi, H (1984) Utilization of urea nitrogen in Papua New Guinea highlanders. Journal of Nutritional Science and Vitaminology 31, 393–402.CrossRefGoogle Scholar
Schoenheimer, R and Ratner, S (1939) Studies in protein metabolism. 3. Synthesis of amino acids containing isotopic nitrogen. Journal of Biological Chemistry 127, 301–313.CrossRefGoogle Scholar
Sheng, Y-B, Badger, TM, Asplund, JM and Wixom, RL (1977) Incorporation of 15NH4Cl into histidine in adult man. Journal of Nutrition 107, 621–630.CrossRefGoogle ScholarPubMed
Snyderman, SE (1967) Urea as a source for unessential nitrogen for the human. In Urea as a Protein Supplement, pp. 441–445 [Briggs, M, editor]. Oxford: Pergamon.CrossRefGoogle Scholar
Steinbrecher, HA, Griffith, DM and Jackson, AA (1996) Urea kinetics in normal breast-fed infants measured with primed/intermittent oral doses of [15N,15N]urea. Acta Paediatrica 85, 656–662.CrossRefGoogle Scholar
Tanaka, N (1982) Urea utilization in protein deficient rats. Journal of the Japanese Society for Nutrition and Food Science 35, 175–180.Google Scholar
Tanaka, N, Kubo, K, Shiraki, K, Koishi, H and Yoshimura, H (1980) A pilot study on protein metabolism in Papua New Guinea highlanders. Journal of Nutritional Science and Vitaminology 26, 247–259.CrossRefGoogle ScholarPubMed
Torrallardona, D, Harris, CI, Coates, ME and Puller, MF (1996) Microbial amino acid synthesis and utilization in rats: incorporation of 15N from 15NH4Cl into lysine in the tissues of germ-free and conventional rats. British Journal of Nutrition 76, 689–700.CrossRefGoogle ScholarPubMed
Torrallardona, D, Harris, CI and Fuller, MF (1996) Microbial amino acid synthesis and utilization in rats: the role of coprophagy. British Journal of Nutrition 76, 701–709.CrossRefGoogle ScholarPubMed
Torrallardona, D, Harris, CI, Milne, E & Fuller, MF (1996c) Site of absorption of lysine synthesis by the gastrointestinal microflora of pigs. In Proceedings of the VII International Symposium on Protein Metabolism and Nutrition, pp. 369–371 [Nunes, AF, Portugal, AV, Costa, JP and Ribeiro, JR, editors]. Santarim: European Association of Animal Production.Google Scholar
Torrallardona, D, Harris, CIMilne, E & Fuller, MF (1994) The contribution of intestinal microflora to amino acid requirements in pigs. In Proceedings of the 6th International Symposium on the Digestion and Physiology of Pigs, pp. 245–248 [Souffiant, WB, and Hagemeister, H, editors]. Dummerstoif Forsch Inst. Biol. Landwirtsch Nutztiere.Google Scholar
Walser, M, George, J and Bodenlos, LJ (1954) Altered proportions of isotopes of molecular nitrogen from biological samples for mass spectrometry. Journal of Chemical Physiology 22, 1146–1151.CrossRefGoogle Scholar
Waterlow, JC, Garlick, PJ & Millward, DJ (1978) Protein Turnover in Mammalian Tissues and the Whole Body. Amsterdam: Elsevier/North-Holland Biomedical Press.Google Scholar
Wrong, OM, Vince, AJ and Waterlow, JC (1985) The contribution of endogenous urea to faecal ammonia in man, determined by 15N labelling of plasma urea. Clinical Science 68, 193–199.CrossRefGoogle ScholarPubMed
Yeboah, NAh-Sing, E, Badaloo, A, Forrester, T, Jackson, A and Millward, DJ (1996) Transfer of 15N from urea to the circulating lysine pool in the human infant. Proceedings of the Nutrition Society 55, 37A.Google Scholar