Phenylalanine Kinetics in Sick Preterm Neonates with Respiratory Distress Syndrome

Shortland, Graham; Walter, J H; Fleming, Peter; Halliday, D.

doi:10.1203/00006450-199412000-00005

Cited by 22 publications

(7 citation statements)

References 25 publications

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“…Phenylalanine hydroxylase status was investigated in sick preterm neonates with respiratory distress syndrome 50. The results obtained in this study did not support the hypothesis that the enzyme activity was low in these preterm infants.…”

Section: Macronutrient Metabolismcontrasting

confidence: 83%

Uses of stable isotopes in clinical diagnosis and research in the paediatric population

Bodamer

2001

Archives of Disease in Childhood

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The landmark experiments of Schoenheimer and Rittenberg in the 1930s provided the scientific foundation for the ensuing development and application of stable isotope techniques in clinical diagnosis and research. Following intravascular or oral administration, the tracer is metabolically indistinguishable from the equivalent unlabelled compound of interest (tracee). The metabolic fate of the compound can be assessed qualitatively and quantitatively by measuring the relative abundance of tracer and tracee and/or their respective metabolites with time. The detectable mass diVerence of tracer and tracee allows the analysis of compounds, extracted from plasma, by gas chromatography-mass spectrometry (GC-MS, picogram sample size, analytical range 0.1-100 mole %, precision ±0.2 mole %). 5The detection limit is considerably less than 0.1 mole %, when tracers with multiple stable isotope labels (for example ring-D 5 phenylalanine) are used.6 Stable isotopes in breath ( 12 CO 2 and 13 CO 2 ) are analysed using an isotope ratio mass spectrometer (IRMS, microgram sample size, analytical range 0.0001-0.01 atom % excess, precision ±0.0001 atom %. Combustion IRMS has essentially the same analytical capabilities as IRMS but allows the combustion of tissue samples with subsequent analysis of gaseous isotope enrichment. 4 Stable isotopes of minerals are typically analysed by thermal ionisation mass spectrometry (TIMS) or inductively coupled plasma mass spectrometry (ICP-MS) with high precision and sensitivity.

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Section: Macronutrient Metabolismcontrasting

confidence: 83%

Uses of stable isotopes in clinical diagnosis and research in the paediatric population

Bodamer

2001

Archives of Disease in Childhood

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“…Phenylalanine hydroxylation to tyrosine measured by plasma enrichments modified from Ref. 26, reprinted with permission from Elsevier. Mean (ϮSE) phenylalanine hydroxylation at graded tyrosine intakes.…”

Section: Discussionmentioning

confidence: 99%

“…It was therefore concluded that, by use of this model at intakes of tyrosine below the mean requirement as estimated by House et al (9), and at high intakes of phenylalanine, measurements of phenylalanine hydroxylation were overestimated. Subsequent examination of results from previous studies of phenylalanine metabolism in TPN-fed neonates (2,15,26) also indicates that rates of hydroxylation appeared to be overestimated. Similarly, we showed in adult humans that rates of phenylalanine hydroxylation are overestimated (27) at low tyrosine intakes.…”

mentioning

confidence: 80%

“…This model used the ratio of the plasma enrichment of tyrosine to phenylalanine, representing the product and precursor pools of hydroxylation, respectively, and tyrosine flux to calculate the rate of phenylalanine hydroxylation (5). Although originally developed for use in the fasted state, the Clarke and Bier model, and its modified version (19), were subsequently applied to studies in the fed state in parenterally fed neonates using intravenously administered isotope infusions (2,4,7,15,26,28). The results of these studies indicated that parenterally fed neonates have the ability to hydroxylate phenylalanine.…”

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confidence: 99%

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In vivo regulation of phenylalanine hydroxylation to tyrosine, studied using enrichment in apoB-100

Rafii¹,

McKenzie²,

Roberts³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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Phenylalanine hydroxylation is necessary for the conversion of phenylalanine to tyrosine and disposal of excess phenylalanine. Studies of in vivo regulation of phenylalanine hydroxylation suffer from the lack of a method to determine intrahepatocyte enrichment of phenylalanine and tyrosine. apoB-100, a hepatic export protein, is synthesized from intrahepatocyte amino acids. We designed an in vivo multi-isotope study, [(15)N]phenylalanine and [2H2]tyrosine to determine rates of phenylalanine hydroxylation from plasma enrichments in free amino acids and apoB-100. For independent verification of apoB-100 as a reflection of enrichment in the intrahepatocyte pool, [1-(13)C]lysine was used as an indicator amino acid (IAA) to measure in vivo changes in protein synthesis in response to tyrosine supplementation. Adult men (n = 6) were fed an amino acid-based diet with low phenylalanine (9 mg.kg(-1).day(-1), 4.54 mumol.kg(-1).,h(-1)) and seven graded intakes of tyrosine from 2.5 (deficient) to 12.5 (excess) mg.kg(-1).day(-1). Gas chromatography-quadrupole mass spectrometry did not detect any tracer in apoB-100 tyrosine. A new and more sensitive method to measure label enrichment in proteins using isotope ratio mass spectrometry demonstrated that phenylalanine hydroxylation measured in apoB-100 decreased linearly in response to increasing tyrosine intake and reached a break point at 6.8 mg.kg(-1).day(-1). IAA oxidation decreased with increased tyrosine intake and reached a break point at 6.0 mg.kg(-1).day(-1). We conclude: apoB-100 is an accurate and useful measure of changes in phenylalanine hydroxylation; the synthesis of tyrosine via phenylalanine hydroxylation is regulated to meet the needs for protein synthesis; and that plasma phenylalanine does not reflect changes in protein synthesis.

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“…A similar close agreement between measured and predicted estimates of tyrosine flux has been reported in a study of preterm neonates suffering from respiratory distress syndrome. 38 It is a necessary condition for the measurement of whole body protein turnover by means of primed constant infusion that steady state conditions prevail with respect to isotopic enrichment and the concentrations of the tracers. We show this to be the case in our study population (fig 2, table 2).…”

Section: Determination Of 3c02 Recoverymentioning

confidence: 99%

Whole body protein metabolism in children with cancer.

Daley

Pearson²,

Craft³

et al. 1996

Archives of Disease in Childhood

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Cachexia is a complex and extremely variable syndrome characterised by weight loss, anorexia, and negative nitrogen balance and is present in many cancer patients during the course of their disease.' 2 In children the cachexia is usually a result of the treatment rather than of the cancer itself. Moreover the protein requirements of children during therapy for malignancy are unknown, both at diagnosis when there is a large tumour burden and during treatment when there are the effects of anticancer drugs and infection. The aetiology of cachexia in children with cancer is multifactorial. Inadequate intake arising from anorexia, mucositis, or malabsorption due to the effects of anticancer drugs, and systemic metabolic factors arising from the effects of the malignancy, chemotherapy, or infection are likely to be contributory. However, since malignancies are typically very chemosensitive in children, very soon in treatment there is minimal or no tumour burden and therefore the major effect is of chemotherapy.It has been known for some years that survival time is closely related to weight loss"'and that the attendant loss of body protein is associated with increased rates of whole body protein turnover."' There have, however, been conflicting reports.'""5 The great majority of the literature is concerned with studies of adults with cancer and there are very few studies of children. An exception is two studies by Kien and Camitta,89 who, using the single dose "N-glycine technique, showed increased rates of whole body protein turnover in children with newly diagnosed leukaemia and lymphoma. Nutritional support to prevent loss of lean body mass is an integral part of treatment in cancer patients, which frequently takes the form of total parenteral nutrition. Improved nutritional status has a number of positive effects, it results in improved tolerance to chemotherapy in certain types of malignancy,"'2 improved immune competence,2"

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Phenylalanine Kinetics in Sick Preterm Neonates with Respiratory Distress Syndrome

Cited by 22 publications

References 25 publications

Uses of stable isotopes in clinical diagnosis and research in the paediatric population

Uses of stable isotopes in clinical diagnosis and research in the paediatric population

In vivo regulation of phenylalanine hydroxylation to tyrosine, studied using enrichment in apoB-100

Whole body protein metabolism in children with cancer.

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