Human [74Se]selenomethionine metabolism: a kinetic model

Swanson, Christine A.; Patterson, Blossom H.; Levander, Orville A.; Veillon, Claude; Taylor, Philip R.; Helzlsouer, Kathy J.; McAdam, P A; Zech, Loren A.

doi:10.1093/ajcn/54.5.917

Cited by 125 publications

(94 citation statements)

References 19 publications

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“…This assumption is certainly not in line with the true kinetics as the tracer will leave the body after a while. However, for the observed 2 h of study, this is in agreement with the findings of Swanson et al (7) and Wastney et al (8) . In their studies, the level of the tracer in plasma was consistently rising during the first couple of hours, and it did not start to decrease before approximately 3 h after administration.…”

Section: Discussionsupporting

confidence: 92%

“…Currently, our understanding of Se absorption, whole-body retention and excretion is based on whole-body counting (5) or balance and tracer studies (6)(7)(8) . Data from previous studies (13)(14)(15) indicate a fundamental complexity of Se metabolism that can be explained by several factors.…”

Section: Discussionmentioning

confidence: 99%

“…We found that when restricting the investigation of kinetics to the first 2 h after SeMet administration, the dynamics of the data can be captured by a considerably simpler model as compared with the more complex models, which previously have been employed to describe Se metabolism (7,8) . The reason for this may be 2-fold.…”

Section: Discussionmentioning

confidence: 99%

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Absorption and initial metabolism of ⁷⁵Se-l-selenomethionine: a kinetic model based on dynamic scintigraphic data

et al. 2015

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Selenomethionine (SeMet) is an important organic nutritional source of Se, but the uptake and metabolism of SeMet are poorly characterised in humans. Dynamic gamma camera images of the abdominal region were acquired from eight healthy young men after the ingestion of radioactive 75 Se-L-SeMet ( 75 Se-SeMet). Scanning started simultaneously to the ingestion of 75 Se-SeMet and lasted 120 min. We generated timeactivity curves from two-dimensional regions of interest in the stomach, small intestine and liver. During scanning, blood samples were collected at 10-min intervals to generate plasma time-activity curves. A four-compartment model, augmented with a delay between the liver and plasma, was fitted to individual participants' data. The mean rate constant for 75 Se-SeMet transport was 2·63 h -1 from the stomach to the small intestine, 13·2 h -1 from the small intestine to the liver, 0·261 h -1 from the liver to the plasma and 0·267 h -1 from the stomach to the plasma. The delay in the liver was 0·714 h. Gamma camera imaging provides data for use in compartmental modelling of 75 Se-SeMet absorption and metabolism in humans. In clinical settings, the obtained rate constants and the delay in the liver may be useful variables for quantifying reduced intestinal absorption capacity or liver function.Key words: Selenomethionine: 75 Se-L-selenomethionine: Absorption capacity: Metabolism: Gamma camera imaging: Compartmental modelling Selenomethionine (SeMet) is an important organic nutritional source of Se (1,2) . Absorption of various Se compounds occurs via different routes and mechanisms. Membrane transport of selenoamino acids, including SeMet, involves a specific suite of amino acid transporters (3) . The subsequent incorporation of dietary Se into selenoproteins occurs through a series of interconversions, of which many details remain unknown. Se metabolites are excreted in the urine and faeces and in exhaled air, mainly as selenosugars and methylated compounds (4) .The initial metabolism of Se in humans is poorly characterised. Estimates of Se absorption, whole-body retention and excretion have been made predominantly on whole-body counting (5) or the recovery of ingested tracers in the blood, urine and faeces (6) . Compartmental analyses of kinetic data from tracer studies have also been used to create a more integrated picture of whole-body Se utilisation in humans (7,8) . These studies characterised the long-term kinetics by the investigation of urine and faecal data collected over 12 d and blood samples drawn over 4 months. Through detailed mathematical modelling including several plasma pools, they were able to provide new insights into the long-run Se metabolism. However, because the study data only comprised hourly observations after dose administration, the initial Se kinetics could not be investigated and therefore still remained unclear. Our study tries to fill this gap and to provide deeper insight into the initial Se kinetics by focusing on frequent data collection within the first 2 h after a...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Absorption and initial metabolism of ⁷⁵Se-l-selenomethionine: a kinetic model based on dynamic scintigraphic data

et al. 2015

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“…This reflects nonspecific incorporation of seleno amino acids into general protein synthesis compared with specific incorporation of inorganic forms of selenium into seleno protein synthesis. At normal intakes, urine is the most important route of excretion of selenium and regulates homeostasis (Swanson et al, 1991) although there is some evidence that prolonged high intakes of organic forms of selenium such as selenomethionine may accumulate in the body due to the relatively slow turnover of this amino acid incorporated into general protein synthesis . Retention of selenium from yeast was lower than the retention value found in fish but higher than the retention of selenate and supports the suggestion made earlier that the yeast probably had a mixture of significant amounts of inorganic and organic selenium present in the cell.…”

Section: Discussionmentioning

confidence: 99%

Bioavailability of selenium from fish, yeast and selenate: a comparative study in humans using stable isotopes

et al. 2004

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Objective: To measure the bioavailability of selenium from cooked and raw fish in humans by estimating and comparing apparent absorption and retention of selenium in biosynthetically labelled fish with labelled selenate and biosynthetically labelled selenium in brewers yeast. Design: The intervention study was a parallel, randomised, reference substance controlled design carried out at two different centres in Europe. Setting: The human study was carried out at the Institute of Food Research, Norwich, UK and at TNO Nutrition and Food Research, Zeist, The Netherlands. Subjects: In all, 35 male volunteers aged 18-50 y were recruited; 17 subjects were studied in Norwich (UK) and 18 in Zeist (Netherlands). All of the recruited subjects completed the study. Interventions: Biosynthetically labelled trout fish (processed by two different methods), biosynthetically labelled brewers yeast and isotopically labelled selenate were used to estimate selenium apparent absorption and retention by quantitative analysis of stable isotope labels recovered in faeces and urine. Subjects consumed the labelled foods in four meals over two consecutive days and absorption was measured by the luminal disappearance method over 10 days. Urinary clearance of isotopic labels was measured over 7 days to enable retention to be calculated. Results: Apparent absorption of selenium from fish was similar to selenate and there was no difference between the two processing methods used. However, retention of fish selenium was significantly higher than selenate (Po0.001). Apparent absorption and retention of yeast selenium was significantly different (Po0.001) from both fish selenium and selenate. Conclusion: Fish selenium is a highly bioavailable source of dietary selenium. Cooking did not affect selenium apparent absorption or retention from fish. Selenium from yeast is less bioavailable.

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“…They conclude that ageing has no effect on Se status. A SeMet model was published by Swanson et al (1991) and was based on six adults consuming an oral dose of 200 µg 74 Se as L-SeMet. It was developed from the selenite model of Patterson et al (1989) but contains some differences.…”

Section: Studiesmentioning

confidence: 99%

Use of stable isotopes and mathematical modelling to investigate human mineral metabolism

Dainty

2001

nutr res rev

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Individuals have varying needs for minerals that are dependent, amongst other things, on their lifestyle, age and genetic makeup. Knowledge of exact individual nutritional requirements should lead to better health, increased quality of life and reduced need for expensive medical care. Bioavailability, nutrient-gene interactions and whole-body metabolism all need to be investigated further if we are to progress towards the goal of defining optimal health and nutritional status. The discussion which follows will critically review the latest developments in the area of metabolism for several of the minerals that are essential for human health: Ca, Zn, Cu and Se. Stable-isotope tracers and mathematical modelling are some of the tools being used to facilitate the greater understanding in uptake, utilisation and excretion of these minerals. Stable isotopes, administered in physiological doses, present little or no risk to volunteers and allow metabolic studies to be carried out in vulnerable population groups such as children and pregnant women. Intrinsic labelling of foodstuffs ensures that the tracer and the native mineral will behave similarly once inside the body. Advances in computing power and software dedicated to solving nutritional problems have made it possible for investigators to use mathematical modelling in their experimental work. Mineral metabolism is ideally suited to a form of modelling known as compartmental analysis, which allows rates of mineral transfer and sizes of mineral stores to be calculated accurately without the need for invasive sampling of body tissues. Stable isotopes: Mathematical modelling: Mineral metabolismNutrition Research Reviews (2001) , IntroductionMost minerals have several naturally-occurring stable isotopes, all with a fixed abundance. In order to follow the metabolism of a mineral, it is necessary to ingest it in an altered form so that it can be distinguished from the naturally-abundant mineral. The form of the ingested mineral can be altered by enriching one of the low-abundance isotopes. This so-called 'tracer' or 'label' is injected and/or taken orally and its appearance in the plasma, urine and faeces can be monitored over several days. The concept of a tracer is important in isotope work. A true tracer is one that does not perturb the system it is investigating. Only radioisotopes can be called true tracers, since they are administered in extremely small quantities. The term 'label' is more appropriate for stable isotopes, since they are usually given in quantities equivalent to the amount received in the normal diet. The word 'tracer' is, however, still used in some stable-isotope studies with the implicit understanding that it will almost certainly perturb the system under investigation. The underlying assumption in this type of work is that the label (or tracer) behaves in the same kinetic way as the naturally-abundant mineral (sometimes called the tracee), otherwise the use of labels to mimic the behaviour of the native mineral is invalid. There must be no discri...

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Human [74Se]selenomethionine metabolism: a kinetic model

Cited by 125 publications

References 19 publications

Absorption and initial metabolism of ⁷⁵Se-l-selenomethionine: a kinetic model based on dynamic scintigraphic data

Absorption and initial metabolism of ⁷⁵Se-l-selenomethionine: a kinetic model based on dynamic scintigraphic data

Bioavailability of selenium from fish, yeast and selenate: a comparative study in humans using stable isotopes

Use of stable isotopes and mathematical modelling to investigate human mineral metabolism

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Human [74Se]selenomethionine metabolism: a kinetic model

Cited by 125 publications

References 19 publications

Absorption and initial metabolism of 75Se-l-selenomethionine: a kinetic model based on dynamic scintigraphic data

Absorption and initial metabolism of 75Se-l-selenomethionine: a kinetic model based on dynamic scintigraphic data

Bioavailability of selenium from fish, yeast and selenate: a comparative study in humans using stable isotopes

Use of stable isotopes and mathematical modelling to investigate human mineral metabolism

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Absorption and initial metabolism of ⁷⁵Se-l-selenomethionine: a kinetic model based on dynamic scintigraphic data

Absorption and initial metabolism of ⁷⁵Se-l-selenomethionine: a kinetic model based on dynamic scintigraphic data