Twenty-four–hour intravenous and oral tracer studies with L-[1-13C]-2-aminoadipic acid and L-[1-13C]lysine as tracers at generous nitrogen and lysine intakes in healthy adults

El-Khoury, Antoine E.; Basile, Anibal; Beaumier, Louis; Wang, San Y; Al-Amiri, Hanan; Selvaraj, Ambalini; Wong, Sue; Atkinson, Alan; Ajami, Alfred M.; Young, Vernon R.

doi:10.1093/ajcn/68.4.827

Cited by 27 publications

(2 citation statements)

References 36 publications

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“…Whole body leucine oxidation broadly followed the changes in arterial plasma leucine concentration over time for each group of cows (Figure 1). This type of association has been reported previously in humans for leucine (El-Khoury et al, 1994) and for lysine (El-Khoury et al, 1998). Availability of tissue free amino acids would be an important determinant of their oxidation rate.…”

Section: Whole Body Leucine Kinetics Using Plasma As the Precursor Poolsupporting

confidence: 82%

Variations in Mammary Protein Metabolism During the Natural Filling of the Udder with Milk over a 12-h Period Between Two Milkings: Leucine Kinetics

Thivierge

Petitclerc

Bernier

et al. 2002

Journal of Dairy Science

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To define the temporal variations of whole body and mammary leucine kinetics over a 12-h period between two milkings, we used two groups of four Holstein cows, one in their second and the other in their third or fourth lactation. Cows were infused with L-[1-13C]leucine during the 12-h interval between two milkings. Blood was sampled every 30 min during that period from arterial and mammary sources. Timeafter milking did not affect whole body irreversible loss rate of leucine but affected whole body leucine oxidation, which broadly followed variations in arterial plasma leucine concentration. Similarly, mammary leucine irreversible loss rate and leucine used for protein synthesis were not affected by time after milking. Leucine oxidation by the mammary gland was, however, affected by time after milking. It increased by 15% from the first 2-h period to the following 4-h period and then decreased by 13% over the following 2-h period. A 21% increase in leucine oxidation was observed from 8 to 10 h after milking, and then it decreased by 26% over the last 2-h period. Protein degradation expressed as percentage of mammary leucine flux followed a similar temporal pattern. Leucine used for protein synthesis by the mammary gland was unaltered over time after milking, suggesting that the increased availability of leucine resulting from mammary protein breakdown would increase intracellular concentrations of leucine, which would have favored its catabolism. Overall, these results confirm the high metabolic activity of the mammary gland, as protein synthesis by the mammary gland averaged 43% of whole body protein synthesis.

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Section: Whole Body Leucine Kinetics Using Plasma As the Precursor Poolsupporting

confidence: 82%

Variations in Mammary Protein Metabolism During the Natural Filling of the Udder with Milk over a 12-h Period Between Two Milkings: Leucine Kinetics

Thivierge

Petitclerc

Bernier

et al. 2002

Journal of Dairy Science

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“…Intravenous clinical data are not only useful in the determination of absolute bioavailability for regulatory submission of NCEs but can also be applied to measuring the kinetics of constitutive metabolites along the route of biochemical pathways. Isotopic methods for measuring the metabolic incorporation of constitutive components are well established, for example, using 13 C and 2 H . The addition of a microtracer approach enhances the study by enabling the intravenous administration of the isotopic tracer to humans at potentially very low levels.…”

Section: Sitosterolmentioning

confidence: 99%

Approaches to intravenous clinical pharmacokinetics: Recent developments with isotopic microtracers

Lappin

2015

The Journal of Clinical Pharmacology

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Obtaining pharmacokinetic data from the intravenous route for drugs intended for oral administration has traditionally been expensive and time consuming because of the toxicology requirements and challenges in intravenous formulations. Such studies are necessary, however, particularly when regulator agencies request absolute bioavailability data. A method has emerged whereby the drug administered intravenously is isotopically labeled and dosed at a maximum of 100 µg concomitantly with an oral administration given at a therapeutically relevant level. The intravenous administration has been termed a microtracer and obviates intravenous toxicology requirements as well as simplifying formulations. The study design also essentially removes issues of nonlinear pharmacokinetics that may occur when oral and intravenous doses are administered separately. This review examines the methodology and the literature to date, including those studies intended for regulatory submission. The method has been extended to the study of prodrug-to-active drug kinetics and to obtaining clearance, volume of distribution, and absolute bioavailability at steady-state conditions.

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Amino Acids and Nitrogen Compounds

Kohlmeier¹

2015

Nutrient Metabolism

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Twenty-four–hour intravenous and oral tracer studies with L-[1-13C]-2-aminoadipic acid and L-[1-13C]lysine as tracers at generous nitrogen and lysine intakes in healthy adults

Abstract: ABSTRACT

Cited by 27 publications

References 36 publications

Variations in Mammary Protein Metabolism During the Natural Filling of the Udder with Milk over a 12-h Period Between Two Milkings: Leucine Kinetics

Variations in Mammary Protein Metabolism During the Natural Filling of the Udder with Milk over a 12-h Period Between Two Milkings: Leucine Kinetics

Approaches to intravenous clinical pharmacokinetics: Recent developments with isotopic microtracers

Amino Acids and Nitrogen Compounds

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