Oral and intravenous l‐[1‐¹³C]phenylalanine delivery measure similar rates of elimination when gastric emptying and splanchnic extraction are accounted for in adult mixed hounds^1–4

Abstract

There are few reported estimates of amino acid (AA) kinetics in adult mammals and none exist in adult dogs. The study objectives were to evaluate the use of oral isotope delivery in contrast to the more commonly used intravenous (IV) delivery to estimate AA kinetics in adult dogs and to estimate splanchnic extraction and gastric emptying using a commonly accepted mathematical model. Dogs received 25 × 1/2-hourly meals (13 g/kg BW/day) and either an oral or IV bolus of l-[1-(13) C]Phe (12 mg/kg BW). Blood samples were taken immediately before each feeding. Concentrations of plasma Phe were measured using liquid chromatography-tandem mass spectrometry. There were no differences in baseline plasma Phe concentrations (34 μm ± 0.61), Phe distribution volume, Phe pool size and rate constants between dogs when the tracer was administered IV or orally (p > 0.25). Decay curve for plasma l-[1-(13) C]Phe differed between IV and oral dosing protocols with IV dosing fit best using a two-compartment model. Phe disappeared from plasma at a mean rate of 2.8%/min. Estimates of gastric emptying and splanchnic extraction did not differ based on oral or IV tracer dosing when the decay curves were fit with the two-compartment model (p > 0.40). The half-life for gastric emptying was 18 min, and first-pass Phe extraction by the splanchnic bed was 24% of the dietary Phe. These results suggest that oral isotope dosing can be used as an alternative to IV isotope dosing in studies that utilize a primed, constant dosing approach to measure protein and amino acid kinetics.

Whole-body phenylalanine kinetics and skeletal muscle protein signaling in horses with pituitary pars intermedia dysfunction

“…Phenylalanine intake was determined by multiplication of dietary phenylalanine intake by 0.5 to account for prececal phenylalanine digestibility 38 and the dietary phenylalanine that is extracted during first-pass splanchnic metabolism in other monogastric species. 39,40 In horses, phenylalanine is an indispensable amino acid, and de novo synthesis does not occur. Therefore, protein breakdown was estimated with the following formula:…”

Comparison of the precursor, amino acid oxidation, and end-product methods for the evaluation of protein turnover in senior dogs

“…For the calculation, only F 13 CO 2 is necessary, usually expressed as atoms percent in excess. The application of the method requires an equal body pool of phenylalanine and tyrosine in animals i.e., consuming equal amounts of these amino acids in excess of the requirement [ 52 ]. The diet used in the present study contained 0.99% phenylalanine and 0.74% tyrosine, well above the minimum requirements for these amino acids in dogs [ 53 ].…”

Splanchnic extraction of phenylalanine in mature mares was not affected by threonine supplementation

“…The differences in flux between the oral and IV infusions allowed for the calculation of phenylalanine splanchnic extraction of 26 ± 5% and 27 ± 4% for the +Thr and Basal diets, respectively. Splanchnic extraction of phenylalanine in other species ranges from 19% (Kriengsinyos et al, 2002) to 47% (Volpi et al, 1999), with most values between 20% and 30% (Volpi et al, 1999;Cvitkovic et al, 2004;Gooding et al, 2013). For future studies in horses using phenylalanine kinetics, splanchnic extraction of phenylalanine will no longer have to be estimated.…”