title: Absorption and digestive tract metabolism of 2-hydroxy-4-methylthiobutanoic acid in lambs.
abstract: Anabolic availability of the hydroxyl methionine analog, 2-hydroxy-4-methylthiobutanoic acid (HMTBA), given as oral doses to lambs, was quantified both directly as appearance in the portal vein and as synthesis to Met by digestive tract tissues. Eight lambs, prepared with vascular catheters in the mesenteric and portal veins plus the aorta, received twice daily for 7 d either 0.46 g or 2 g of HMTBA. On d 7, [1-13C]HMTBA was supplied as 1 oral dose while [methyl-2H3]Met was infused into the jugular vein. Peak absorption as HMTBA occurred 70 to 90 min after the oral dose. All digestive tract tissues converted HMTBA to Met, equivalent to 24% of the Met provided by the diet for the larger HMTBA dose. Overall, total availability of HMBTA averaged 17.9% of the dose (range 10.6 to 27.9%), with 12.5% (range 7 to 22%) as absorbed HMBTA and the remainder as Met synthesized by digestive tract tissues. Release of 13CO2 into the portal vein accounted for another 23% of the dose. In all digestive tract tissues, the d-isomer was present in a smaller proportion than in the dose. In terms of whole-body kinetics, HMTBA loss from the plasma followed first-order kinetics, with a mean biological half-life of 76 min. Using this value, a simple model was devised to estimate HMTBA absorption based on peripheral plasma samples. When compared with direct measures of absorption, the model gave a slope of 0.81 (R2 = 0.68) and offers a practical means to test HMTBA availability to animals.
authors.affiliation: Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, UK. g.lobley@rowett.ac.uk
authors.forename: G E
authors.initials: GE
authors.lastname: Lobley
authors.forename: T J
authors.initials: TJ
authors.lastname: Wester
authors.forename: G
authors.initials: G
authors.lastname: Holtrop
authors.forename: J J
authors.initials: JJ
authors.lastname: Dibner
authors.forename: D S
authors.initials: DS
authors.lastname: Parker
authors.forename: M
authors.initials: M
authors.lastname: Vázquez-Añón
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D002247:Carbon Isotopes / Q000032:analysis; D002404:Catheterization / Q000662:veterinary; D041981:Gastrointestinal Tract / Q000378:metabolism*; D007553:Isotope Labeling; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D008962:Models, Theoretical; D011897:Random Allocation; D012756:Sheep / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium / Q000032:analysis
chemical_list: D002247:Carbon Isotopes; D014316:Tritium; C008391:alpha-hydroxy-gamma-methylmercaptobutyric acid; D008715:Methionine