Metabolism of 2-hydroxy-4-(methylthio)butanoate (HMTBA) in lactating dairy cows

Abstract

The objectives of the current study were to determine the fate and contribution to Met kinetics of 2-hydroxy-4-(methylthio)butanoate (HMTBA) at the whole-body, splanchnic, and mammary levels. Four multicatheterized cows (31.3 kg of milk/d; 17.7 kg of DMI/d) were used in a crossover design, with two 1-wk periods, to determine the metabolic fate of HMTBA and its effect on Met metabolism. Over the last 2 d of each period, cows were infused, via a jugular vein, with saline or HMTBA (Alimet, Novus International Inc., St. Louis, Mo) at the rate of 36 g/d. During the last 8h, the HMTBA infusion was substituted by equimolar [1-(13)C]HMTBA (8.79 mmol/h) and l[methyl-(2)H(3)]Met (1.31 mmol/h) was infused in all cows. During the last 5h, hourly samples (n=6) were collected to determine plasma flows plus the isotopic enrichments (IE) and concentrations of HMTBA ((13)C) and Met (both (13)C and (2)H(3)) in plasma from an artery plus portal, hepatic, and mammary veins. The IE of [(13)C] and [(2)H(3)]Met were also determined in milk protein taken over the last 1h of infusion in HMTBA-infused cows. The infused HMTBA increased whole-body plasma flux of Met by 6.5 mmol/h (from 17.9 to 24.4 mmol/h). Based on enrichments of (13)C-labeled Met, 3.8 mmol/h of Met flow through plasma was derived directly from HMTBA. These 2 estimates accounted for between 43 to 74% of the HMTBA dose infused, contributing to increased whole-body Met availability. Although the portal-drained viscera, liver, and mammary gland (MG) extracted 11, 37, and 3.4%, respectively, of the infused HMTBA, tissue net Met fluxes were either unchanged (portal-drained viscera, MG) or even reduced (liver: -7.9 vs. -2.4±0.6 mmol/h). Therefore, net postsplanchnic supply of Met decreased from 7.0 to 2.9 mmol/h between control and HMTBA-infused cows, compared with needs for milk protein secretion of 7.6 and 8.1 mmol/h, respectively. The HMTBA provided directly 15% of the Met required for milk protein secretion, with 0.2 mmol/h synthesized within the MG, whereas 1.1 mmol/h originated from Met produced in other tissues and transported to the MG through blood circulation. Most of the remainder needed by the MG arose from unlabeled Met released from protein breakdown in extra-splanchnic tissues and that was not reused to support intracellular protein synthesis, as this function was performed by Met synthesized from HMTBA in situ. Absorbed HMTBA, therefore, both produces and spares Met for use by the MG.

Effect of 2-hydroxy-4-methylthio-butanoic acid on ruminal fermentation, bacterial distribution, digestibility, and performance of lactating dairy cows

“…More recent data by Uchida et al (2003) and Noftsger et al (2005), however, indicated no effect of HMTBa on milk production and composition. Similarly, Rulquin et al (2006), Johnson-VanWieringen et al, (2007), and Lapierre et al (2011) did not find any production effects of HMTBa or a combination of HMTBa and Lys-HCl in cows fed basal diets with 15.3 to 19.5% CP. Similar lack of effect of HMTBa on DMI and milk yield was recently reported by Baldin 2014).…”

“…The bioavailability of HMTBa relative to that of dl-Met has been extensively studied with reports in the literature of 60 to 80% (depending on the function: BW gain, feed conversion, breast meat yield) in broiler chicken (Zelenka et al, 2013) and several meta-analyses have reported bioavailability of 81 to 100% in poultry (Vazquez-Añon et al, 2006;Vedenov and Pesti, 2010). A recent study with 13 C-labeled HMTBa infused intravenously demonstrated that the compound can serve as a source of Met and also has a Met-sparing effect in dairy cows, with 15% of the milk protein Met originating from direct conversion of HMTBa to Met (Lapierre et al, 2011).…”

Effects of addition of Aspergillus oryzae culture and 2‐hydroxyl‐4‐(methylthio) butanoic acid on milk performance and rumen fermentation of dairy cows

“…Lee et al () reported that HMB decreased dietary crude protein digestibility and increased microbial N outflow from the rumen. The study with 13 C‐labeled HMB infused intravenously showed that the Met analog can serve as a source of Met and also has a Met‐sparing effect in dairy cows, with 15% of the milk protein Met originating from direct conversion of HMB to Met (Lapierre et al ). It is inferred that HMB as a rumen‐protected Met can increase concentration of rumen MCP and milk protein potentially by releasing Met in the intestine.…”

266 Evaluation of peri-partum supplementation of methionine hydroxy analog on cow-calf performance.

“…A meta-analysis conducted by Zanton et al (2014) discovered an increase in percent milk fat due to HMTBa supplementation, but production responses to HMTBa reported in the literature varied significantly across studies. Multiple studies have indicated no effect on milk production or milk composition Lapierre et al, 2011;Lee et al, 2015), while others saw boosts in percent milk fat (Lundquist et al, 1985;Hansen et al, 1991;Baldin et al, 2018), or milk yield (Piepenbrink et al, 2004;Wang et al, 2010). The conflicting results across studies can be attributed to a variety of factors including but not limited to the level of inclusion rate of HMTBa, day of sample relative to parturition, success/failure in truly meeting daily dietary nutrient requirements, and the variation in metabolism and milk production between dairy and beef cows.…”