Methionine – roles of a key functional amino acid
Methionine (Met) is an essential amino acid and is usually the third limiting amino acid after lysine and threonine in typical swine diets. When supplying Met in swine diets it is important to consider its vital metabolic functions beyond growth performance. These include serving as a methyl donor for DNA methylation, synthesis of creatine and polyamine, and synthesis of glutathione, a major intracellular antioxidant glutathione. This function becomes increasingly important when pigs are exposed to immune challenge or heat stress conditions because glutathione is involved in the activation of T-lymphocytes and cytokines production, and in scavenging free radicals and reactive oxygen species (Wu et al., 2004; Lu, 2009).
Methionine deficiency has long-term impact on pig carcass composition
Cystine (Cys) can be converted, particularly when dietary Cys level is deficient, from Met but not vice versa. Thus, an optimal ratio of both sulfur amino acids (SAA; Met+Cys) to lysine (Lys) is usually considered for practical feed formulation. The deficiency of Met in pig diets typically results in reduced pig growth performance. For example, a feeding trial with growing pigs with initial body weight (BW) of 23.6 kg, conducted at Mississippi State University, showed that feeding a diet deficient in Met [22% below standardized ileal digestible (SID) Met + Cys requirement] but adequate in other amino acids, reduced average daily gain (ADG) (-10%) and gain:feed (G:F) ratio (-10%) compared with pigs fed a Met-adequate diet (Figure 1; Humphrey et al., 2018).
After that, all pigs were fed the same commercial grower-finisher diet for 55 days until market weight. Interestingly, pigs fed the Met-deficient diet in the early phase had similar final BW compared with their Met-adequate counterparts (122.7 vs. 122.6 kg), however, they had significantly thicker backfat (at 10th rib; 2.95 vs. 2.51 cm), heavier belly weight (11.0 vs. 9.6 kg), and lower lean gain (56.4 vs. 59.0%). These results indicate that, although compensatory growth occurs after the normal feeding, there was a long-term negative impact on carcass characteristics of pigs previously fed the Met-deficient diet.
Figure 1. Effect of dietary methionine deficiency on growth performance of growing pigs
Researchers from INRA (Conde-Aguilera et al., 2010) also reported that pigs (13.1 kg initial BW) fed a Met-deficient diet (0.20% SID Met) for 19-days had a lower final BW and a higher lipid deposition than the pigs fed a Met-adequate diet (0.45% SID Met). The intriguing finding was that the content of Met and Glu was higher and Ile content tended to be higher, while His content was lower in the empty body of pigs fed the Met-adequate diet relative to pigs fed the Met-deficient diet (Figure 2). This was not in line with the current assumption of a constant ideal amino acid ratio to express amino acid requirement for body protein accretion. These results indicate that a deficient Met supply affects the amino acid composition of body proteins, reduces lean gain and increases body fat which is not desired from the consumer and carcass grading standpoints.
Methionine requirement is increased when pigs are fed antibiotic-free diets
In intensive pig production facilities, subclinical levels of immune system stimulation (ISS), induced by pathogenic microorganisms, occur frequently. This type of immune stimulation modifies amino acids utilization by redirecting away from growth towards production of immune tissues, such as acute phase proteins (APP) and glutathione.
During immune challenge, the gastrointestinal tract (GIT) – a key component of the body's systemic immune system – undergoes morphological and physiological changes associated with increased mucin production. The GIT also serves as a home for various microbes, which synthesize and utilize amino acids. For example, as much as 50% of dietary Met is utilized by the first pass metabolism of the portal-drained viscera (small and large intestine, stomach, pancreas and spleen) in pigs (Stoll et al., 1998). Dai et al. (2010), in a cell culture study, found that 23% of Met supply in inoculum solution was utilized for bacterial protein synthesis. These results indicate that Met is also required for maintenance of gut epithelial cells and microbial balance in the gut.
During the immune challenge, utilization of Met+Cys to produce compounds involved in the immune response, such as glutathione and taurine, is increased (Grimble, 2002). A recent study with piglets, Rasch et al. (2019) found that supplementation with DL-Met or L-Met to a Met-deficient diet increases the transsulfuration rate of Met to form Cys and consequently glutathione. Indeed, the need for Met+Cys to be supplied in the diet increases during the immune challenge situation. Rakhshandeh et al. (2014) reported that the immune challenge by injection of lipopolysaccharide (LPS) reduced body protein deposition but increased maintenance requirement for Met+Cys. They estimated that normal pigs need 1.63 g SID Met+Cys intake, while immune challenged pigs need 1.87 g SID Met+Cys intake to achieve the same body protein deposition of 50 g/d, which is an increase by 15% (Figure 3).
Figure 3. Impact of immune system stimulation (ISS) and standardized ileal digestible (SID) SAA intake on body protein deposition in growing pigs
Antibiotic growth promoters (AGPs) have been added in pig and poultry diets to maintain gut health and to minimize infections. A higher stimulation of the immune system and a higher endogenous protein loss were observed after the ban of AGPs in animal feeds in the European Union (Roth et al., 1999). This means that pigs fed with AGP-free diets and raised under commercial conditions may be more susceptible to immune challenges. As increasing number of countries are banning APGs in animal diets, it is important to recheck the Met+Cys requirements for pigs fed AGP-free diets and raised under commercial conditions.
A study conducted in the Netherlands showed that the ADG, average daily feed intake (ADFI), and G:F for 8 to 20 kg pigs infected with E. coli and fed AGP-free diets were optimized at the SID Met+Cys:Lys ratios of 71, 73, and 68%, respectively (Capozzalo et al., 2017a). Similarly, the dietary SID Met+Cys:Lys ratio to maximize body protein deposition increases from 55 to 75% when growing pigs are immune challenged with LPS and fed AGP-free diets (Kim et al., 2012).
Table 1. Effect of dietary SID Met+Cys:Lys ratio on the performance of growing pigs
A study conducted under commercial conditions in China also showed that ADG and feed conversion ratio (FCR) of growing pigs were optimized at a SID Met+Cys:Lys ratio of 63% (Zhang et al., 2015; Table 1), which is higher than the current NRC (2012) recommendation of 56%. Using a 2 x 2 factorial arrangement [(52 vs. 60% SID SAA:Lys) x (16 vs. 24% SID Trp:Lys)], a 14-day trial conducted in Australia showed that ADG and FCR of E. coli challenged weaned pigs were optimized when the AGP-free diet contained 24% SID Trp:Lys and 60% SID Met+Cys:Lys ratio (Capozzalo et al., 2017b; Figure 4).
Figure 4. Effect of dietary tryptophan and sulphur amino acids levels on performance of weaned pigs challenged with E. coli
In a nitrogen balance study with growing pigs, immune challenge (LPS injection) reduced protein deposition rate but the optimal dietary Met to Met+Cys ratio to maximize body protein deposition increased from 57 to 59% (Litvak et al., 2013; Figure 5). These results indicate that the needs of Met+Cys, including the Met requirement for converting to Cys, are increased during immune challenge conditions.
Figure 5. Effect of immune challenge and Met:Met+Cys ratios on body protein deposition
A recent Chinese trial with 130 multiparous sows evaluated the effect of graded level of Met:Lys ratios in AGP-free diets, starting from 1 day before parturition until weaning (day 21 of lactation) on performance of sows and piglets (Wei et al., 2019). Although the overall performance of sows was not affected, increasing the dietary SID Met:Lys ratio from 37 to 57% in the lactation diet increased average BW of piglets at weaning, and the blood concentrations of taurine and glutathione (Table 2).
Table 2. Effect of Met:Lys ratio in the lactation diet on the performance of sows and piglets
Overall, these results indicate that the requirement of Met+Cys, including the Met requirement for converting to Cys, is increased when pigs are fed AGP-free diets under commercial conditions or during immune challenge.
Methionine, a dietary essential amino acid, plays critical roles not only for protein synthesis but also in various important metabolic functions. As a precursor for the synthesis polyamine and glutathione, the requirement or optimal ratio of Met+Cys:Lys is increased under immune challenge conditions as well as for pigs fed AGP-free diets and raised under commercial conditions. Recent studies suggest that the SID Met+Cys:Lys ratio should be at least 60 and 63% in diets for weaned pigs and growing pigs, respectively to maintain gut barrier function and maximize growth performance. The impact of immune status on Met+Cys requirement should be considered when formulating diets for pigs.
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Article made possible through the contribution of Dr. Ing John Htoo and Evonik Nutrition & Care GmbH