Gene expression differences in the methionine remethylation and transsulphuration pathways under methionine restriction and recovery with D,L‐methionine or D,L‐HMTBA in meat‐type chickens

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L‐methionine (L‐Met) is an essential amino acid that is required for protein synthesis and also plays an essential role in the metabolism of S‐adenosyl methionine (SAM). SAM depletion has been associated with colon and breast cancers, liver diseases and pathogenic brain function such as depression and Alzheimer's (Zhuo et al., 2010). L‐methionine is converted to SAM which then serves primarily as the sole methyl donor to a variety of molecules including nucleic acids, proteins, DNA CpG islands and biological amines (Mato, Alvarez, Ortiz, & Pajares, 1997). The conversion of L‐Met to SAM is catalysed by methionine adenosyltransferases (MATs). SAM is converted to S‐adenosyl‐L‐homocysteine (SAH) by a reaction catalalysed by an enzyme encoded by the glycine N‐methyltransferase (GNMT) gene. SAH is subsequently hydrolysed to homocysteine (Hcy): cellular thiol by an enzyme encoded by the AHCY gene. The SAM/SAH ratio defines the methylation potential of a tissue (Luka, Mudd, & Wagner, 2009; Mato & Lu, 2007).
Homocysteine is a metabolic hub that can be remethylated to L‐Met or enter the transsulphuration pathway to form other thiol products such as cysteine (Cys), glutathione (GSH) and taurine (Finkelstein, 1998; Mangge, Becker, Fuchs, & Gostner, 2014; Mato et al., 1997; Selhub & Miller, 1992). Decarboxylated SAM also plays an important role in the synthesis of polyamines via the aminopropylation pathway. Inhibition of polyamine synthesis severely affects cell growth (Pegg, 2009). SAM is also the precursor of Hcy (Finkelstein, 1998). Homocysteine can be remethylated to form L‐Met by receiving methyl from 5‐methyltetrahydrofolate (5‐methyl‐THF) with vitamin B12 as a cofactor. An additional tissue‐specific vitamin B12 independent route for Hcy remethylation is catalysed by the zinc‐dependent BHMT that utilises betaine as a methyl donor (Finkelstein, 1998; Stipanuk & Ueki, 2011). Homocysteine can also be irreversibly converted to Cys via the transsulphuration pathway where it condenses with serine to form cystathionine, a reaction catalysed by cystathionine β‐synthase (CBS) followed by a conversion to Cys by cystathionine [Latin Small Letter Gamma]‐lyase (Finkelstein, 1998; Mendes et al., 2014; Stipanuk & Ueki, 2011). Thus, exploration of the methionine pathway is a possible way to ameliorate changes in dietary methionine levels.
Methionine is also the first‐limiting amino acid in a typical corn‐soy poultry diet. Suboptimal levels of dietary Met have been documented to impair growth, feed efficiency (Garber & Baker, 1971; Lepore, 1965; Willemsen et al., 2011) and compromise the immune status of the bird (Tsiagbe, Cook, Harper, & Sunde, 1987; Wu et al., 2013; Zhang & Guo, 2008). Deficient poultry diets are supplemented with synthesized D,L‐methionine (D,L‐Met) or one of its analogues, 2‐hydroxy‐4‐(methylthio)butanoic acid (D,L‐HMTBA). Both D,L‐Met and D,L‐HMTBA are converted within the body into the biologically active L‐Met (Dibner & Knight, 1984).
Despite current knowledge on the role of Met in growth, feed efficiency and body composition, the underlying molecular mechanisms and networks associated with Met metabolism remain to be elucidated. An understanding of the molecular regulatory mechanisms of Met is essential to optimise its dietary requirements under various production environments.
We hypothesise that the molecular mechanisms that underlie the remethylation and transsulphuration pathways during Met restriction and recovery with D,L‐Met or D,L‐HMTBA may be different.
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