levels through: (1) allosteric and transcriptional regulations of the amino acid
pathway derived from aspartate (Fig. 2), (2) translational and posttranscriptional
regulation of methionine adenosyltransferase, (3) transmethylation reactions,
(4) regeneration via the methyl cycle and Yang cycle, and (5) elevated shuttling of
AdoMet into several biosynthetic pathway such as ethylene and polyamines
(Bürstenbinder et al. 2007; Van de Poel et al. 2012). Because AdoMet is synthesized
in the cytosol, its availability for plastidial reactions therefore requires a specific
carrier, which is another regulatory point for AdoMet homeostasis (Fig. 3). In this
respect, in Arabidopsis a chloroplastic AdoMet carrier was able to catalyze the
unidirectional import of cytosolic AdoMet as well as the exchange between a
cytosolic AdoMet and a chloroplastic AdoMet or S-adenosylhomocysteine (Ravanel
et al. 2004). Therefore, because of its cellular importance, AdoMet requires two
salvage pathways to regenerate its adenosine moiety, methylthio-group and methyl
group used in methylation reactions.
3.1 A Methyl Cycle Serves to Regenerate the Methyl Group
Issued from AdoMet
The S-adenosylhomocysteine (AdoHcy) issued from methylation reactions with
AdoMet can be recycled to methionine from the homocysteine (Hcy) intermediate
through the methyl or AdoMet cycle (Ravanel et al. 1998). AdoHcy issued from
transmethylation reactions is converted into Hcy by AdoHcy hydrolase and Hcy
is then regenerated to methionine by Met synthase (Fig. 3). Conversion of homocysteine into methionine can occur in mitochondria, chloroplasts, and cytosol
(Clandinin and Cossins 1974; Shah and Cossins 1970; Eichel et al. 1995).
The last two steps of this cycle are assumed to occur mainly in the cytosol (Hanson
and Roje 2001; Roje et al. 2002a), since an AdoMet carrier is involved to ensure
the exchanges between cytosolic and chloroplastic AdoMet or SAH (Ravanel et al.
2004). Met synthase catalyzes methionine formation and simultaneously allows
regeneration of the methyl group of AdoMet via the use of a folic compound:
5-CH3H4PteGlu(n) (Cossins 1987; Roje et al. 2002b). The carbon of the methyl
group provided by the folic compound originates from the β-carbon of serine
(Fig. 3). The methyl cycle is fine-tuned by SAH levels, inhibiting folate compound
biosynthesis through MTHFR (Jencks and Mathews 1987; Roje et al. 2002b) and by
high levels of AdoMet that reduce methionine production (Crider et al. 2012).
In summary, the methyl-group transfer catalyzed by AdoMet in methylation reactions is directly provided from serine through folates (vitamins B 9 ) that serve as
donors or acceptors in one-carbon (C1 metabolism) transfer reactions. In other
words, AdoMet is used by folates as a relay molecule to extend their capacities for
From Aspartate to Ethylene: Central Role of N, C, and S Shuttles by. . .
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pathway derived from aspartate (Fig. 2), (2) translational and posttranscriptional
regulation of methionine adenosyltransferase, (3) transmethylation reactions,
(4) regeneration via the methyl cycle and Yang cycle, and (5) elevated shuttling of
AdoMet into several biosynthetic pathway such as ethylene and polyamines
(Bürstenbinder et al. 2007; Van de Poel et al. 2012). Because AdoMet is synthesized
in the cytosol, its availability for plastidial reactions therefore requires a specific
carrier, which is another regulatory point for AdoMet homeostasis (Fig. 3). In this
respect, in Arabidopsis a chloroplastic AdoMet carrier was able to catalyze the
unidirectional import of cytosolic AdoMet as well as the exchange between a
cytosolic AdoMet and a chloroplastic AdoMet or S-adenosylhomocysteine (Ravanel
et al. 2004). Therefore, because of its cellular importance, AdoMet requires two
salvage pathways to regenerate its adenosine moiety, methylthio-group and methyl
group used in methylation reactions.
3.1 A Methyl Cycle Serves to Regenerate the Methyl Group
Issued from AdoMet
The S-adenosylhomocysteine (AdoHcy) issued from methylation reactions with
AdoMet can be recycled to methionine from the homocysteine (Hcy) intermediate
through the methyl or AdoMet cycle (Ravanel et al. 1998). AdoHcy issued from
transmethylation reactions is converted into Hcy by AdoHcy hydrolase and Hcy
is then regenerated to methionine by Met synthase (Fig. 3). Conversion of homocysteine into methionine can occur in mitochondria, chloroplasts, and cytosol
(Clandinin and Cossins 1974; Shah and Cossins 1970; Eichel et al. 1995).
The last two steps of this cycle are assumed to occur mainly in the cytosol (Hanson
and Roje 2001; Roje et al. 2002a), since an AdoMet carrier is involved to ensure
the exchanges between cytosolic and chloroplastic AdoMet or SAH (Ravanel et al.
2004). Met synthase catalyzes methionine formation and simultaneously allows
regeneration of the methyl group of AdoMet via the use of a folic compound:
5-CH3H4PteGlu(n) (Cossins 1987; Roje et al. 2002b). The carbon of the methyl
group provided by the folic compound originates from the β-carbon of serine
(Fig. 3). The methyl cycle is fine-tuned by SAH levels, inhibiting folate compound
biosynthesis through MTHFR (Jencks and Mathews 1987; Roje et al. 2002b) and by
high levels of AdoMet that reduce methionine production (Crider et al. 2012).
In summary, the methyl-group transfer catalyzed by AdoMet in methylation reactions is directly provided from serine through folates (vitamins B 9 ) that serve as
donors or acceptors in one-carbon (C1 metabolism) transfer reactions. In other
words, AdoMet is used by folates as a relay molecule to extend their capacities for
From Aspartate to Ethylene: Central Role of N, C, and S Shuttles by. . .
263