One carbon enzyme systems Serine hydroxymethyltransferase (SHMT) and Glycine cleavage complex (GCV)

Serine hydroxymethyltransferase (SHMT) is the enzyme which catalyses the conversion of serine to glycine and vice versa. This enzyme provides the capability of de novo glycine biosynthesis. This capability is present in all apicomplexans including Plasmodium Toxoplasma, Cryptosporidium and Theileria species [1]. In addition, it is important to folate metabolism as this glycine biosynthesis also leads to synthesis of 5,10-methylene-tetrahydrofolate, an essential substrate of thymidylate synthase enzyme (catalyses generation of thymidine nucleotides). The characterisation, expression and kinetic studies with P. falciparum SHMT demonstrates that it is a regulatory step of thymidylate cycle and serves a good drug target [2]. Glycine cleavage system is a system of four proteins and they are P-protein, T-protein, L-protein and H-protein. When glycine is in excess, the first three proteins catalyse three enzymatic steps and H-protein acts as an aminomethyl-group carrier. This set of reactions generates carbon dioxide, ammonia and 5,10-methylene-THF utilising glycine and tetrahydrofolate as substrates. In addition, glycine cleavage systsm transfers electrons to NAD+ generating NADH. In plants, glycine cleavage system is coupled to SHMT [3]. P. falciparum has two isoforms of SHMT, one localised primarily to cytosol and other to mitochondrion [4]. Piroplasma species have one isoform of SHMT as in T. gondii. As Plasmodium is auxotrophic to serine [1], it may catalyse serine biosynthesis when glycine is in excess (from haemoglobin digestion) and SHMT may be coupled to glycine cleavage system (MPMP SHMT and GCV pathway). This might also be true for Piroplasma species as they are auxotrophic to serine.

 

Enzyme EC Number Gene id
Glycine dehydrogenase (P-protein) 1.4.4.2 Missing in annotation
Dihydrolipoamide dehydrogenase  (L-protein) 1.8.1.4 TP03_0227
Serine hydroxymethyltransferase (SHMT) 2.1.2.1 TP01_0390
Aminomethyltransferase (T-protein) 2.1.2.10 TP01_0480
Aminomethyltransferase (T-protein) 2.1.2.10 TP01_0521
H-protein-lipoyllysine (H-protein) none TP02_0234

 

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