Formaldehyde serine hydroxymethyltransferase

L-serine glycine + formaldehyde serine hydroxymethyltransferase E. coli 201... 

Side chain cleavage (Group c). In a third type of reaction the side chain of the Schiff base of Fig. 14-5 undergoes aldol cleavage. Conversely, a side chain can be added by (3 condensation. The best known enzyme of this group is serine hydroxymethyltransferase, which converts serine to glycine and formaldehyde.211-21313 The latter is not released in a free form but is transferred by the same enzyme specifically to tetrahydrofolic acid (Eq. 14-30), with which it forms a cyclic adduct. 

The pyridoxal-5 -phosphate dependent serine hydroxymethyltransferase (SHMT EC 2.1.2.1) in vivo catalyzes the interconversion of L-serine 158 and glycine 149 by transfer of the /1-carbon of L-serine to tetrahydrofolate (THF) by which the activated formaldehyde is physiologically made available as a C,-pool. The reaction is fully reversible and provides a means for the stereoselective synthesis of 158 in vitro from donor 149 and formaldehyde. Economical yields (88-94%) of L-serine have thus been obtained on a multimolar scale using raw cell extracts of recombinant Klebsiella aerogenes or E. coll in a controlled bioreactor at final product concentrations > 450 gl 1 [461,462], Several SHMTs have been purified and characterized from various organisms including animal tissues [463,464], eucaryotic [465] and procaryotic... 

C((x)-C(p) bond cleavage in a-amino acids is precedented by the PLP-containing enzyme serine hydroxymethyltransferase, interconverting serine with glycine and a formaldehyde equivalent, but in that case C-C bond cleavage is a retro aldol process This route is not obviously open to ACPC (9). 

Glycine (Gly, G) is generated from serine (Ser, S) by the loss of the elements of formaldehyde (CH2O) that is, while it is possible that formaldehyde is actually formed in situ, it is considered unhkely as a free species and so the enzyme catalyzing this process, glycine hydroxymethyltransferase (EC 2.1.2.1), has both pyridoxal and tetrahydrofolate in close proximity in the active site. As shown in Scheme 12.9, pyridoxal-coordinated serine (Ser,S) loses the equivalent of formaldehyde ( CH2O ) to the cofactor tetrahydrofolate to produce 5,10-methylenetetrahydrofolate, a species utilized as a source of methylene units for methylation of other intermediates. 

---