Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

114 Chapter 5
to these atoms that the one-carbon unit is attached, and there are several
diVerent forms of the cofactor, illustrated in Figure 5.43.
The mechanism for transfer of a methylene or methyne involves nucleophilic
attack on the imine formed between the one-carbon unit and either N 5 or
N 10 , followed by breakdown of the substrate–coenzyme intermediate. An
example is the formation of 5-hydroxymethylcytidine from cytidine, which is
illustrated in Figure 5.44.
How is methylene-tetrahydrofolate synthesised in the cell Not from free
formaldehyde, which is toxic to biological systems. Conversion of tetrahydrofolate
to methylene-tetrahydrofolate is carried out by serine hydroxymethyltransferase,
a pyridoxal phosphate-dependent enzyme which we shall meet in
Section 9.5. SuYce it to say that it is the hydroxymethyl group of serine which is
transferred, generating glycine as a by-product. Methyne-tetrahydrofolate can
be synthesised either by the NADP-dependent oxidation of methylene-tetrahydrofolate,
or it can be synthesised by a synthetase enzyme which uses formyl
phosphate as an activated one-carbon equivalent, generated from formate by
ATP (see Figure 5.45).
H 2 N
HN
N
H
N
5
N
H
O HN 10 O
HN
CO 2
−
O
n
O −
FH 4
N 5 -Methyl-FH 4
N 5 ,N 10 -Methylene-FH 4 N 5 ,N 10 -Methyne-FH 4
N
N
H
HN CH
HN 3
CH 2
HN
N
CH 2 N
+
N
CH
+
N
N
Figure 5.43 Tetrahydrofolate and its one-carbon adducts.