One Carbon Groups in Biochemistry and their role

A presentation in biochemistry regarding one carbon groups their importance and utilisation and the associated biochemical processes

1. One Carbon Groups
Generation and Utilisation

2. Definition
Some synthetic pathways require the addition of single carbon groups that exist in a
variety of oxidation states, including formyl, methenyl, methylene, and methyl. These
single carbon groups can be transferred from carrier compounds such as THF and SAM to
specific structures that are being synthesized or modified. The “one-carbon pool” refers to
the single carbon units attached to this group of carriers.

3. Examples
The one carbon groups are as Methyl (-CH3) Methylene (=CH2) Methenyl (=CH-)
Formyl (-HCO) Formimino(-CH=NH-) Hydroxy methyl (-CH2 –OH). All these one
carbon groups which are carried by folic acid

4. One-carbon units can be used for nucleotide synthesis,
methylation, and reductive metabolism, which support the high
proliferative rate of cancer cells.
Sources of One Carbon: Serine, Glycine, Histidine & Tryptophan

5. Folic acid and one-carbon metabolism
The active form of folic acid, THF, is produced from folate by
dihydrofolate reductase in a two-step reaction requiring two
nicotinamide adenine dinucleotide phosphates (NADPH). The
one-carbon unit carried by THF is bound to nitrogen N5 or N10
or to both N5 and N10. Figure 20.11 shows the structures of the
various members of the THF family and their interconversions
and indicates the sources of the one-carbon units and the
synthetic reactions in which the specific members participate.

6. Summary of the interconversions
and uses of the carrier
tetrahydrofolate

8. Propionate Pathway
Another product of cystathionine lysis, α-ketobutyrate, is converted to propionyl-CoA by α-keto
acid dehydrogenase. Propionate, methionine, threonine, isoleucine, valine, odd-chain fatty acids,
and cholesterol also contribute to propionyl-CoA production. In the mitochondria, propionyl-CoA
is first carboxylated to d-methylmalonyl-CoA by propionyl-CoA carboxylase using biotin as a
cofactor . In turn, d-methylmalonyl-CoA is epimerized to its l-stereoisomer by
methylmalonyl-CoA epimerase . l-methylmalonyl-CoA then undergoes an intramolecular
rearrangement catalyzed by the B12-dependent enzyme methylmalonyl-CoA mutase to form
succinyl-CoA, which enters the tricarboxylic acid cycle . In the absence of B12,
l-methylmalonyl-CoA forms methylmalonic acid, a robust biomarker of B12 status and 1C
metabolic function.

10. Polyamine Pathway
Ornithine is decarboxylated to the primary polyamine, putrescine, by the B6-dependent
enzyme ornithine decarboxylase. Putrescine is the precursor for spermidine and spermine
synthesis, catalyzed by aminopropylyltransferases spermidine synthase and spermine
synthase, respectively. Although ODC is typically described as the rate-limiting enzyme in
putrescine production, the supply of aminopropyl donor decarboxylated
S-adenosylmethionine is the rate-limiting factor for higher polyamine synthesis.

12. Phosphatidylcholine Pathway
SAM also plays a role in phosphatidylcholine (PC) synthesis by donating three methyl
groups to phosphatidylethanolamine (PE) via phosphatidylethanolamine methyltransferase,
an enzyme expressed principally in liver. These glycerophospholipids are most abundant
in animal tissues and are important constituents of lipoproteins in cell membranes,
facilitating lipid transport

14. Nucleotide Biosynthesis
Inosine-monophosphate (IMP) is the central intermediate for generating purines. Generation of IMP from
phosphoribosyl-pyrophosphate uses various multifunctional enzymes. Reactions catalyzed by
phosphoribosylglycinamide formyltransferase and phosphoribosylaminoimidazole carboxamide
formyltransferase provide C2 and C8 atoms for purine ring synthesis using 10-f-THF as a 1C donor. IMP
oxidation to xanthine monophosphate is the subsequent step for guanine and adenine nucleotide
biosynthesis. The central precursor for generating pyrimidines is uridine monophosphate (UMP), synthesis
of which does not require 1C cofactors. UMP is converted to deoxyuridine monophosphate (dUMP) via
uridine diphosphate by nucleoside diphosphate kinase (EC 2.7.4.6). Using 5,10-CH2-THF as the substrate,
thymidylate synthase (EC 2.1.1.45) converts dUMP to thymidine monophosphate (dTMP) by transferring
1C and is oxidized to DHF. Subsequently, DHF is reduced to THF, enclosing the metabolic loop.