The One-Carbon Units include different groups linked to THF:
Details of folate Pathways
They are produced during the metabolism of some Aminoacids, namely:
- Histidine (via N-formimidoyl-L-glutamate)
THF acts as a carrier of reactive single carbon units, which are bonded to N-5 and N-10.
Either serine or glycine can act as methylene donor, giving N5,N10-methyleneTHF. This behaves as "virtual formaldehyde" H2C=O in reactions.
The oxidation level can be changed to methyl or methenyl by reduction or oxidation; methenylTHF can be hydrolyzed to formylTHF.
These derivatives can be used in synthetic reactions as donors of single C at the appropriate oxidation level. This may be a more important role for glycine metabolism than potential delivery of single C to catabolic reactions.
Two genes (MAT1A and MAT2A) encode for the essential enzyme methionine adenosyltransferase (MAT), which catalyzes the biosynthesis of S-adenosylmethionine (SAMe) , the principal methyl donor and, in the liver, a precursor of glutathione.
- MAT1A is expressed mostly in the liver
- MAT2A is widely distributed. MAT2A is induced in the liver during periods of rapid growth and dedifferentiation. MAT2A activity
In human hepatocellular carcinoma (HCC) MAT1A is replaced by MAT2A. This is important pathogenetically because MAT2A expression is associated with lower SAMe levels and faster growth, whereas exogenous SAMe treatment inhibits growth.
Regulation by hypoxia of methionine adenosyltransferase activity and gene expression in rat hepatocytes. 1998
Oxygen supply to the hepatic parenchyma is compromised by long- or short-term ethanol consumption and pathological conditions such as cirrhosis. Impairment in the production of S-adenosyl-L-methionine, the major methylating agent, occurs during hypoxia. In this study, the molecular mechanisms implicated in the regulation of S-adenosyl-L-methionine synthesis by oxygen levels were investigated
Regulation by Diet
Methyl Cycle Genomics