Nutrition has had to come to terms with the domination of science by molecular biology. Can Nutrition find a place in the science of the post translational events by providing substrates for the modulation of these genetic metabolic programme?.
Hints are given by studies describing small molecular transfer reactions.
Acetylation as a regulatory post translational modifier. The general transcription factor TFIIB which is prerequisite for the initiation of polymerase II activity is acetylated. Acetyl CoA is involved in this reaction ( Choi et al Nature 2003, vol 424, pp 965-9 )
Methylation is involved in cancer linked epigenetic alteration , either through hypomethylation or hypermethylation . The breast cancer drug tamoxifen is a drug with distinct genomic activity and gene transcriptional regulation. ( Wu et al Nature 2005, vol 438, , pp 981- 987
Nicotinamide riboside increases the concentrations of nicotinamide adenine dinucleotide which activates the age related protein Sir2, well anyhow in yeast. Nature 2007, vol 447, p 118
Folic acid is a determinant of DNA methylation which is important in DNA activity. Ageing is associated with DNA hypomethylation. ( Choi et al 2005, British Journal of Nutrition vol 93,pp31-35)
The inhibition of histone deacetylases can improve memory capabilities in a genetically engineered mouse model of neurodegenera-tion in the central nervous system . Histone deacetylases remove acetyl groups from lysine amino acids in proteins, including the cell nucleus histones. Histones interact with DNA to form chromatin which control the accessibility of DNA for gene transcription. Acetylated histones form active chromatin complexes with DNA, which makes the DNA accessible to RNA polymerases, thereby regulating gene transcription
Inhibitors of Histone deacetylases block the ability of these enzymes to deacetylate histones, promoting histone acetylation in the nucleus and thus altering gene expression. Because altered transcription is known to be necessary for the formation of long-term memories, Histone deacetylases inhibitors have the potential to boost memory formation. This has been demonstrated in normal rats and mice
Sweatt Nature 2007, vol 447, pp151-152
Fischer et al Nature 2007, vol 447 pp 178-182.
There is much potential here for exciting studies.
- Martin Eastwood