Isoaspartic acid residue

FIGURE 3 Deamidation of asparagine by succinimide formation. L-aspartic acid and L-isoaspartic acid residues are the products of L-asparagine degradation via a succinimide intermediate. Aspartic acid residues can also form the succinimide intermediate by a similar mechanism with a loss of water. Figure based on that of Clarice et al. ... 

Elevated levels of isoaspartate residues have been noted within aged proteins. A extracted from parenchyma contains predominantly isoaspartate residues at positions 1 and 7. The aspartic acid residue at position 23 seems largely unaffected, perhaps because of steric protection by the neighbouring valine. It was found that synthetic A with these substitutions resulted in more stable -sheets. These two alterations are found near the beginning and... 

Whether there is any other connection between anticonvulsant activity and camosine s antiaging actions is obviously highly speculative. It may be relevant to note that epileptic seizures and a shortened life span, together with altered protein accumulation, are consequences of PIMT-deficiency in mice, while treatment with valproic acid, an anticonvulsant, partially suppresses these symptoms including effects on life span (Yamamoto et ah, 1998). Conversely, PIMT overexpression can increase life span of Drosophila (Bennet et ah, 2003). Furthermore, the chemistry of some anticonvulsants (ethosuximide) resembles quite closely the structure of the succinimide intermediate formed during both asparagine deamidation and PIMT-mediated repair of isoaspartate residues. One conjectures whether there are any relationships between these... 

The biological role of PIMT involves the selective methylation of isoaspartate residues followed by a demethylation step to reform the succi-nimide intermediate. The demethylation causes the release of methanol which can be converted to formaldehyde and finally to formic acid, as demonstrated in rat brain preparations. It was found that S-adenosyl-methionine (SAM), the methyl donor, caused formaldehyde levels to rise in the rat brain homogenates, thus suggesting that excessive formaldehyde may be a precipitating factor in Parkinsons s disease (PD) (Lee et ah, 2008). It is possible that carnosine could suppress formaldehyde toxicity by reacting with it to generate a carnosine-formaldehyde adduct. This should be a relatively easy experiment to perform to test this prediction. 

---