Folate status and age affect the accumulation of L-isoaspartyl residues in rat liver proteins.
Formation of atypical L-isoaspartyl residues in proteins and peptides is a common, spontaneous and nonenzymatic modification of aspartyl and asparaginyl sites. The enzyme protein-L-isoaspartyl methyltransferase (PIMT) catalyzes the transfer of the methyl group of S-adenosyl-L-methionine (SAM) to these L-isoaspartyl sites, thereby allowing reisomerization and restoration of the original alpha peptide linkage. Because SAM is in part a product of folate metabolism, the present study was undertaken to determine the effects of folate deficiency on the presence of L-isoaspartyl residues in hepatic proteins. Young (weanling) and older (12 mo) Sprague-Dawley rats were fed a folate-sufficient (2 mg folate/kg diet) or folate-deficient (0 mg folate/kg diet) diet for 20 wk. Liver proteins were analyzed for L-isoaspartyl residues. This analysis was based on the PIMT-dependent incorporation of [(3)H]-methyl groups from [(3)H]-SAM and the subsequent (nonenzymatic) sublimation of these methyl groups into a nonaqueous scintillant. The amount of L-isoaspartyl residues in hepatic proteins was higher in younger folate-deficient than in folate-sufficient rats (deficient: 187 +/- 71, sufficient: 64 +/- 43 pmol/mg protein, P < 0.025). This difference, however, was not seen among the older groups of rats who instead exhibited a much larger accumulation of L-isoaspartyl residues in their hepatic proteins (deficient: 528 +/- 151, sufficient: 470 +/- 204 pmol/mg protein, P = 0.568). The importance of these observations is discussed.
Ghandour
Haifa
H
Vitamin Metabolism, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Lin
Bi-Fong
BF
Choi
Sang-Woon
SW
Mason
Joel B
JB
Selhub
Jacob
J
D000367:Age Factors; D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001224:Aspartic Acid; D005492:Folic Acid / Q000378:metabolism*; D005494:Folic Acid Deficiency / Q000378:metabolism*; D026581:Isoaspartic Acid / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008745:Methylation; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000378:metabolism
D026581:Isoaspartic Acid; D001224:Aspartic Acid; D012436:S-Adenosylmethionine; D005492:Folic Acid; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase