Developmental changes in the activity of phosphatidylethanolamine N-methyltransferases in rat brain.
The activity of phosphatidylethanolamine N-methyltransferase (PeMT), an enzymic system that catalyses the synthesis of phosphatidylcholine (PtdCho) via sequential methylation of phosphatidylethanolamine (PtdEtn) using S-adenosylmethionine (AdoMet) as a methyl donor, was examined in brain homogenates from rats of various ages. The data thus obtained were consistent with the existence of two distinct enzyme activities within this enzyme system, i.e. one catalysing the methylation of PtdEtn [to form phosphatidyl-N-monomethylethanolamine (PtdMeEtn)], and the other catalysing the methylations of PtdMeEtn and phosphatidyl-NN-dimethylethanolamine (PtdMe2Etn) (to form PtdMe2Etn and PtdCho, respectively). PeMT (PtdEtn-methylating) activity per g of brain was 4-fold higher in neonatal than in adult brains. The enzyme activity in adult brains exhibited Michaelis-Menten kinetics for AdoMet, and its affinity for AdoMet was high (apparent Km 1.6 microM). In neonatal brain the relationships between AdoMet concentrations and PtdMeEtn formation were more complex: a sigmoidal component (with a Hill coefficient of 2.7), requiring 90 microM-AdoMet for half-saturation predominated over the high-affinity component (similar to that of the adult brain). PeMT (PtdMe2Etn-methylating) activity per g of brain increased 2-fold between the 5th and the 20th postnatal days and remained constant thereafter; it was higher than that of PeMT (PtdEtn-methylating) activity at all ages studied, and its affinity for AdoMet was low (apparent Km 99 microM). No sexual dimorphism in brain PeMT activity was observed at any age. We conclude that PeMT (PtdEtn-methylating) catalyses the rate-limiting step in PtdCho synthesis in rat brain, and that PtdCho formation via this pathway may be greatest during the neonatal period.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001921:Brain / Q000201:enzymology* / Q000254:growth & development; D007700:Kinetics; D008780:Methyltransferases / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D050918:Phosphatidylethanolamine N-Methyltransferase; D010714:Phosphatidylethanolamines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C032000:phosphatidyl-N-monomethylaminoethanol; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase