PEMT
Phosphatidylethanolamine N-methyltransferase (EC 2.1.1.17) (EC 2.1.1.71) (PEAMT) (PEMT) (PEMT2) (Phospholipid methyltransferase) (PLMT) [PEMPT] [PNMT]
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Phosphatidylcholine (PC) is the predominant phospholipid component of circulating lipoproteins. The majority of PC is formed by the choline pathway. However, approximately one-third of hepatic PC can also be synthesized by phosphatidylethanolamine N-methyltransferase (PEMT). PEMT is required for normal secretion of very-low-density lipoproteins from the liver. We hypothesized that lack of PEMT would attenuate atherosclerosis and improve myocardial function. Investigate the contribution of PEMT to atherosclerotic lesion formation and cardiac function in mice that lack apolipoprotein E. Mice deficient in apolipoprotein E (Pemt( / )/Apoe(-/-)) and mice lacking both PEMT and apoE (Pemt(-/-)/Apoe(-/-)) were fed a chow diet for 1 year. The atherogenic lipoprotein profile of plasma of Apoe(-/-) mice was significantly improved by PEMT deficiency, with lower levels of triacylglycerol (45%) and cholesterol (≈25%) in the very-low-density lipoprotein and low-density/intermediate-density lipoprotein fractions, respectively (P < 0.05). Atherosclerotic lesion area was reduced by ≈30%, and aortic cholesteryl ester and cholesterol content were also reduced by ≈40% by PEMT deficiency (P < 0.05). By in vivo echocardiography, we detected a ≈50% improvement in systolic function in the Pemt(-/-)/Apoe(-/-) compared with Pemt( / )/Apoe(-/-) mice (P < 0.05). This was accompanied by a significant reduction in cardiac triacylglycerol (34%) in mice lacking PEMT. These results indicate that treatment strategies aimed at inhibition of PEMT might prevent the accumulation of cardiac triacylglycerol that predisposes individuals to compromised cardiac function.
MeSH Terms
- Aging
- Animals
- Aorta
- Apolipoproteins E
- Atherosclerosis
- Cholesterol
- Heart
- Heart Diseases
- Lipid Metabolism
- Lipoproteins
- Liver
- Mice
- Mice, Knockout
- Myocardium
- Phosphatidylcholines
- Phosphatidylethanolamine N-Methyltransferase
- Triglycerides
Morphological and biochemical changes take place in the membrane of aged brain. In particular, studies on aged rats report alterations in brain phospholipid synthesis and in phospholipid-specific fatty acid composition. However, no significant changes in main phospholipid class content have been reported in aged brain, possibly owing to alterations in the alternative pathways for phospholipid synthesis during aging. Therefore, the present study was designed to determine the effect of aging on the enzyme activities responsible for phospholipid synthesis by alternative pathways. Indifferent brain areas of adult (3.5-month-old) and aged (28.5-month-old) rats we examined: 1) the activity of base exchange enzymes, which is a calcium-dependent, energy-independent and calcium stimulated enzymatic pathway; 2) phosphatidylethanolamine (PE) synthesis by phosphatidylserine decarboxylase activity (PSD); 3) phosphatidylcholine (PC) synthesis by transfer of methyl groups to endogenous PE by phosphatidylethanolamine N-methyltransferase activity (PEMT); 4) the synthesis of phosphatidylglycerol (PG) through phospholipase D (PLD) activity. Because the dependence on and the stimulation by calcium of base-exchange reactions is a well known mechanism and alterations in calcium levels in rat brain have been reported, we decided to investigate PS synthesis in the presence of endogenous and exogenous calcium (2.5mM). PS synthesis increased in cerebral cortex (CC) and cerebellum (CRBL) of aged rats with respect to adult rats in basal conditions (without the addition of exogenous calcium), but more significant changes were observed in serine base exchange activity during aging when exogenous calcium was added. PEMT activity in aged CC increased by 100%, the principal modification being observed in the first methylated product of the sequential reaction. Furthermore, the transphosphatidyl reaction was higher in aged brain as indicated by the increased PG synthesis. Our findings allow us to conclude that age affects some alternative pathways for phospholipid synthesis in the central nervous system, and indicate the presence of a compensatory mechanism to provide a pool of phospholipid classes for the maintenance of cellular membrane lipid composition during aging.
MeSH Terms
- Aging
- Animals
- Brain
- Cerebellum
- Cerebral Cortex
- Male
- Methyltransferases
- Phosphatidylethanolamine N-Methyltransferase
- Phospholipase D
- Phospholipids
- Rats
- Rats, Wistar
- Serine