Hepatic Phosphatidylethanolamine N-Methyltransferase, Unexpected Roles in Animal Biochemistry and Physiology

In 1961, when Bremer and Greenberg (1Bremer J. Greenberg D.M. Biochim. Biophys. Acta. 1961; 46: 205-216Crossref Scopus (357) Google Scholar) characterized the methylation reactions that convert phosphatidylethanolamine (PE) 4The abbreviations used are: PE, phosphatidylethanolamine; PC, phosphatidylcholine; PEMT, phosphatidylethanolamine N-methyltransferase; ER, endoplasmic reticulum; AdoMet, S-adenosylmethionine; CT, CTP:phosphocholine cytidylyltransferase; CD, choline-deficient; TG, triacyglycerol(s); VLDL, very low density lipoprotein; HDL, high density lipoprotein; AdoHcy, S-adenosylhomocysteine; Hcy, homocysteine. 4The abbreviations used are: PE, phosphatidylethanolamine; PC, phosphatidylcholine; PEMT, phosphatidylethanolamine N-methyltransferase; ER, endoplasmic reticulum; AdoMet, S-adenosylmethionine; CT, CTP:phosphocholine cytidylyltransferase; CD, choline-deficient; TG, triacyglycerol(s); VLDL, very low density lipoprotein; HDL, high density lipoprotein; AdoHcy, S-adenosylhomocysteine; Hcy, homocysteine. to phosphatidylcholine (PC), it is unlikely that they would have predicted the physiological impact of this biosynthetic conversion. Similarly, when Ridgway and Vance (2Ridgway N.D. Vance D.E. J. Biol. Chem. 1987; 262: 17231-17239Abstract Full Text PDF PubMed Google Scholar) succeeded in purification of the hepatic enzyme PE N-methyltransferase (PEMT), we considered this enzyme to be important only for making PC in the liver. Subsequent research has now clearly shown that PEMT has critical roles that are additional to the important role of supplying PC for the liver. This review will summarize research on PEMT and its impact on animal biochemistry and physiology.Biochemical Characterization of PEMTPEMT is localized to the endoplasmic reticulum (ER) and the mitochondrial associated membranes (a subfraction of the ER) of the liver (3Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar, 4Cui Z. Vance J.E. Chen M.H. Voelker D.R. Vance D.E. J. Biol. Chem. 1993; 268: 16655-16663Abstract Full Text PDF PubMed Google Scholar). PEMT spans the membrane with four transmembrane sequences (5Shields D.J. Lehner R. Agellon L.B. Vance D.E. J. Biol. Chem. 2003; 278: 2956-2962Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar). PEMT catalyzes all three methylation reactions in the conversion of PE to PC (Fig. 1). The methyl donor is S-adenosylmethionine (AdoMet). The binding site on PEMT for AdoMet has been localized to the cytosolic surface of the ER (6Shields D.J. Altarejos J.Y. Wang X. Agellon L.B. Vance D.E. J. Biol. Chem. 2003; 278: 35826-35836Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar). Residues critical for binding of PE to PEMT have not been identified.PEMT and Its Evolutionary SignificancePEMT is essentially a hepatocyte-specific enzyme (7Vance D.E. Ridgway N.D. Prog. Lipid Res. 1988; 27: 61-79Crossref PubMed Scopus (194) Google Scholar). Also present in the liver is the CDP-choline pathway for PC biosynthesis (Fig. 2) first described by Kennedy and Weiss (8Kennedy E.P. Weiss S.B. J. Biol. Chem. 1956; 222: 193-214Abstract Full Text PDF PubMed Google Scholar, 9Kennedy E.P. Annu. Rev. Biochem. 1957; 26: 119-148Crossref PubMed Scopus (152) Google Scholar). This pathway is essential because cells that lack the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CT) do not survive (10Esko J.D. Nishijima M. Raetz C.R.H. Proc. Natl. Acad. Sci. U. S. A. 1982; 79: 1698-1702Crossref PubMed Scopus (58) Google Scholar) and undergo apoptosis Z. M. Chen M.H. M. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Similarly, with that S. S. Biol. PubMed Scopus Google Scholar). the M. S. Biochim. Biophys. Acta. 2003; PubMed Scopus Google Scholar). of the of this that is not in S. J.E. Wang J. Biol. PubMed Scopus Google Scholar). for of the in the liver Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the liver has PC biosynthetic the CDP-choline PEMT survive in In the the and to this to that CDP-choline pathway for PC is by that the and is by that the and PEMT is localized to and spans with and Z. Agellon L.B. Vance D.E. J. Lipid Res. Full Text PDF PubMed Google Scholar). and PEMT R. Agellon L.B. Vance D.E. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). PEMT in the the of hepatic PC and PE and in it that PEMT This not because the CDP-choline pathway in the of PC biosynthesis the CDP-choline we the a the liver Agellon L.B. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The of PC in the liver by with that in and the of and by that PEMT has in to PC PC when is in the M.H. Z. J. Google and a for the of a in and the been used to of and A. Res. PubMed Scopus Google Scholar). The of and is that has critical roles in PC biosynthesis and the of for the additional reactions J.E. M. S. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). The of PEMT would only the conversion of PE to in hepatic PC in M.H. Z. J. Google Scholar) to this The liver and that of The PC that is the liver is for a Biochem. PubMed Scopus Google Scholar). The of PC in the liver would be the liver the the of its of PC is in the the in hepatic PC is not PC biosynthesis is for very low density Z. Vance D.E. J. Biol. Chem. 1988; Full Text PDF PubMed Google Scholar). In to the of PC to we the of the of a of the in PC with in PC Vance D.E. J. Lipid Res. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). of PC for is and R. 1993; Full Text PDF PubMed Scopus Google Scholar) the of the a for of PC we the with the and a that the the they liver the and for Z. Agellon L.B. Vance D.E. J. Biol. Chem. 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This and when with the of with PEMT in the pathway with on PEMT have been shown to be on Chen Vance D.E. PubMed Scopus Google Scholar). The of PEMT to be because of by PEMT Vance D.E. J. PubMed Scopus Google Scholar). of with the in PEMT be a PEMT and this we the of to and and PEMT and biosynthesis is for of the of Z. Vance D.E. J. Biol. Chem. 1988; Full Text PDF PubMed Google Scholar) by of and the be by Z. Vance D.E. J. Biol. Chem. Full Text PDF PubMed Google Scholar). only not is the is not A. Vance D.E. Vance J.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The for the of in is by the of Vance D.E. Biochim. Biophys. Acta. PubMed Scopus Google Scholar) Z. Vance D.E. Biochim. Biophys. Acta. PubMed Scopus Google Scholar) to for in the of the of the role of PEMT in the of of by in with Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In a of of not in a for PEMT cells lack a of Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). in that not of TG, and in Vance D.E. J. Biol. Chem. 2003; 278: Full Text Full Text PDF PubMed Scopus (152) Google Scholar). of of in the of a with The for this is not Vance D.E. J. Lipid Res. 2003; Full Text Full Text PDF PubMed Scopus Google the PEMT pathway is in for we the pathway for PC biosynthesis is that in liver Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). with of TG, PC, and and a of of in the of PEMT that not for the of Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). for PC biosynthesis are for the of in the of PEMT we be do not we the with that the low density and the a high for a in in the density with the density and in is high density The of and PC of in of Vance D.E. J. Biol. Chem. 2003; 278: Full Text Full Text PDF PubMed Scopus (152) Google Scholar). Similarly, the of by in the Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). for PEMT in a in is that of to this not in and of a for HDL, and this the of the of and to have important role in hepatic PC are a of liver do not Z. Agellon L.B. Vance D.E. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). of liver is in and for the is that in the is in the first of and of the PC is to the liver Z. Agellon L.B. Vance D.E. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). is in in is to the it be and the to it that PC to the liver and in hepatic PC and of the PEMT reactions is (Fig. 1). is to and by the of is for the of and J. PubMed Scopus Google Scholar) and PubMed Scopus Google Scholar). has been with of S. A. J. J. PubMed Scopus Google J. J. J. PubMed Scopus Google and J. J. PubMed Scopus Google is that methylation and are are J.E. M. S. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). This be because a has shown that of in and animal J.E. M. S. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). PEMT for the of PC in the liver and are for PC we that PEMT to of PEMT by Vance D.E. J. Biol. Chem. 2003; 278: Full Text Full Text PDF PubMed Scopus Google Scholar). the PEMT not the of in and because the of hepatic AdoMet and we that PEMT Vance D.E. J. Biol. Chem. 2003; 278: Full Text Full Text PDF PubMed Scopus Google cells have PEMT of PEMT in cells the with cells Vance D.E. J. Biol. Chem. 2003; 278: Full Text Full Text PDF PubMed Scopus Google Scholar). of in the ER of PEMT in of PEMT the ER to the This of PEMT not D.J. S. Agellon L.B. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). to the of PEMT of the PEMT Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In with PE methylation in Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the in hepatic and in the and in Vance D.E. J. Biol. Chem. 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Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). to PC the PEMT of is the for AdoMet PEMT is a in AdoMet and in to its role in PC biosynthesis and and PEMT first characterized in Z. Agellon L.B. Vance D.E. J. Lipid Res. Full Text PDF PubMed Google Scholar). the first on of and M. J. J. PubMed Scopus Google Scholar) of PEMT by of with for in and PEMT in a the first to are are in the PEMT is associated with liver J. M. Wang S. J. PubMed Scopus Google Scholar). and with liver for a of the PEMT in of the with liver and in of Wang J. A. M. M. S. S. J. 46: Full Text Full Text PDF PubMed Scopus Google Scholar) a of the and liver In the and in the S. J. PubMed Scopus Google Scholar). The in the J. Scopus Google in the by J. M. Wang S. J. PubMed Scopus Google only a the and liver J. Scopus Google Scholar). not all of the the not to liver. the to liver when is J. Scopus Google the PEMT in J. M. Wang S. J. PubMed Scopus Google Scholar). not to PEMT in the not the of PEMT the of the PEMT has not been clearly in now that PEMT has important roles that PC in the liver. PEMT has a role in a of PC to PE in the liver when the of is PEMT to and PEMT has a role in that be by the PEMT has important in the of The role of PEMT in and is In 1961, when Bremer and Greenberg (1Bremer J. Greenberg D.M. Biochim. Biophys. Acta. 1961; 46: 205-216Crossref Scopus (357) Google Scholar) characterized the methylation reactions that convert phosphatidylethanolamine (PE) 4The abbreviations used are: PE, phosphatidylethanolamine; PC, phosphatidylcholine; PEMT, phosphatidylethanolamine N-methyltransferase; ER, endoplasmic reticulum; AdoMet, S-adenosylmethionine; CT, CTP:phosphocholine cytidylyltransferase; CD, choline-deficient; TG, triacyglycerol(s); VLDL, very low density lipoprotein; HDL, high density lipoprotein; AdoHcy, S-adenosylhomocysteine; Hcy, homocysteine. 4The abbreviations used are: PE, phosphatidylethanolamine; PC, phosphatidylcholine; PEMT, phosphatidylethanolamine N-methyltransferase; ER, endoplasmic reticulum; AdoMet, S-adenosylmethionine; CT, CTP:phosphocholine cytidylyltransferase; CD, choline-deficient; TG, triacyglycerol(s); VLDL, very low density lipoprotein; HDL, high density lipoprotein; AdoHcy, S-adenosylhomocysteine; Hcy, homocysteine. to phosphatidylcholine (PC), it is unlikely that they would have predicted the physiological impact of this biosynthetic conversion. Similarly, when Ridgway and Vance (2Ridgway N.D. Vance D.E. J. Biol. Chem. 1987; 262: 17231-17239Abstract Full Text PDF PubMed Google Scholar) succeeded in purification of the hepatic enzyme PE N-methyltransferase (PEMT), we considered this enzyme to be important only for making PC in the liver. Subsequent research has now clearly shown that PEMT has critical roles that are additional to the important role of supplying PC for the liver. This review will summarize research on PEMT and its impact on animal biochemistry and Characterization of PEMTPEMT is localized to the endoplasmic reticulum (ER) and the mitochondrial associated membranes (a subfraction of the ER) of the liver (3Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar, 4Cui Z. Vance J.E. Chen M.H. Voelker D.R. Vance D.E. J. Biol. Chem. 1993; 268: 16655-16663Abstract Full Text PDF PubMed Google Scholar). PEMT spans the membrane with four transmembrane sequences (5Shields D.J. Lehner R. Agellon L.B. Vance D.E. J. Biol. Chem. 2003; 278: 2956-2962Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar). PEMT catalyzes all three methylation reactions in the conversion of PE to PC (Fig. 1). The methyl donor is S-adenosylmethionine (AdoMet). The binding site on PEMT for AdoMet has been localized to the cytosolic surface of the ER (6Shields D.J. Altarejos J.Y. Wang X. Agellon L.B. Vance D.E. J. Biol. Chem. 2003; 278: 35826-35836Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar). Residues critical for binding of PE to PEMT have not been PEMT is localized to the endoplasmic reticulum (ER) and the mitochondrial associated membranes (a subfraction of the ER) of the liver (3Vance J.E. J. Biol. Chem. 1990; 265: 7248-7256Abstract Full Text PDF PubMed Google Scholar, 4Cui Z. Vance J.E. Chen M.H. Voelker D.R. Vance D.E. J. Biol. Chem. 1993; 268: 16655-16663Abstract Full Text PDF PubMed Google Scholar). PEMT spans the membrane with four transmembrane sequences (5Shields D.J. Lehner R. Agellon L.B. Vance D.E. J. Biol. Chem. 2003; 278: 2956-2962Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar). PEMT catalyzes all three methylation reactions in the conversion of PE to PC (Fig. 1). The methyl donor is S-adenosylmethionine (AdoMet). The binding site on PEMT for AdoMet has been localized to the cytosolic surface of the ER (6Shields D.J. Altarejos J.Y. Wang X. Agellon L.B. Vance D.E. J. Biol. Chem. 2003; 278: 35826-35836Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar). Residues critical for binding of PE to PEMT have not been PEMT and Its Evolutionary SignificancePEMT is essentially a hepatocyte-specific enzyme (7Vance D.E. Ridgway N.D. Prog. Lipid Res. 1988; 27: 61-79Crossref PubMed Scopus (194) Google Scholar). Also present in the liver is the CDP-choline pathway for PC biosynthesis (Fig. 2) first described by Kennedy and Weiss (8Kennedy E.P. Weiss S.B. J. Biol. Chem. 1956; 222: 193-214Abstract Full Text PDF PubMed Google Scholar, 9Kennedy E.P. Annu. Rev. Biochem. 1957; 26: 119-148Crossref PubMed Scopus (152) Google Scholar). This pathway is essential because cells that lack the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CT) do not survive (10Esko J.D. Nishijima M. Raetz C.R.H. Proc. Natl. Acad. Sci. U. S. A. 1982; 79: 1698-1702Crossref PubMed Scopus (58) Google Scholar) and undergo apoptosis Z. M. Chen M.H. M. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Similarly, with that S. S. Biol. PubMed Scopus Google Scholar). the M. S. Biochim. Biophys. Acta. 2003; PubMed Scopus Google Scholar). of the of this that is not in S. J.E. Wang J. Biol. PubMed Scopus Google Scholar). for of the in the liver Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the liver has PC biosynthetic the CDP-choline PEMT survive in In the the and to this to that PEMT is localized to and spans with and Z. Agellon L.B. Vance D.E. J. Lipid Res. Full Text PDF PubMed Google Scholar). and PEMT R. Agellon L.B. Vance D.E. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). PEMT in the the of hepatic PC and PE and in it that PEMT This not because the CDP-choline pathway in the of PC biosynthesis the CDP-choline we the a the liver Agellon L.B. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The of PC in the liver by with that in and the of and by that PEMT has in to PC PC when is in the M.H. Z. J. Google Scholar). PEMT is essentially a hepatocyte-specific enzyme (7Vance D.E. Ridgway N.D. Prog. Lipid Res. 1988; 27: 61-79Crossref PubMed Scopus (194) Google Scholar). Also present in the liver is the CDP-choline pathway for PC biosynthesis (Fig. 2) first described by Kennedy and Weiss (8Kennedy E.P. Weiss S.B. J. Biol. Chem. 1956; 222: 193-214Abstract Full Text PDF PubMed Google Scholar, 9Kennedy E.P. Annu. Rev. Biochem. 1957; 26: 119-148Crossref PubMed Scopus (152) Google Scholar). This pathway is essential because cells that lack the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CT) do not survive (10Esko J.D. Nishijima M. Raetz C.R.H. Proc. Natl. Acad. Sci. U. S. A. 1982; 79: 1698-1702Crossref PubMed Scopus (58) Google Scholar) and undergo apoptosis Z. M. Chen M.H. M. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Similarly, with that S. S. Biol. PubMed Scopus Google Scholar). the M. S. Biochim. Biophys. Acta. 2003; PubMed Scopus Google Scholar). of the of this that is not in S. J.E. Wang J. Biol. PubMed Scopus Google Scholar). for of the in the liver Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the liver has PC biosynthetic the CDP-choline PEMT survive in In the the and to this to that The PEMT is localized to and spans with and Z. Agellon L.B. Vance D.E. J. Lipid Res. Full Text PDF PubMed Google Scholar). and PEMT R. Agellon L.B. Vance D.E. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). PEMT in the the of hepatic PC and PE and in it that PEMT This not because the CDP-choline pathway in the of PC biosynthesis the CDP-choline we the a the liver Agellon L.B. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The of PC in the liver by with that in and the of and by that PEMT has in to PC PC when is in the M.H. Z. J. Google Scholar). PEMT, and a for the of a in and the been used to of and A. Res. PubMed Scopus Google Scholar). The of and is that has critical roles in PC biosynthesis and the of for the additional reactions J.E. M. S. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). The of PEMT would only the conversion of PE to in hepatic PC in M.H. Z. J. Google Scholar) to this The liver and that of The PC that is the liver is for a Biochem. PubMed Scopus Google Scholar). The of PC in the liver would be the liver the the of its of PC is in the the in hepatic PC is not PC biosynthesis is for very low density Z. Vance D.E. J. Biol. Chem. 1988; Full Text PDF PubMed Google Scholar). In to the of PC to we the of the of a of the in PC with in PC Vance D.E. J. Lipid Res. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). of PC for is and R. 1993; Full Text PDF PubMed Scopus Google Scholar) the of the a for of PC we the with the and a that the the they liver the and for Z. Agellon L.B. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). by the the PC in the of by with and the the liver in not to this in PC, PC in of the that that the of hepatic PE not in the the the of PE in the of Z. Agellon L.B. M. A. Vance D.E. Full Text Full Text PDF PubMed Scopus Google Scholar). the of PC to PE to in the of with in the of a the and the of (a hepatic enzyme that membrane when in The in of membranes the of Z. Agellon L.B. M. A. Vance D.E. Full Text Full Text PDF PubMed Scopus Google Scholar). The of and not in the of and is a PE has M. Vance D.E. Vance J.E. of and Scholar). that the of PC, not PE, in the of of the PE the PC on the surface Z. Agellon L.B. M. A. Vance D.E. Full Text Full Text PDF PubMed Scopus Google Scholar). This the of the in the membrane that would in this we used a that PE M. Res. PubMed Scopus Google Scholar). the for with the by cells (Fig. Z. Agellon L.B. M. A. Vance D.E. Full Text Full Text PDF PubMed Scopus Google Scholar). the that PE on the surface of with in the this Z. Agellon L.B. M. A. Vance D.E. Full Text Full Text PDF PubMed Scopus Google Scholar). the that a of PC to PE in hepatic membranes to membrane and additional that a in membrane we used cytidylyltransferase to the biosynthesis of PE in Z. Agellon L.B. M. A. Vance D.E. Full Text Full Text PDF PubMed Scopus Google Scholar). the PE and the in with of the Z. Agellon L.B. M. A. Vance D.E. Full Text Full Text PDF PubMed Scopus Google Scholar). Similarly, when the the of the and a in for the that because of of the membrane that to a of PC to on the of in have shown that with this have a in the in hepatic Z. Agellon L.B. M. A. Vance D.E. Full Text Full Text PDF PubMed Scopus Google PEMT and hepatic has been in a of with biosynthesis of PC Vance D.E. PubMed Scopus Google Scholar). This and when with the of with PEMT in the pathway with on PEMT have been shown to be on Chen Vance D.E. 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Full Text Full Text PDF PubMed Scopus Google Scholar). This the of the in the membrane that would in this we used a that PE M. Res. PubMed Scopus Google Scholar). the for with the by cells (Fig. Z. Agellon L.B. M. A. Vance D.E. Full Text Full Text PDF PubMed Scopus Google Scholar). the that PE on the surface of with in the this Z. Agellon L.B. M. A. Vance D.E. Full Text Full Text PDF PubMed Scopus Google Scholar). the that a of PC to PE in hepatic membranes to membrane and additional that a in membrane we used cytidylyltransferase to the biosynthesis of PE in Z. Agellon L.B. M. A. Vance D.E. Full Text Full Text PDF PubMed Scopus Google Scholar). the PE and the in with of the Z. Agellon L.B. M. A. Vance D.E. Full Text Full Text PDF PubMed Scopus Google Scholar). Similarly, when the the of the and a in The for the that because of of the membrane that to a of PC to on the of in have shown that with this have a in the in hepatic Z. Agellon L.B. M. A. Vance D.E. 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