Biomedical Research Education & Training
Faculty Member

Wagner, Conrad, Ph. D.
Professor Emeritus, Biochemistry

Lab Url: N/A

Phone Number: (615) 343 9866; Pager: 615-201-1731

Email Address:

Wagner, Conrad's picture
Academic history
B.A., City College of NY
M.S., Michigan
Ph.D., Michigan
, Naval Medical Research Institute
, N.I.H.

Office Address   Mailing Address

620 Light Hall

620 Light Hall 0146

Research Keywords
Vitamin metabolism, amino acid metabolism, one-carbon metabolism, folic acid, vitamin B12, enzyme mechanisms,Cancer

Research Specialty
Research Specialty: Metabolism of one-carbon compounds

Research Description
Research Description: Our laboratory has been involved with various aspects of one-carbon metabolism for many years. These include the roles of the coenzyme forms of the vitamin, folic acid, and the enzymes that carry out these functions. Our approach has been to investigate every available aspect of Biochemistry to accomplish this including enzymology, mass spectrometry, crystallography, molecular biology and nutritional manipulation.

Our latest work has focused on developing a mouse knock-out of the enzyme GNMT which is responsible for the regulation of levels of S-adenosymethionine (SAM). This GNMT knockout mouse spontaneously develops fatty liver and hepatocellular carcinoma that is a result of methylation of tumor suppressors in the promoter region of the gene. SAM, a metabolic product of methionine metabolism, is the major donor of methyl groups in the body. This line of investigation has led us to the discovery of two new metabolic diseases. We have recently shown that the histone demethylase, LSD1, is a folate binding protein in which the folate probably serves to scavenge the formaldehyde that is a product of the demethylase reaction. This finding suggests that the levels of folate in the diet can play a role in gene expression. More recently we have shown that products of methionine breakdown in serum may serve as markers for the risk of developing metastasis of prostate cancer.

Luka, Z, Moss, F, Loukachevitch, LV, Bornhop, DJ, Wagner, C. Histone demethylase LSD1 is a folate-binding protein. Biochemistry, 50(21), 4750-6, 2011

Wagner, C, Fredi, J, Bick, J, McPherson, J. Monitoring myocardial recovery during induced hypothermia with a disposable monoplane TEE probe. Resuscitation, 82(3), 355-7, 2011

Wagner, CE, Bick, JS, Webster, BH, Selby, JH, Byrne, JG. Use of a Miniaturized Transesophageal Echocardiographic Probe in the Intensive Care Unit for Diagnosis and Treatment of a Hemodynamically Unstable Patient After Aortic Valve Replacement. J Cardiothorac Vasc Anesth, 2011

Luka, Z, Mudd, SH, Wagner, C. Glycine N-methyltransferase and regulation of S-adenosylmethionine levels. J Biol Chem, 284(34), 22507-11, 2009 PMCID:2755656

Shrubsole, MJ, Yang, G, Gao, YT, Chow, WH, Shu, XO, Cai, Q, Rothman, N, Gao, J, Wagner, C, Zheng, W. Dietary B vitamin and methionine intakes and plasma folate are not associated with colorectal cancer risk in Chinese women. Cancer Epidemiol Biomarkers Prev, 18(3), 1003-6, 2009 PMCID:2677023

Luka, Z, Loukachevitch, LV, Wagner, C. Acetylation of N-terminal valine of glycine N-methyltransferase affects enzyme inhibition by folate. Biochim Biophys Acta, 1784(9), 1342-6, 2008 PMCID:2576408

Capdevila, A, Burk, RF, Freedman, J, Frantzen, F, Alfheim, I, Wagner, C. A simple rapid immunoassay for S-adenosylhomocysteine in plasma. J Nutr Biochem, 18(12), 827-31, 2007 PMCID:2196216

Luka, Z, Pakhomova, S, Loukachevitch, LV, Egli, M, Newcomer, ME, Wagner, C. 5-methyltetrahydrofolate is bound in intersubunit areas of rat liver folate-binding protein glycine N-methyltransferase. J Biol Chem, 282(6), 4069-75, 2007 PMCID:2196216

Luka, Z, Pakhomova, S, Luka, Y, Newcomer, ME, Wagner, C. Destabilization of human glycine N-methyltransferase by H176N mutation. Protein Sci, 16(9), 1957-64, 2007 PMCID:2206963

Wagner, C, Koury, MJ. S-Adenosylhomocysteine: a better indicator of vascular disease than homocysteine. Am J Clin Nutr, 86(6), 1581-5, 2007 PMCID:2576408

Jabs, K, Koury, MJ, Dupont, WD, Wagner, C. Relationship between plasma S-adenosylhomocysteine concentration and glomerular filtration rate in children. Metabolism, 55(2), 252-7, 2006

Luka, Z, Capdevila, A, Mato, JM, Wagner, C. A glycine N-methyltransferase knockout mouse model for humans with deficiency of this enzyme. Transgenic Res, 15(3), 393-7, 2006 PMCID:2792375

Luka, Z, Ham, AJ, Norris, JL, Yeo, EJ, Yermalitsky, V, Glenn, B, Caprioli, RM, Liebler, DC, Wagner, C. Identification of phosphorylation sites in glycine N-methyltransferase from rat liver. Protein Sci, 15(4), 785-94, 2006 PMCID:2242492

Luka, Z, Wagner, C. Human glycine N-methyltransferase is unfolded by urea through a compact monomer state. Arch Biochem Biophys, 420(1), 153-60, 2003

Luka, Z, Wagner, C. Effect of naturally occurring mutations in human glycine N-methyltransferase on activity and conformation. Biochem Biophys Res Commun, 312(4), 1067-72, 2003

Luka, Z, Wagner, C. Expression and purification of glycine N-methyltransferases in Escherichia coli. Protein Expr Purif, 28(2), 280-6, 2003

Luka, Z, Cerone, R, Phillips, JA, Mudd, HS, Wagner, C. Mutations in human glycine N-methyltransferase give insights into its role in methionine metabolism. Hum Genet, 110(1), 68-74, 2002

Kerins, DM, Koury, MJ, Capdevila, A, Rana, S, Wagner, C. Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine. Am J Clin Nutr, 74(6), 723-9, 2001

Krupenko, SA, Wagner, C. Aspartate 142 is involved in both hydrolase and dehydrogenase catalytic centers of 10-formyltetrahydrofolate dehydrogenase. J Biol Chem, 274(50), 35777-84, 1999

Yeo, EJ, Briggs, WT, Wagner, C. Inhibition of glycine N-methyltransferase by 5-methyltetrahydrofolate pentaglutamate. J Biol Chem, 274(53), 37559-64, 1999

Capdevila, A, Wagner, C. Measurement of plasma S-adenosylmethionine and S-adenosylhomocysteine as their fluorescent isoindoles. Anal Biochem, 264(2), 180-4, 1998

Krupenko, SA, Wagner, C. Overexpression of functional hydrolase domain of rat liver 10-formyltetrahydrofolate dehydrogenase in Escherichia coli. Protein Expr Purif, 14(1), 146-52, 1998

Krupenko,S. and Wagner,C. "Overexpression of Functional Hydrolase Domain of 10-Formyltetrahydrofolate Dehydrogenase in E coli". Protein Expression and Purification(14), 145-152, 1998

Pattanayek, R, Newcomer, ME, Wagner, C. Crystal structure of apo-glycine N-methyltransferase (GNMT). Protein Sci, 7(6), 1326-31, 1998 PMCID:2144038

Pattanayek,R., Wagner,C. and Newcomer,M.E. "Crystal Structure of Apo- Glycine N-methyltransferase". Protein Science, 7, 1326-1331, 1998

Capdevila, A, Decha-Umphai, W, Song, KH, Borchardt, RT, Wagner, C. Pancreatic exocrine secretion is blocked by inhibitors of methylation. Arch Biochem Biophys, 345(1), 47-55, 1997

Capdevila,A., Decha-Umphai,W., Song, K.-H., Borchardt,R.T. and Wagner,C. "Pancreatic Exocrine Secretion is Blocked by Inhibitors of Methylation". Arch. Biochem. Biophys, 345, 47-55, 1997

Horne,D.W., Holloway,R.S. and Wagner,C. "Transport of S- adenosylmethionine in Isolated Rat Liver Mitochondria." . Arch. Biochem. Biophys., 343, 201-206, 1997

Krupenko, NI, Wagner, C. Transport of rat liver glycine N-methyltransferase into rat liver nuclei. J Biol Chem, 272(43), 27140-6, 1997

Krupenko, SA, Wagner, C, Cook, RJ. Domain structure of rat 10-formyltetrahydrofolate dehydrogenase. Resolution of the amino-terminal domain as 10-formyltetrahydrofolate hydrolase. J Biol Chem, 272(15), 10273-8, 1997

Krupenko, SA, Wagner, C, Cook, RJ. Expression, purification, and properties of the aldehyde dehydrogenase homologous carboxyl-terminal domain of rat 10-formyltetrahydrofolate dehydrogenase. J Biol Chem, 272(15), 10266-72, 1997

Krupenko,N. and Wagner,C. "Transport of Rat Liver Glycine N- methyltransferase Into Rat Liver Nuclei" . J. Biol. Chem., 272, 27140-27146, 1997

Krupenko,S.A., Wagner,C. and Cook,R.J. "Expression, Purification and Properties of the Aldehyde Dehydrogenase Homologous Carboxyl-terminal Domain of Rat 10- formyltetrahydrofolate Dehydrogenase". J. Biol. Chem., 272, 10266-10272, 1997

Krupenko,S.A., Wagner,C. and Cook,R.J. "Domain Structure of Rat 10- formyltetrahydrofolate Dehydrogenase: Resolution of the Amino-terminal Domain as 10- formyltetrahydrofolate Hydrolase.". J. Biol. Chem., 272, 10273-, 1997

Wagner, C. Symposium on the subcellular compartmentation of folate metabolism. J Nutr, 126(4 Suppl), 1228S-34S, 1996

Cook, RJ, Wagner, C. Enzymatic activities of rat liver cytosol 10-formyltetrahydrofolate dehydrogenase. Arch Biochem Biophys, 321(2), 336-44, 1995

Krupenko, SA, Horstman, DA, Wagner, C, Cook, RJ. Baculovirus expression and purification of rat 10-formyltetrahydrofolate dehydrogenase. Protein Expr Purif, 6(4), 457-64, 1995

Krupenko, SA, Wagner, C, Cook, RJ. Recombinant 10-formyltetrahydrofolate dehydrogenase catalyses both dehydrogenase and hydrolase reactions utilizing the synthetic substrate 10-formyl-5,8-dideazafolate. Biochem J, 306 ( Pt 3), 651-5, 1995 PMCID:1136571

Krupenko, SA, Wagner, C, Cook, RJ. Cysteine 707 is involved in the dehydrogenase activity site of rat 10-formyltetrahydrofolate dehydrogenase. J Biol Chem, 270(2), 519-22, 1995

Wagner, C, Briggs, WT, Horne, DW, Cook, RJ. 10-Formyltetrahydrofolate dehydrogenase: identification of the natural folate ligand, covalent labeling, and partial tryptic digestion. Arch Biochem Biophys, 316(1), 141-7, 1995

Yeo, EJ, Wagner, C. Tissue distribution of glycine N-methyltransferase, a major folate-binding protein of liver. Proc Natl Acad Sci U S A, 91(1), 210-4, 1994 PMCID:42916

Balaghi, M, Horne, DW, Wagner, C. Hepatic one-carbon metabolism in early folate deficiency in rats. Biochem J, 291 ( Pt 1), 145-9, 1993 PMCID:1132493

Balaghi, M, Horne, DW, Woodward, SC, Wagner, C. Pancreatic one-carbon metabolism in early folate deficiency in rats. Am J Clin Nutr, 58(2), 198-203, 1993

Balaghi, M, Wagner, C. DNA methylation in folate deficiency: use of CpG methylase. Biochem Biophys Res Commun, 193(3), 1184-90, 1993

Balaghi, M, Wagner, C. Methyl group metabolism in the pancreas of folate-deficient rats. J Nutr, 122(7), 1391-6, 1992

Yeo, EJ, Wagner, C. Purification and properties of pancreatic glycine N-methyltransferase. J Biol Chem, 267(34), 24669-74, 1992

Cook, RJ, Lloyd, RS, Wagner, C. Isolation and characterization of cDNA clones for rat liver 10-formyltetrahydrofolate dehydrogenase. J Biol Chem, 266(8), 4965-73, 1991

Wickwire, BM, Wagner, C, Broquist, HP. Pipecolic acid biosynthesis in Rhizoctonia leguminicola. II. Saccharopine oxidase: a unique flavin enzyme involved in pipecolic acid biosynthesis. J Biol Chem, 265(25), 14748-53, 1990

Cook, RJ, Horne, DW, Wagner, C. Effect of dietary methyl group deficiency on one-carbon metabolism in rats. J Nutr, 119(4), 612-7, 1989

Horne, DW, Cook, RJ, Wagner, C. Effect of dietary methyl group deficiency on folate metabolism in rats. J Nutr, 119(4), 618-21, 1989

Wagner, C, Decha-Umphai, W, Corbin, J. Phosphorylation modulates the activity of glycine N-methyltransferase, a folate binding protein. In vitro phosphorylation is inhibited by the natural folate ligand. J Biol Chem, 264(16), 9638-42, 1989

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