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oai:www.ideals.illinois.edu:2142/83711 2023-07-11 col_2142_5131 col_2142_14781 com_2142_5130 com_2142_687 com_2142_397

Nakamura, Manabu T. Strakova, Jana 2015-09-25T21:10:09Z 2015-09-25T21:10:09Z 10000-01-01 2008 2008 In mouse liver homogenates, 1000 mumol/L D,L-CBHcy did not inhibit methionine synthase, CBS and cystathionase activities but 5 mumol/L D,L-CBHcy completely inhibited BHMT activity indicating, that D,L-CBHcy was a specific inhibitor of BHMT. To address whether BHMT inhibition caused hyperhomocysteinemia, mice were injected with 1mg of D,L-CBHcy. This reduced BHMT activity (87%) and elevated total plasma Hcy (tHcy, 2.7-fold) for 8 hours. Repeated intraperitoneal injections of D,L-CBHcy (6 doses) additionally reduced the liver S-adenosylmethionine-to-S-adenosylhomocysteine ratio (65%). To assess whether BHMT inhibition affected liver and plasma amino acids, rats were fed 5mg D,L-CBHcy (9 doses). Plasma methionine and serine decreased (23 and 17%, respectively), while histidine, Hcy and glycine increased (35, 311 and 24% respectively). There were no changes in liver methionine and Hcy, but liver taurine, serine, and glutamate decreased (74, 50 and 46%, respectively). Increased plasma betaine (1465%) confirmed that BHMT was functionally inhibited in vivo. Interestingly, liver CBS activity and protein levels decreased (56 and 26%, respectively). To assess whether BHMT inhibition affected glutathione levels and/or caused fatty liver, rats were fed either an adequate (4.5g/kg methionine, 3.7g/kg cystine); cystine-devoid (4.5g/kg methionine, 0g/kg cystine) or a methionine-deficient diet (1.5g/kg methionine, 3.7g/kg cystine) alone or in combination with L-CBHcy for 3, 7 or 14 days. L-CBHcy treatment reduced liver glutathione in rats fed the adequate and cysteine-devoid diets. All animals fed the methionine-deficient diet with L-CBHcy developed fatty liver. L-CBHcy treatment decreased liver CBS activity (15--74%) and the effect was exacerbated with time. We conclude that BHMT activity is required for normal levels of plasma Hcy and methionine, liver SAM and glutathione, and CBS activity. Made available in DSpace on 2015-09-25T21:10:09Z (GMT). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 3314907.pdf: 1539890 bytes, checksum: aa0e6a889670aeb87b9859f78ab381b9 (MD5) Previous issue date: 2008 Embargo set by: Seth Robbins for item 84992 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs U of I Only 107 p. Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008. http://hdl.handle.net/2142/83711 (MiAaPQ)AAI3314907 eng Chemistry, Biochemistry Role of Betaine-Homocysteine S-Methyltransferase in Homocysteine Methylation text Food Science and Human Nutrition Food Science and Human Nutrition University of Illinois at Urbana-Champaign Dissertation Ph.D.