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1 Author: Robert Lyons, Ph.D., 008 License: Unless otherwise noted, this material is made available under the terms of the reative ommons Attribution Share Alike.0 License: We have reviewed this material in accordance with U.S. opyright Law and have tried to maximize your ability to use, share, and adapt it. The citation key on the following slide provides information about how you may share and adapt this material. opyright holders of content included in this material should contact with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit Any medical information in this material is intended to inform and educate and is not a tool for selfdiagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
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3 M1 Renal: Folate Metabolism Dr. Robert Lyons Assistant Professor, Biological hemistry Director, DA Sequencing ore Web: Fall 008
4 Amino Acid metabolism Amino acids Folate metabolism Glu, Gln, Asp, Methylene TF Met ycle Urea oxaloacetate P u rin e s DA RA P y rim id in e s TA ycle fumarate Uric Acid (energy) ucleic Acid metabolism
5 Folate ( nearbon ) Pathways lick on any blue box to see details (Start with the section with Diet and follow the paths with red arrows) MethylTF onnects to Amino Acids Donation of one carbon (from Ser, Gly) MethyleneTF TF ycle Methionine ycle TF TF Diet: DF DF FormylTF Folate Folate onnects to ucleic Acids lectures Purine biosynthesis Thymidylate synthetase
6 Folic Acid is Synthesized By Bacteria ( ) n Paraaminobenzoic acid (PABA) S sulfanilamide Dietary folate: folic acid (meats, green veggies) *requires* the intestinal enzyme onjugase for absorption.
7 F ol ic ac id ( ) n ADP Di hy d ro fo l at e ADP ( ) n ADP T et ra hy d ro fo la te ADP ( ) n
8 F ol ic ac id ( ) n ADP Di hy d ro fo l at e ADP ( ) n ADP T et ra hy d ro fo la te ADP ( Inhibitors of DFR are important therapeutics: Methotrexate chemotherapy Trimethoprim inhibits bacterial DFR Pyrimethamine inhibits malarial DFR ) n
9 Tetrahydrofolate (et c) seri ne glycine (etc) 5, 10 methylene Tetrahydrofolate (et c) glycine AD 4 AD (etc) 5, 10 methylene
10 5 methyl AD Biosynthesis of methionine Gly Ser AD 5, 10 methylene ADP Biosynthesis of thymidylate 5, 10 methenyl ADP 10 formyl Biosyntheses purines of (et c) 5 methyl (et c) 10 formyl
11 S () Methionine () ATP PPi Pi () S Adenine () () SAdenosyl Methionine Methionine ycle And Biological Methyl Groups 5 methyl S () () omocysteine Bios ynthetic Methylation reaction S () Adenine Methyl acceptor * see examples Methylated acceptor () () SAdenosyl omocysteine () () Serine S () () ysteine (remainder of homocysteine degraded for energy)
12 5 methyl TF TF S homocysteine vitamin B 1 S meth ionine
13 (etc) Tetrahydrofolate arbon donor (e.g. serine or glycine) (etc) 5, 10 methylene meth ionine AD homocyste ine (etc) 5 methyl AD
14 S ATP PP i Pi S adeni ne Methionine SAdenosyl methionine orepinephrine SAM SA Epinephrine ther methyl acceptors: DA ( pg Islands ) RA
15 AD AD carb on dono r 5 methyl TF TF S homocysteine Adenosine vitamin B 1 meth ionine S ATP PP i P i S S adeno syl h omocys teine adenin e meth yl group don ated to bio logical sub strate S Sad enosyl meth ionine a denine
16 5 methyl AD Biosynthesis of methionine Gly Ser 5, 10 methylene ADP AD Biosynthesis of thymidylate 5, 10 methenyl ADP 10 formyl Biosyntheses purines Folate Deficiencies: Symptom: megaloblastic anemia Dietary deficiency: ommon especially in developing countries, lower socioeconomic classes of
17 Folate deficiency secondary to bowel irritation: onjugase is essential for adequate absorption of dietary folates onjugase production may be compromised by bowel irritation: Tropical Sprue bowel irritation probably arising from bacterial origin, causes intestinal inflamation and malabsorption. eliac Sprue similar outcome, but the original irritation is due to an allergic response, for example to gliaden (a component in gluten)
18 Folate Deficiency Secondary to B1 deficiency: the methyl trap hypothesis other TF reactions 5 methyl Biosynthesis of Methionine AD AD 5 10, methylene TF carbon donor 5, 10 methylene 10 formyl Biosynthesis of Thymidylate Biosyntheses Purines of 5 methyl TF TF homocysteine B 1 methionine B1 is also critical in other reactions, ones for which the deficiency has serious neurological consequences.
19 Additional Source Information for more information see: Slide 4: Robert Lyons Slide 5: Robert Lyons Slide 6: Robert Lyons Slide 7: Robert Lyons Slide 8: Robert Lyons Slide 9: Robert Lyons Slide 10: Robert Lyons Slide 11: Robert Lyons Slide 1: Robert Lyons Slide 1: Robert Lyons Slide 15: Robert Lyons Slide 16: Robert Lyons Slide 18: Robert Lyons
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M1 - Renal, Fall 2007
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Author(s): Seetha Monrad, M.D., 2009 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 License: http://creativecommons.org/licenses/by-nc-sa/3.0/
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Author(s): Roger Grekin, M.D., 2009 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 License: http://creativecommons.org/licenses/by-nc-sa/3.0/
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Figure 1. Stepwise approach of treating patients with rheumatoid arthritis.
Establish diagnosis early Document baseline disease activity and damage Estimate prognosis Initiate therapy Begin patient education Start DMARD therapy within 3 months Consider NSAID Consider local or
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Project: Ghana Emergency Medicine Collaborative Document Title: Approach to the Dyspenic Adult Patient Author(s): Randall Ellis, MD MPH (Vanderbilt University) License: Unless otherwise noted, this material
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