PMID: 11916749Mar 28, 2002Paper

High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms

The American Journal of Clinical Nutrition
Bruce N AmesEli A Silver

Abstract

As many as one-third of mutations in a gene result in the corresponding enzyme having an increased Michaelis constant, or K(m), (decreased binding affinity) for a coenzyme, resulting in a lower rate of reaction. About 50 human genetic dis-eases due to defective enzymes can be remedied or ameliorated by the administration of high doses of the vitamin component of the corresponding coenzyme, which at least partially restores enzymatic activity. Several single-nucleotide polymorphisms, in which the variant amino acid reduces coenzyme binding and thus enzymatic activity, are likely to be remediable by raising cellular concentrations of the cofactor through high-dose vitamin therapy. Some examples include the alanine-to-valine substitution at codon 222 (Ala222-->Val) [DNA: C-to-T substitution at nucleo-tide 677 (677C-->T)] in methylenetetrahydrofolate reductase (NADPH) and the cofactor FAD (in relation to cardiovascular disease, migraines, and rages), the Pro187-->Ser (DNA: 609C-->T) mutation in NAD(P):quinone oxidoreductase 1 [NAD(P)H dehy-drogenase (quinone)] and FAD (in relation to cancer), the Ala44-->Gly (DNA: 131C-->G) mutation in glucose-6-phosphate 1-dehydrogenase and NADP (in relation to favism and hemolytic anemia), and th...Continue Reading

References

Oct 10, 1977·Biochemical and Biophysical Research Communications·H F Willard, L E Rosenberg
Apr 3, 1978·Clinica Chimica Acta; International Journal of Clinical Chemistry·G MorrowD T Whelan
Mar 1, 1975·Pediatric Research·T L PerryE Jellum
Apr 1, 1978·The American Journal of Psychiatry·B RimlandP Dreyfus
May 1, 1979·British Journal of Haematology·L Konopka, A V Hoffbrand
Feb 1, 1977·The American Journal of Clinical Nutrition·P B AcostaM Williamson
Jun 1, 1977·Journal of Pharmaceutical Sciences·H Bechgaard, S Jespersen
Oct 16, 1975·The New England Journal of Medicine·R W Erbe
Mar 1, 1992·Journal of Neurology, Neurosurgery, and Psychiatry·W J TriggsL J Willmore
May 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·P D CotterD F Bishop
Jan 1, 1992·European Journal of Clinical Pharmacology·M J Royer-MorrotR J Royer
Jun 1, 1992·Biochemical Medicine and Metabolic Biology·S L SillaotsD S Rosenblatt
Apr 1, 1992·Trends in Genetics : TIG·T VulliamyL Luzzatto
May 1, 1991·Biological Psychiatry·J Kleijnen, P Knipschild
Jan 1, 1991·Journal of Inherited Metabolic Disease·H D BakkerJ Lam
Apr 25, 1991·The New England Journal of Medicine·R ClarkeI Graham
Jan 1, 1990·Journal of Inherited Metabolic Disease·S YamaguchiT Hashimoto
Jun 1, 1990·Developmental Medicine and Child Neurology·V GriebelW Paulus
Feb 1, 1990·The American Journal of Clinical Nutrition·G J Fosmire
Mar 1, 1989·The Journal of Pediatrics·C Borgna-PignattiC Patrini
Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·A HironoE Beutler
Aug 1, 1989·Annals of Emergency Medicine·K D WrennC M Slovis
May 1, 1988·The British Journal of Dermatology·S Handfield-JonesR Peachey
Jul 1, 1986·The Journal of Clinical Endocrinology and Metabolism·S CastellsS J Marx

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Citations

Dec 24, 2002·The Journal of Biological Chemistry·Bruce N Ames
May 25, 2007·Food and Nutrition Bulletin·Patrick J Stover
Jan 24, 2008·Journal of Evaluation in Clinical Practice·Stephen J Genuis
Nov 25, 2011·The Journal of Alternative and Complementary Medicine : Research on Paradigm, Practice, and Policy·Julia J RucklidgeJeanette Johnstone
Jan 27, 2012·The American Journal of Clinical Nutrition·Carol P WilsonJohn M Scott
Aug 3, 2013·Journal of Psychoactive Drugs·Rachel HarrisonNeville Blampied
Sep 5, 2002·Nature Reviews. Cancer·Bruce N Ames, Patricia Wakimoto
Jan 15, 2005·Nutrition Journal·Mary Makowske, Richard D Feinman
Feb 11, 2005·Current Opinion in Gastroenterology·David H Alpers
Jan 17, 2004·Physiological Genomics·Jim Kaput, Raymond L Rodriguez
May 15, 2009·International Journal of Environmental Research and Public Health·Paul Clayton, Judith Rowbotham
Apr 7, 2009·Expert Review of Neurotherapeutics·Julia J RucklidgeBonnie J Kaplan
Jun 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nicholas J MariniJasper Rine
Mar 5, 2010·The Journal of Clinical Investigation·Christopher P CorpeMark Levine
Aug 1, 2012·Drug Delivery and Translational Research·Jaspreet Singh KochharLifeng Kang
Dec 17, 2016·Journal of Cellular Biochemistry·Avisek MajumderSuresh C Tyagi
Jan 27, 2018·Applied Biochemistry and Biotechnology·Senwen DengJia Zeng
Jun 8, 2002·Pharmacogenomics·Cornelia M UlrichRachel Sparks
Jun 11, 2005·São Paulo Medical Journal = Revista Paulista De Medicina·Marilena OshiroOrlando Cesar de Oliveira Barretto
Aug 21, 2009·The American Journal of Clinical Nutrition·Joyce C McCann, Bruce N Ames
Jul 13, 2004·Annals of the New York Academy of Sciences·Bruce N Ames
Aug 10, 2007·Antioxidants & Redox Signaling·Gary E Gibson, John P Blass
Apr 27, 2010·Journal of Child and Adolescent Psychopharmacology·Lewis Mehl-MadronaBonnie J Kaplan
Feb 15, 2013·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Marco ScottiPatrick J Stover

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