Tuning-Up Human Metabolism
Principal Investigator: Bruce Ames
Abstract: K05 Senior Scientist Grant (NCCAM). Ames has published more than 450 publications and consistently ranks among the top few hundred of the most-cited-scientists in all fields; honors include The National Medal of Science & The Japan Prize. Career as pioneer/leader in: gene-regulation; genetic toxicology; mutagenesis; cancer prevention; endogenous oxidants/antioxidants; nutrition and health; mitochondrial decay; and aging. Professor of the Graduate School at U.C. Berkeley. Senior Scientist, Children's Hospital of Oakland Research Institute, with large lab in a newly renovated building. Scientific focus: ramifications of a major review showing that about 50 different human genetic diseases due to a poorer binding affinity (Km) of the mutant enzyme for the coenzyme, can be remedied by feeding high dose B vitamins which raise levels of the corresponding coenzyme; many polymorphisms also have lowered affinity of enzyme for coenzyme. We propose to expand this Km concept by: 1) Testing the effectiveness of high dose B vitamins on phenotypes caused by polymorphisms that affect the Km of enzymes for coenzyme, e.g. homocysteine accumulation in MTHFR: riboflavin; alcohol intolerance in half of Asians: niacin. 2) Testing the effectiveness of other metabolites and micronutrients.3) Determining if mitochondrial oxidative decay with age causes enzymes to lose affinity for their coenzymes and if this can be ameliorated by feeding high doses of B vitamins. Previous results showed that high doses of key mitochondrial metabolites delay mitochondrial decay and involve Km. 4) Minimizing DNA damage and cancer by optimizing micronutrient levels, particularly in the elderly.
Funding Period: 2003-01-01 - 2005-12-31
more information: NIH RePORT
- An assay for uracil in human DNA at baseline: effect of marginal vitamin B6 deficiencySusan T Mashiyama
Department of Cell and Molecular Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720, U S A
Anal Biochem 372:21-31. 2008..The average concentration of DNA-uracil in these subjects was found to be approximately 3,000 uracils per diploid lymphocyte, which is comparable to steady state levels of one of the oxidative adducts of DNA, 8-oxoguanine...
- A simple assay for frequency of chromosome breaks and loss (micronuclei) by flow cytometry of human reticulocytesTal Offer
Nutritional Genomics Center, Children s Hospital of Oakland Research Institute, Oakland, California 94609, USA
FASEB J 19:485-7. 2005..This method, unlike available micronuclei assays, allows rapid evaluation of a large number of cells and therefore should prove to be useful in monitoring of human populations for genetic damage...
- An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioral functionJoyce C McCann
Nutrition and Metabolism Center, Children s Hospital Oakland Research Institute, Oakland, CA, USA
Am J Clin Nutr 85:931-45. 2007..In children >2 y of age and in adolescents with ID-A, evidence suggests cognitive or behavioral deficits; however, the surprisingly small number of studies conducted in either humans or animals prevents a thorough assessment...
- 5-Methyltetrahydrofolate inhibits photosensitization reactions and strand breaks in DNATal Offer
Nutrition and Metabolism Center, CHORI, Oakland, California, USA
FASEB J 21:2101-7. 2007..These observations suggest a new role for reduced folate in protection from ultraviolet damage and have bearing on the hypothesis that folate photodegradation influenced the evolution of human skin color...
- Biotin deficiency inhibits heme synthesis and impairs mitochondria in human lung fibroblastsHani Atamna
Nutrition and Metabolism Center, Children s Hospital Oakland Research Institute, Oakland, CA 94609, USA
J Nutr 137:25-30. 2007..The findings are discussed in relation to aging and birth defects in humans...
- Chronic ethanol perturbs testicular folate metabolism and dietary folate deficiency reduces sex hormone levels in the Yucatan micropigLynn M Wallock-Montelius
Children s Hospital Oakland Research Institute, Oakland, California 94609, and Department of Internal Medicine, University of California, Davis 95616, USA
Biol Reprod 76:455-65. 2007..Furthermore, methionine synthase may influence the hormonal regulation of spermatogenesis...
- Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageBruce N Ames
Nutrition and Metabolism Center, Children s Hospital of Oakland Research Institute, Oakland, CA 94609, USA
Proc Natl Acad Sci U S A 103:17589-94. 2006..A multivitamin-mineral supplement is one low-cost way to ensure intake of the Recommended Dietary Allowance of micronutrients throughout life...
- Oxidative stress and inflammation in iron-overloaded patients with beta-thalassaemia or sickle cell diseasePatrick B Walter
Children s Hospital Oakland Research Institute, Oakland, CA 94609, USA
Br J Haematol 135:254-63. 2006..This supports the hypothesis that the biology of SCD may show increased inflammation and increased levels of protective antioxidants compared with thalassaemia...
- An overview of evidence for a causal relationship between dietary availability of choline during development and cognitive function in offspringJoyce C McCann
Nutrition and Metabolism Center, Children s Hospital Oakland Research Institute, 5700 Martin Luther King Jr Way, Oakland, CA 94609 1673, USA
Neurosci Biobehav Rev 30:696-712. 2006..Discussion topics include methodological issues, such as the importance of independent replication, causal criteria, and uncertainties in interpreting test results...
- (R)-alpha-lipoic acid protects retinal pigment epithelial cells from oxidative damageLudmila A Voloboueva
Biophysics Graduate Group, University of California, Berkeley, USA
Invest Ophthalmol Vis Sci 46:4302-10. 2005..To determine whether (R)-alpha-lipoic acid (LA) protects cultured human fetal retinal pigment epithelial (hfRPE) cells against oxidative injury and identify the pathways that may mediate protection...
- Mineral and vitamin deficiencies can accelerate the mitochondrial decay of agingBruce N Ames
Nutrition, Metabolisms and Genomics Center, Children s Hospital Oakland Research Institute, Oakland, CA 94609, U States
Mol Aspects Med 26:363-78. 2005..An optimum intake of micronutrients could tune up metabolism and give a marked increase in health, particularly for the poor, elderly, and obese, at little cost...
- Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animalsJoyce C McCann
Nutrition, Metabolism and Genomics Center, Children s Hospital Oakland Research Institute, Oakland, CA 94609, USA
Am J Clin Nutr 82:281-95. 2005....
- Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitineJiangang Long
Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697 4540, USA
Neurochem Res 34:755-63. 2009....