Formation of trimethylamine from dietary choline by streptococcus sanguis I, which colonizes the mouth
Abstract
Choline is a component of the normal diet, and when humans ingest large amounts they excrete trimethylamine (which can impart a fishy body odor). In the presence of nitrite, trimethylamine can be converted to dimethylnitrosamine, a potent carcinogen. Bacteria in the large intestine metabolize choline to form trimethylamine. We determined that a bacterium normally present in the oral cavity also has this capacity. Mixed bacterial flora cultured from dental plaque and saliva converted choline to trimethylamine. The only organism with trimethylamine-forming capability isolated from these mixed cultures was identified as Streptococcus sanguis I (a facultative anaerobe). The other products formed when choline was cleaved were ethanol and acetate. The formation of trimethylamine by S. sanguis I was enzyme-mediated. Activity was destroyed by heating at 100 degrees C, and obeyed Michaelis-Menten kinetics (K(apparent) for choline = 184 +/- 58 microM; V(max apparent) = 1.7 +/- 0.1 micromol/mg protein/h). Activity was maximal at pH 7.5 to 8.5, was membrane-bound, and required a divalent metal cation (cobalt or iron). More trimethylamine was produced by bacteria incubated under a nitrogen than under an aerobic atmosphere. Activity was inhibited by deanol, betaine aldehyde, hemicholinium-3, iodoacetate, semicarbazide, and 2,4-dinitrophenol, and was enhanced by sulfhydryl-reducing agents (glutathione, 2-mercaptoethanol, DL-dithiothreitol) and sodium bisulfite. The enzyme activity that we describe in S. sanguis I is similar to that previously described in the anaerobic bacteria isolated from intestinal flora.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Oral flora Streptococcus sanguis can produce TMA from choline.
“oral flora (Streptococcus sanguis, a facultative anaerobe) also can form TMA from choline (25).”
From Trimethylamine <i>N</i> -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [25]
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Computational Handbook of Statistics.
Crofts, A., Bruning, J. L., & Kintz, B. L. (1969) · Journal of the American Statistical Association · doi:10.2307/2283756 · Cited by 2,339 · see citing works
A model for gastric cancer epidemiology
CORREA, P. (1975) · The Lancet · doi:10.1016/s0140-6736(75)90498-5 · Cited by 1,158 · see citing works
Formation of N-nitroso compounds: Chemistry, kinetics, and in vivo occurrence
Mirvish, S. S. (1975) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(75)90255-0 · Cited by 779 · see citing works
Molecular Biology of Osmoregulation
Rudulier, D. L., Strøm, A. R., Dandekar, A. M., et al. (1984) · Science · doi:10.1126/science.224.4653.1064 · Cited by 624 · see citing works
Spiegelhalder, B., Eisenbrand, G., & Preussmann, R. (1976) · Food and Cosmetics Toxicology · doi:10.1016/s0015-6264(76)80005-3 · Cited by 596 · see citing works
Relevance of nitrosamines to human cancer
Bartsch, H., & Montesano, R. (1984) · Carcinogenesis · doi:10.1093/carcin/5.11.1381 · Cited by 495 · see citing works
Physiological differentiation of viridans streptococci
Facklam, R. R. (1977) · Journal of Clinical Microbiology · doi:10.1128/jcm.5.2.184-201.1977 · Cited by 447 · see citing works
DIETARY CHOLINE: BIOCHEMISTRY, PHYSIOLOGY, AND PHARMACOLOGY
Zeisel, S. H. (1981) · Annual Review of Nutrition · doi:10.1146/annurev.nu.01.070181.000523 · Cited by 438 · see citing works
Self-citationThe effect of nitrate intake on nitrite formation in human saliva
Tannenbaum, S. R., Weisman, M., & Fett, D. (1976) · Food and Cosmetics Toxicology · doi:10.1016/s0015-6264(76)80006-5 · Cited by 381 · see citing works
Microbial population shifts in developing human dental plaque
Ritz, H. L. (1967) · Archives of Oral Biology · doi:10.1016/0003-9969(67)90190-2 · Cited by 342 · see citing works
The microbiota of the gingival crevice area of man—I
Socransky, S. S., Gibbons, R. J., Dale, A. C., Bortnick, L., Rosenthal, E. J. K., & Macdonald, J. B. (1963) · Archives of Oral Biology · doi:10.1016/0003-9969(63)90019-0 · Cited by 302 · see citing works
Formation of methylamines from ingested choline and lecithin.
Zeisel, S. H., Wishnok, J. S., & Blusztajn, J. K. (1983) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)33590-1 · Cited by 253 · see citing works
Self-citationConcentrative Accumulation of Choline by Human Erythrocytes
Martin, K. J. (1968) · The Journal of General Physiology · doi:10.1085/jgp.51.4.497 · Cited by 166 · see citing works
Trimethylamine metabolism in obligate and facultative methylotrophs
Colby, J., & Zatman, L. J. (1973) · Biochemical Journal · doi:10.1042/bj1320101 · Cited by 142 · see citing works
The Growth of Oral Bacteria on Saliva
Jong, M. H. D., & van der Hoeven, J. S. (1987) · Journal of Dental Research · doi:10.1177/00220345870660021901 · Cited by 136 · see citing works
Reaction of drugs with nitrous acid as a source of carcinogenic nitrosamines.
Lijinsky, W. (1974) · PubMed · Cited by 134 · see citing works
Normal plasma choline responses to ingested lecithin
Zeisel, S. H., Growdon, J. H., Wurtman, R. J., Magil, S. G., & Logue, M. P. (1980) · Neurology · doi:10.1212/wnl.30.11.1226 · Cited by 124 · see citing works
Self-citationPomfret, E. A., daCosta, K.-A., Schurman, L. L., & Zeisel, S. H. (1989) · Analytical Biochemistry · doi:10.1016/0003-2697(89)90091-2 · Cited by 122 · see citing works
Self-citationNitrosation of Tertiary Amines and Some Biologic Implications,
Lijinsky, W., Lk, K., Conrad, E., & de Bogart, R. V. (1972) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/49.5.1239 · Cited by 117 · see citing works
The Clostridial Fermentations of Choline and Ethanolamine
Bradbeer, C. (1965) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)97007-9 · Cited by 116 · see citing works
The origin of urinary dimethylamine
Asatoor, A. M., & Simeshoff, M. L. (1965) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(65)90048-6 · Cited by 107 · see citing works
Haubrich, D. R., & Gerber, N. H. (1981) · Biochemical Pharmacology · doi:10.1016/0006-2952(81)90265-3 · Cited by 97 · see citing works
The Clostridial Fermentations of Choline and Ethanolamine
Bradbeer, C. (1965) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)97008-0 · Cited by 97 · see citing works
Endogenous formation of dimethylamine
Zeisel, S. H., daCosta, K.-A., & Fox, J. G. (1985) · Biochemical Journal · doi:10.1042/bj2320403 · Cited by 93 · see citing works
Self-citationStephany, R. W., & Schuller, L. (2009) · Oncology · doi:10.1159/000225437 · Cited by 85 · see citing works
Constancy of glucose and starch fermentations by two different human faecal microbial communities.
Weaver, G. A., Krause, J. A., Miller, T. L., & Wolin, M. J. (1989) · Gut · doi:10.1136/gut.30.1.19 · Cited by 68 · see citing works
ANAEROBIC DEGRADATION OF CHOLINE I. , Vibrio cholinicus n. sp
Hayward, H. R., & Stadtman, T. C. (1959) · Journal of Bacteriology · doi:10.1128/jb.78.4.557-561.1959 · Cited by 68 · see citing works
Studies on accumulation and metabolic fate of [N-Me3H]choline in human term placenta fragments
Welsch, F. (1976) · Biochemical Pharmacology · doi:10.1016/0006-2952(76)90490-1 · Cited by 58 · see citing works
Degradation of various amine compounds by mesophilic clostridia
M�ller, B., Hippe, H., & Gottschalk, G. (1986) · Archives of Microbiology · doi:10.1007/bf00413032 · Cited by 50 · see citing works
Volatile N-nitrosamines in the urine of normal donors and of bladder cancer patients.
Kakizoe, T., Wang, T.-T., Eng, V., Furrer, R., Dion, P. W., & Bruce, W. R. (1979) · PubMed · Cited by 50 · see citing works
An in Vitro Study of Choline Uptake by Intestine from Neonatal and Adult Rats
Sheard, N. F., & Zeisel, S. H. (1986) · Pediatric Research · doi:10.1203/00006450-198608000-00014 · Cited by 44 · see citing works
Self-citation[45] Enzymatic determination of ethanol
Kaplan, N. O., & Ciotti, M. M. (1957) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(57)03385-6 · Cited by 43 · see citing works
Non‐oxidative demethylation of trimethylamine N‐oxide by Pseudomonas aminovorans
Large, P. J. (1971) · FEBS Letters · doi:10.1016/0014-5793(71)80470-2 · Cited by 41 · see citing works
Anaerobic Degradation of Choline
Hayward, H. R. (1960) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64514-4 · Cited by 40 · see citing works
Anaerobic Degradation of Choline
Hayward, H. R., & Stadtman, T. C. (1960) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)69563-8 · Cited by 34 · see citing works
Seim, H., Lõster, H., Claus, R., Kleber, H. ‐., & Strack, E. (1982) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1982.tb00060.x · Cited by 33 · see citing works
Evidence for the existence of separate transport mechanisms for choline and betaine in rat kidney
Sung, C. P., & Johnstone, R. M. (1969) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(69)90019-4 · Cited by 30 · see citing works
Action of Enterobacteriaceae on Choline and Related Compounds
Dyer, F. E., & Wood, A. J. (1947) · Journal of the Fisheries Research Board of Canada · doi:10.1139/f47-002 · Cited by 29 · see citing works
Deanol Affects Choline Metabolism in Peripheral Tissues of Mice
Haubrich, D. R., Gerber, N. H., & Pflueger, A. B. (1981) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1981.tb00480.x · Cited by 25 · see citing works
Johnson, K. A. (1977) · PubMed · Cited by 21 · see citing works
Aerobic degradation of choline by <i>Proteus mirabilis</i>: enzymatic requirements and pathway
Sandhu, S. S., & Chase Jr., T. (1986) · Canadian Journal of Microbiology · doi:10.1139/m86-135 · Cited by 18 · see citing works
de la Huerga, J., Pópper, H., & Steigmann, F. (1951) · PubMed · Cited by 17 · see citing works
EFFECTS OF 2‐DIMETHYLAMINOETHANOL (DEANOL) ON THE METABOLISM OF CHOLINE IN PLASMA
Ceder, G., Dahlberg, L., & Schuberth, J. (1978) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1978.tb10458.x · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme
Craciun, S., & Balskus, E. P. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215689109 · Cited by 701 · see citing works
Trimethylamine <i>N</i> -Oxide, the Microbiome, and Heart and Kidney Disease
Zeisel, S. H., & Warrier, M. (2017) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064732 · Cited by 475 · see citing works
Self-citationFennema, D., Phillips, I. R., & Shephard, E. A. (2016) · Drug Metabolism and Disposition · doi:10.1124/dmd.116.070615 · Cited by 355 · see citing works
Martínez-del Campo, A., Bodea, S., Hamer, H. A., Marks, J. A., Haiser, H. J., Turnbaugh, P. J., & Balskus, E. P. (2015) · mBio · doi:10.1128/mbio.00042-15 · Cited by 224 · see citing works
Ufnal, M., Jazwiec, R., Dadlez, M., Drapala, A., Sikora, M., & Skrzypecki, J. (2014) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2014.09.010 · Cited by 205 · see citing works
- Authors
- Chao, C.-K., & Zeisel, S. H.
- Affiliations
- Boston University (US)
- Corresponding author
- Zeisel, Steven H.
- ORCID
- Zeisel, Steven H.
- Venue
- The Journal of Nutritional Biochemistry
- Publisher
- Elsevier BV
- Published
- 1990-02
- Volume
- 1
- Issue
- 2
- Pages
- 89-97
- ISSN
- 0955-2863 (ISSN-L)
- OpenAlex
- W2057222589
- Cited by
- 23
- References
- 44
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2012: 1
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Nutritional Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial metabolism and enzyme function
- Keywords
- trimethylamine, choline metabolism, Streptococcus sanguinis, oral bacteria, dental plaque, saliva, trimethylamine N-oxide, N-nitrosodimethylamine, enzyme kinetics, dietary choline
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review