MEETING NEWS
Elizabeth Zubritsky reports from the ACS National Meeting—San Francisco
cysteine, they focused on sulfur amino acids (SAAs). These experiments had a modified crossover design that eliminated variability among individuDiet and time of day strongly als due to age, gender, race, genetics, influence metabolomic smoking habits, and so on; each person studies was essentially his or her own control. Dean Jones and colleagues at Emory The subjects spent 5 days on either a University’s School of Medicine have normal diet or a chemically defined put the adage “You are what you eat” to diet without SAAs and then 5 days on the test. They have run 1H-NMR spectra the same diet with SAAs. As before, of plasma samples collected throughplasma samples were collected and out the day from various subjects NMR spectra were analyzed. and can distinguish samples The spectra fell into four taken in the morning (while distinct classes: normal diet subjects are fasting and after without SAAs, normal diet breakfast) from those taken with SAAs, chemically defined in the afternoon or evening diet without SAAs, and chemi(when subjects have eaten two cally defined diet with SAAs. or more meals). In fact, they Thus, the influence of SAAs determined that the time of could be detected whether the day (i.e., time since last meal) subjects were on the chemiaccounted for 79% of the total cally modified or the normal variation in the NMR spectra, diet, though the chemically whereas only 21% correspondmodified diet simplified the ed to differences among indimetabolic profiles. viduals. The researchers also Encouraged by those manipulated the subjects’ diets results, the researchers and could group the spectra removed taurine, one of the on the basis of which diet the direct products of cysteine participants were fed. metabolism, from the spectra. “In a certain way, it’s preTaurine levels are maintained dictable that there would be remarkably well by the time-of-day variation,” Jones body, so one way to measure says. Researchers have concysteine intake is to look for ducted many studies that show taurine. But the team wanted how the levels of particular to see whether the metabolic Diet matters. What and when you eat influences your metabolomic nutrients change during the signature would indicate the profile. day. Knowing this, doctors presence or absence of cyswho want to measure analytes teine even without taurine. such as glucose collect samples while data. Both analyses yielded the same “Can things that aren’t direct products the patients are fasting. But Jones adds, three classifications: morning, aftergive us that information?” Jones asks. “I would never have expected that the noon-and-evening, and night. Indeed, when the researchers removed magnitude would be as great as it is.” The levels of lipids were among the taurine from the spectrum, the reJones’s group studies the link bebiggest differences in the profiles. That sponse to SAAs was still there. “The tween oxidative stress and human makes sense, Jones says, because, compower of chemistry here is the ability health. They are particularly interested pared with carbohydrates and amino to reliably measure so many different in glutathione and cysteine, a critiacids, lipids are slower to accumulate in chemicals to get a metabolic signature,” cal precursor of glutathione. Because and be cleared from the bloodstream. he says. cysteine is found in so many human The team’s ultimate goal is to find Jones knows that the search is just proteins, they needed a global methbiological response indicators that are beginning for biological response indiod—metabolomics—to look for links linked to environmental and dietary cators for various nutrients, chemicals, between the oxidation–reduction state exposures. Ideally, these indicators and enzymes. But he thinks that his of cysteine and disease. They chose 1Hwould remain long after a chemical is team has established a proof of prinNMR because it is comprehensive. cleared from the body, or conversely, ciple that this type of experiment can “All we were going to do is look at after a dietary deficiency has been rework. And he adds, “The classification the spectrum as a function of time of stored. Could an NMR spectrum reveal tells us . . . what we have to be conday and then compare that back to the deficiencies in the intake of a single cerned about when we start collecting measured change in the thiol/disulfide dietary component? samples for human metabolomics redox state,” says Jones. “At that point, Because of the group’s interest in studies.” PHOTOS.COM
I had no expectation of what we might see.” In the first experiment, Jones and colleagues took blood samples hourly from 8 subjects who were fed standardized meals at 9 a.m., 1 p.m., 6 p.m., and 10 p.m. A total of 200 samples were collected (25 time points per subject). The NMR spectra were subjected to both principal component analysis, which separates classes according to the differences, and k-means clustering, which groups together the most similar
3236 Journal of Proteome Research • Vol. 5, No. 12, 2006
