Sheng Hui
Harvard University
ProteomePhysicsGlass transitionInternal medicineEndocrinologyPairingNutrientExtreme value theorySystems biologyFlux (metabolism)Citric acid cycleAdipose tissueFluxomicsEnzymeChemistryCofactorGlycolysisAsparagineNicotinamide adenine dinucleotideKetogenic dietEssential amino acidAsparaginaseOverflow metabolismGlutamineNicotinamideExponentExtracellularQuantification methodsStackingProtein biosynthesisLogarithmPhase (matter)ProteomicsAmino acidGeneticsBiochemistryMetabolismGround stateComputational biologyNAD+ kinaseBiologyCatabolism
25Publications
12H-index
1,987Citations
Publications 17
Newest
#1Yujue Wang (RU: Rutgers University)H-Index: 4
#2Sheng Hui (Harvard University)H-Index: 12
Last. Xiaoyang Su (RU: Rutgers University)H-Index: 22
view all 4 authors...
Metabolic flux analysis (MFA) aims at revealing the metabolic reaction rates in a complex biochemical network. To do so, MFA uses the input of stable isotope labeling patterns of the intracellular metabolites. Elementary metabolic unit (EMU) is the computational framework to simulate the metabolite labeling patterns in a network, which was originally designed for simulating mass isotopomer distributions (MIDs) at the MS1 level. Recently, the EMU framework is expanded to simulate tandem mass spec...
1 CitationsSource
#1Tara TeSlaa (UW: University of Washington)H-Index: 15
#2Caroline Bartman (UW: University of Washington)H-Index: 11
Last. Joshua D. Rabinowitz (UW: University of Washington)H-Index: 100
view all 10 authors...
Glycolysis plays a central role in organismal metabolism, but its quantitative inputs across mammalian tissues remain unclear. Here we use 13C-tracing in mice to quantify glycolytic intermediate sources: circulating glucose, intra-tissue glycogen, and circulating gluconeogenic precursors. Circulating glucose is the main source of circulating lactate, the primary end product of tissue glycolysis. Yet circulating glucose highly labels glycolytic intermediates in only a few tissues: blood, spleen, ...
14 CitationsSource
#1Sheng Hui (Harvard University)H-Index: 12
#2Alexis J. Cowan (UW: University of Washington)H-Index: 5
Last. Joshua D. Rabinowitz (UW: University of Washington)H-Index: 100
view all 14 authors...
Summary Mammalian organs are nourished by nutrients carried by the blood circulation. These nutrients originate from diet and internal stores, and can undergo various interconversions before their eventual use as tissue fuel. Here we develop isotope tracing, mass spectrometry, and mathematical analysis methods to determine the direct sources of circulating nutrients, their interconversion rates, and eventual tissue-specific contributions to TCA cycle metabolism. Experiments with fifteen nutrient...
35 CitationsSource
#1Cholsoon Jang (Princeton University)H-Index: 29
#2Sheng Hui (Princeton University)H-Index: 12
Last. Joshua D. Rabinowitz (Princeton University)H-Index: 100
view all 19 authors...
Summary Mammalian organs continually exchange metabolites via circulation, but systems-level analysis of this shuttling process is lacking. Here, we compared, in fasted pigs, metabolite concentrations in arterial blood versus draining venous blood from 11 organs. Greater than 90% of metabolites showed arterial-venous differences across at least one organ. Surprisingly, the liver and kidneys released not only glucose but also amino acids, both of which were consumed primarily by the intestine and...
56 CitationsSource
#1Michael D. Neinast (UPenn: University of Pennsylvania)H-Index: 12
#2Cholsoon Jang (Princeton University)H-Index: 29
Last. Zoltan Arany (UPenn: University of Pennsylvania)H-Index: 48
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Summary Elevations in branched-chain amino acids (BCAAs) associate with numerous systemic diseases, including cancer, diabetes, and heart failure. However, an integrated understanding of whole-body BCAA metabolism remains lacking. Here, we employ in vivo isotopic tracing to systemically quantify BCAA oxidation in healthy and insulin-resistant mice. We find that most tissues rapidly oxidize BCAAs into the tricarboxylic acid (TCA) cycle, with the greatest quantity occurring in muscle, brown fat, l...
123 CitationsSource
The molecule succinate, which is a product of metabolism, promotes heat production and therefore calorie burning in brown fat in mice. This discovery could have implications for combating obesity in humans. The molecule succinate, which is a product of metabolism, promotes heat production and therefore calorie burning in brown fat in mice. This discovery could have implications for combating obesity in humans.
7 CitationsSource
Summary The redox cofactor nicotinamide adenine dinucleotide (NAD) plays a central role in metabolism and is a substrate for signaling enzymes including poly-ADP-ribose-polymerases (PARPs) and sirtuins. NAD concentration falls during aging, which has triggered intense interest in strategies to boost NAD levels. A limitation in understanding NAD metabolism has been reliance on concentration measurements. Here, we present isotope-tracer methods for NAD flux quantitation. In cell lines, NAD was mad...
160 CitationsSource
#1Natalya N. Pavlova (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 11
#2Sheng Hui (Princeton University)H-Index: 12
Last. Ji Zhang (IU: Indiana University)H-Index: 18
view all 9 authors...
Summary When mammalian cells are deprived of glutamine, exogenous asparagine rescues cell survival and growth. Here we report that this rescue results from use of asparagine in protein synthesis. All mammalian cell lines tested lacked cytosolic asparaginase activity and could not utilize asparagine to produce other amino acids or biosynthetic intermediates. Instead, most glutamine-deprived cell lines are capable of sufficient glutamine synthesis to maintain essential amino acid uptake and produc...
105 CitationsSource
#1Cholsoon Jang (Princeton University)H-Index: 29
#2Sheng Hui (Princeton University)H-Index: 12
Last. Joshua D. Rabinowitz (Princeton University)H-Index: 100
view all 10 authors...
Summary Excessive consumption of sweets is a risk factor for metabolic syndrome. A major chemical feature of sweets is fructose. Despite strong ties between fructose and disease, the metabolic fate of fructose in mammals remains incompletely understood. Here we use isotope tracing and mass spectrometry to track the fate of glucose and fructose carbons in vivo , finding that dietary fructose is cleared by the small intestine. Clearance requires the fructose-phosphorylating enzyme ketohexokinase. ...
243 CitationsSource
#1Wenyun Lu (Princeton University)H-Index: 38
#2Lin Wang (Princeton University)H-Index: 14
Last. Joshua D. Rabinowitz (Princeton University)H-Index: 100
view all 5 authors...
Abstract Aims: Accurate analysis of dinucleotide redox cofactors nicotinamide adenine dinucleotide phosphate reduced (NADPH), nicotinamide adenine dinucleotide phosphate (NADP+), nicotinamide adenine dinucleotide reduced (NADH), and nicotinamide adenine dinucleotide (NAD+) from biological samples is important to understanding cellular redox homeostasis. In this study, we aimed to develop a simple protocol for quenching metabolism and extracting NADPH that avoids interconversion among the reduced...
69 CitationsSource