15N Metabolic Flux Analysis Service - Creative Proteomics Metabolomics

Q: What is the difference between 13C-MFA and 15N-MFA?

13C-MFA tracks carbon skeletons through glycolysis, the pentose phosphate pathway, and the TCA cycle to quantify energy generation and carbon partitioning. 15N-MFA tracks nitrogen atom economy, measuring inorganic ammonium assimilation, amino acid transamination cascades (GOT, GPT, PSAT1), the urea cycle, and de novo purine/pyrimidine nucleotide synthesis, which cannot be resolved by carbon tracing alone due to reversible transamination.

Q: Why is high mass resolving power critical for 15N isotopic analysis?

The mass difference between a 15N isotope (+0.99703 Da) and a 13C isotope (+1.00335 Da) is only 6.32 mDa. On low-resolution mass spectrometers, 15N and 13C peaks overlap, causing severe measurement errors. Our Orbitrap platforms operate at >140,000 FWHM resolving power, completely separating 15N from natural 13C isobars to ensure pure, accurate mass isotopologue distributions.

15N Metabolic Flux Analysis — Resolving Nitrogen Fate and Transamination Dynamics

Nitrogen is an indispensable elemental component of amino acids, purine and pyrimidine nucleotides, polyamines, glutathione, and neurotransmitters. However, because nitrogen atoms undergo rapid, reversible transamination across multiple transaminases (GOT/AST, GPT/ALT, PSAT1, BCAT) and deamination via glutamate dehydrogenase, nitrogen fluxes decouple from carbon skeleton trajectories and cannot be determined by carbon isotope tracing alone.

Stable isotope 15N metabolic flux analysis (15N-MFA) tracks the transfer and incorporation velocity of nitrogen atoms across complex biochemical networks to calculate in vivo reaction rates. As part of our comprehensive metabolic flux analysis service, targeted 15N-MFA provides quantitative resolution of cellular nitrogen economy. It enables you to:

(i) Differentiate amide-nitrogen versus amino-nitrogen allocation from glutamine into nucleotide synthesis versus non-essential amino acid transamination

(ii) Quantify inorganic ammonium assimilation efficiency via glutamate dehydrogenase (GLUD) and glutamine synthetase (GS)

(iii) Resolve hepatic ammonia detoxification capacity and urea cycle flux across carbamoyl phosphate synthetase 1 (CPS1), ornithine transcarbamylase (OTC), and argininosuccinate synthase (ASS1)

(iv) Track branched-chain amino acid (BCAA) nitrogen transfer to glutamate and alanine during metabolic stress, muscle wasting, and tumor progression.

What Analytical Challenges Do We Solve in 15N Fluxomics?

Key hurdles in nitrogen flux analysis include isobaric mass overlap between 15N (+0.9970 Da) and 13C (+1.00335 Da) isotopologues, extensive network reversibility in transamination, and rapid intracellular pool turnover. Creative Proteomics resolves these challenges with a dedicated 15N analytical workflow that is:

Isotopically Resolved: Leveraging high-resolution Orbitrap mass spectrometry (>140,000 FWHM) to baseline-resolve 15N isotopic mass defects from isobaric 13C, 2H, and 18O species without spectral interference.
Position-Specific: Employing distinct [amide-15N]glutamine, [alpha-15N]glutamine, [15N]glutamate, and [15N]ammonium tracers to isolate specific enzymatic transfer steps.
Quantitatively Constrained: Combining intracellular 15N mass isotopologue distributions (MIDs) with quantitative amino acid and ammonia uptake/secretion rates measured via targeted metabolomics panels to calculate absolute molar flux rates.
Model-Validated: Implementing Elementary Metabolic Unit (EMU) network algorithms adapted for nitrogen stoichiometry with Chi-square goodness-of-fit testing and 95% profile likelihood confidence intervals.

Targeted 15N Tracer Selection Strategies: Resolving Specific Nitrogen Nodes

Creative Proteomics offers a comprehensive range of 15N stable isotope tracer configurations tailored to specific metabolic decision points across mammalian, microbial, and plant systems.

1. Standard 15N-Glutamine Tracing Panels

Tracer Configuration	Target Pathway Resolution & Readout
[amide-¹⁵N]Glutamine (γ-Nitrogen)	Specifically tracks glutamine amidotransferase reactions. Labels carbamoyl phosphate for pyrimidine synthesis (CAD complex: M+1 UMP, CTP), PRPP amidotransferase for purine synthesis (M+1 IMP, AMP, GMP), and glucosamine-6-phosphate synthesis (GFPT1) without entering transamination cascades within our nucleotide metabolic flux analysis framework.
[α-¹⁵N]Glutamine (Amino-Nitrogen)	Follows deamidation to glutamate and subsequent transamination. Labels aspartate (via GOT1/2), alanine (via GPT1/2), serine (via PSAT1), and phosphoserine in our amino acid metabolic flux analysis workflow.
[U-¹⁵N₂]Glutamine (Dual Labeled)	Measures total glutamine nitrogen utilization, simultaneously capturing both amidotransferase flux (M+1 nucleotides) and transamination flux (M+1 amino acids, M+2 purines) to determine overall nitrogen economy.

2. Inorganic 15N-Ammonium & Amino Acid Tracing Panels

Tracer Configuration	Target Pathway Resolution & Readout
[¹⁵N]Ammonium ([¹⁵NH₄]Cl / [¹⁵NH₄]₂SO₄)	Measures de novo ammonia assimilation kinetics via GLUD (M+1 glutamate), GS (M+1 glutamine amide), and carbamoyl phosphate synthetase 1 (CPS1). Standard for microbial fermentation and plant nitrogen use efficiency.
[α-¹⁵N]Aspartate & [¹⁵N]Glutamate	Tracks direct amino group transfer into the urea cycle (argininosuccinate synthase flux) and purine ring synthesis (adenylosuccinate synthase flux) within our central carbon and nitrogen flux analysis module.
[¹⁵N]Glycine & [¹⁵N]Serine	Quantifies glycine incorporation into purine C4-C5-N7 cores, glutathione tripeptide synthesis (GSH), and one-carbon transfer dynamics in our one-carbon metabolic flux analysis.

3. Parallel & Dual 13C/15N Co-Tracing Panels

Panel Strategy	Key Applications & Network Constraints
Parallel [U-¹³C₆]Glucose + [α-¹⁵N]Glutamine	Independent labeling in parallel cultures fitted simultaneously in a unified stoichiometric model. Eliminates non-identifiability between carbon skeleton routing (glycolysis/TCA) and nitrogen transfer (transamination).
Dual-Labeled [U-¹³C₅, ¹⁵N₂]Glutamine	Directly monitors intact carbon-nitrogen bond conservation during glutaminolysis, resolving glutaminase deamidation rates versus intact transport and transamination.
Isotopically Nonstationary 15N-MFA (INST-MFA)	Applies short time-course sampling (seconds to minutes) to track rapid transamination transients in slow-growing cells and photosynthetic organisms via dynamic and INST metabolic flux analysis.

4. Customization & Add-ons

Category	Options
Custom Tracer Synthesis	Position-specific 15N, 13C/15N dual-labeled, or 18O-labeled precursors customized to client metabolic models
Nitrogen Boundary Rates	Quantitative measurement of extracellular ammonia, urea, glutamine, glutamate, and amino acid consumption/excretion rates
Compartmentalized Fluxes	Mitochondrial versus cytosolic transamination deconvolution via subcellular rapid fractionation
Complex Matrices	Adaptable extraction protocols for co-cultures, fermentation broths, plant root/leaf tissues, and biofluids

Why Choose Our 15N Metabolic Flux Analysis Service?

High-Resolution Mass Defect Resolution (>140,000 FWHM)
Ultra-high-resolution Orbitrap mass spectrometry baseline-resolves 15N (+0.99703 Da) from 13C (+1.00335 Da) isotopic peaks, eliminating isobaric overlap in complex biological matrices without derivatization artifacts.
Position-Specific Nitrogen Dissection
Targeted [amide-15N] versus [alpha-15N] glutamine strategies definitively separate amidotransferase-driven nucleotide synthesis from transaminase-driven amino acid pool replenishment.
Sub-Second Cryogenic Quenching Protocols
Rapid sub-zero organic solvent quenching (-80 °C) arrests fast enzymatic transamination within seconds, preserving true in vivo nitrogen isotopologue distributions of labile metabolites.
EMU Computational Modeling with Rigorous Statistics
Nitrogen transition networks are fitted using Elementary Metabolic Unit algorithms in INCA and 13CFLUX2, validated by Chi-square (χ²) goodness-of-fit testing and non-linear 95% profile likelihood confidence intervals.

Instrumentation & Method Parameters for 15N Isotopologue Profiling

Analytical Platform

High-Resolution LC-Orbitrap MS (Primary Platform)

Mass Spectrometer: Thermo Scientific Orbitrap Exploris 240 / 480 & Q-Exactive HF-X

Ionization Mode: Electrospray Ionization (ESI), Positive & Negative Polarity Switching

LC System: Vanquish Horizon UHPLC System

Chromatography: HILIC (SeQuant ZIC-pHILIC) & Reversed-Phase Ion-Pairing

Target Intermediates: Intact nucleotides (ATP, GTP, UTP, CTP, IMP), nucleotide sugars (UDP-GlcNAc), amino acids, urea cycle intermediates (citrulline, argininosuccinate, ornithine, arginine), and glutathione (GSH/GSSG)

Method Performance

Parameter	Typical Specification
Mass Resolving Power	Up to 240,000 FWHM at m/z 200
Mass Accuracy	< 1.5 ppm internal calibration
15N/13C Isobaric Separation	Baseline resolved (Δm = 6.32 mDa)
MID Analytical Precision	CV ≤ 1.5% across replicate injections
Linear Dynamic Range	3.5–4 orders of magnitude
Injection Volume	Typically 2–5 μL

GC-MS & High-Field 15N-NMR (Orthogonal Platforms)

GC-MS provides fragment-level positional verification for derivatized amino acids, while our NMR-based metabolic flux analysis platform provides non-destructive 15N-1H HMQC and 15N direct detection.

GC-MS Derivatization: TBDMS or chloroformate derivatization for amino acid backbone fragmentation
GC-MS Column: DB-5ms UI (30 m × 0.25 mm × 0.25 μm), EI 70 eV
15N-NMR System: Bruker Avance III HD 600 MHz Spectrometer equipped with cryoprobe for direct 15N tracking

Quality Control & Boundary Constraints

Spectral Quality Control: Retention time precision (CV < 0.5%), peak shape symmetry, and absence of detector saturation
Natural Abundance Correction: Mathematical subtraction of 15N natural abundance (0.366%) and background heavy isotopes via validated deconvolution matrices
Nitrogen Balance Constraints: Quantitative uptake (ammonia, amino acids) and excretion (urea, ammonia) rates utilized as fixed boundary conditions

Thermo Scientific Orbitrap Exploris High-Resolution LC-MS

Thermo Scientific Orbitrap Exploris (Figure from Thermo Fisher)

SCIEX Triple Quad™ 6500+ (Figure from Sciex)

Agilent 7890B / 5977B GC-MS (Figure from Agilent)

Bruker Avance III HD 600 MHz NMR Spectrometer

Bruker Avance III HD 600 MHz NMR (Figure from Bruker)

15N Metabolic Flux Analysis Workflow — A Step-by-Step Guide

Network Formulation & 15N Tracer Selection

We formulate the stoichiometric network of nitrogen atom transitions, selecting [amide-15N]glutamine, [alpha-15N]glutamine, or [15N]ammonium to ensure target transamination and nucleotide fluxes are mathematically identifiable.

Tracer Incubation & Sub-Second Cryogenic Quenching

Cells or microorganisms are labeled under validated growth conditions. Enzymatic transamination is arrested in sub-seconds using pre-cooled (-80 °C) organic solvents to prevent post-sampling nitrogen scrambling.

High-Resolution Mass Spectrometry Acquisition

15N mass isotopologue distributions of amino acids, nucleotides, and urea cycle intermediates are acquired via LC-Orbitrap MS. Culture media are analyzed for extracellular ammonia, urea, and amino acid exchange rates.

Mass Defect Deconvolution & Natural Abundance Correction

15N peaks are baseline-resolved from 13C isobars. Raw isotopologue intensities are mathematically corrected for natural 15N (0.366%) and background isotopic abundances using matrix deconvolution routines.

Computational Nitrogen Flux Modeling & Validation

Corrected MIDs and boundary rates are integrated into EMU nitrogen models. Net and exchange fluxes are fitted with Chi-square (χ²) goodness-of-fit testing and 95% profile likelihood confidence intervals.

How to Prepare and Submit Samples for 15N-MFA

Sample Type	Amount Required	Preparation & Quenching Instructions	Storage & Shipping
Adherent Mammalian Cells	1–10 × 10⁶ cells (e.g. 60/100 mm dish)	Aspirate medium (<3 s), rapid wash with ice-cold saline, add pre-cooled (-80 °C) 80:20 MeOH:H2O, scrape on dry ice. Avoid trypsinization. Retain parallel plate for cell count in mammalian cell metabolic flux analysis.	Store at −80 °C; ship on dry ice
Suspension Cells	2–10 × 10⁶ cells	Rapid cold centrifugation (4 °C, <2 min) or direct sub-zero buffered quenching (-40 °C). Avoid prolonged room-temperature washes.	Store at −80 °C; ship on dry ice
Microbial Broth / Fermentation	2–10 mg dry cell weight (OD-adjusted)	Fast vacuum filtration (<2 s) with immediate liquid nitrogen filter immersion, or cold methanol quenching for microbial metabolic flux analysis. Retain supernatant for ammonia/amino acid exchange analysis.	Store at −80 °C; ship on dry ice
Conditioned Media (Supernatant)	≥ 200 μL	Collect from matched labeling time points, centrifuge (10,000 × g, 5 min) to remove debris, aliquot supernatant for extracellular ammonia, glutamine, and urea quantification.	Store at −80 °C; ship on dry ice
Plant Tissues (Leaves / Roots)	20–100 mg wet weight	Instant freeze-clamping in liquid nitrogen, cryo-pulverization under liquid nitrogen conditions without thawing for plant metabolic flux analysis.	Store at −80 °C; ship on dry ice

Notes

Always retain parallel uncultured medium blanks and conditioned media to quantify extracellular nitrogen uptake and secretion rates
Do not use enzymatic detachment (trypsin) for adherent cultures; perform direct in-plate cold solvent quenching
Maintain continuous cold chain (−80 °C or dry ice) during sample storage and transport
Contact our technical team prior to collecting specialized or low-biomass matrices

Deliverables: What You Receive from 15N Metabolic Flux Analysis

Natural-Abundance-Corrected 15N MID Matrix: Fractional isotopic abundances (N+0 to N+n) for all target amino acids, nucleotides, and urea cycle intermediates (.csv / Excel).
Extracellular Nitrogen Exchange Rates: Calculated absolute consumption and secretion rates for glutamine, glutamate, ammonia, and urea (mmol/gDW/h or nmol/10⁶ cells/h).
Reaction Network & EMU Nitrogen Model Files: Complete stoichiometric equations, nitrogen atom transition matrices, and executable project files (.xml / INCA / 13CFLUX2).
Fitted Nitrogen Flux Values & Confidence Intervals: Estimated net (v_net) and exchange (v_xch) fluxes with 95% profile likelihood confidence intervals.
Statistical Diagnostics & Residuals: Chi-square (χ²) goodness-of-fit statistics, sum of squared residuals (SSR), and measured vs. simulated correlation plots.
Publication-Ready Nitrogen Flux Maps: High-resolution vector graphics (PDF/SVG) illustrating intracellular nitrogen distribution with flux-scaled arrow widths, supported by comprehensive fluxomics data analysis.

$15N Mass Isotopologue Distribution Bar Plot showing fractional nitrogen labeling across amino acids and nucleotides$

Representative 15N mass isotopologue distribution (MID) bar plot displaying natural-abundance-corrected fractional labeling (N+0 to N+3) across amino acids and nucleotide pools.

Quantitative Nitrogen Transamination and Biosynthetic Flux Map

Quantitative nitrogen metabolic flux map illustrating transamination networks, de novo nucleotide synthesis, and urea cycle rates with arrow widths scaled to absolute fluxes.

Profile likelihood confidence interval analysis demonstrating nonlinear 95% statistical boundaries and parameter identifiability for key transaminase and amidotransferase fluxes.

Statistical Goodness-of-Fit and Chi-Square Residual Diagnostics Plot for 15N Data

Statistical goodness-of-fit diagnostic plot showing measured versus simulated 15N MID correlation and weighted residual distribution with chi-square cutoff threshold.

Applications of 15N Metabolic Flux Analysis

Our 15N metabolic flux analysis service supports researchers across academic, biotechnology, and biopharma programs:

Cancer Metabolism & Nucleotide Synthesis

Quantify glutamine nitrogen addiction, CAD-mediated pyrimidine biosynthesis, and purine transamidation fueling rapid tumor cell proliferation

Microbial Nitrogen Economy & Bioprocess

Optimize inorganic ammonium uptake, eliminate nitrogen overflow into byproduct secretion, and maximize amino acid yield in industrial cell factories

Immunometabolism & T-Cell Dynamics

Track nitrogen rewiring governing polyamine synthesis, nitric oxide generation from arginine, and nucleotide expansion during effector T-cell activation

Urea Cycle Disorders & Hyperammonemia

Evaluate hepatic ammonia clearance capacity, resolve CPS1/OTC/ASS1 enzymatic bottlenecks, and investigate metabolic alterations in liver disease

Plant Nitrogen Use Efficiency (NUE)

Map nitrate and ammonium assimilation via the GS/GOGAT pathway and resolve nitrogen remobilization dynamics during crop stress and grain filling

Resolving Arginine Nitrogen Transamination and Urea Cycle Intermediates in Neuroinflammatory Disease Models

Journal: Journal of Neuroinflammation

Published: 2024

DOI: https://doi.org/10.1186/s12974-024-03038-2

Background

Arginine is a central nitrogen hub utilized for protein translation, nitric oxide (NO) generation, polyamine synthesis, and urea cycle transamination. In neurodegenerative and neuroinflammatory pathologies such as Huntington's disease (HD), hyperactive nitrogen metabolism and inducible nitric oxide synthase (iNOS) activation generate excessive reactive nitrogen species (RNS) and nitrosative stress. To elucidate how cellular nitrogen fluxes through arginine and urea cycle intermediates are altered in HD astrocytes and neuronal models, researchers performed quantitative targeted metabolomic profiling.

Challenge:

Quantify intracellular nitrogen-containing urea cycle metabolites (arginine, citrulline, ornithine) with high precision and determine how solute carrier transporter SLC7A2 modulation affects nitrogen flux into nitric oxide production versus transamination pathways.

Findings (from the published study)

Selective Nitrogen Transporter Upregulation: SLC7A2, a high-affinity cationic amino acid transporter supplying arginine nitrogen, was selectively upregulated in HD cellular models and patient tissues.
Hyperactive Nitrosative Flux: Inflammatory cytokine stimulation (IFN-γ/LPS) triggered heightened iNOS induction and excessive NO flux in HD cells, leading to downstream S-nitrosylation of mitochondrial fission proteins (DRP-1) and mitochondrial fragmentation.
Urea Cycle Flux Disruption: Quantitative HPLC-MS/MS profiling of urea cycle metabolites revealed that genetic knockout of SLC7A2 or extracellular arginine deprivation completely abolished pathological NO production and normalized nitrogen partitioning.
Therapeutic Validation: Modulating nitrogen substrate availability and urea cycle intermediate balance successfully protected mitochondrial morphology and attenuated inflammatory neurotoxicity.

Figure 4. Quantitative measurement of arginine and urea cycle nitrogen metabolites following inflammatory stimulation

Figure 4. Quantitative measurement of arginine and urea cycle nitrogen metabolites Figure 6. Schematic pathway of arginine nitrogen flux into nitric oxide synthesis versus urea cycle transamination

Figure 6. Schematic pathway of arginine nitrogen flux and transamination

Process Insight

This study demonstrates how quantitative mass spectrometry of nitrogen-containing metabolites resolves complex transamination and nitrogen partitioning mechanisms, linking specific amino acid transporter expression to downstream nitrosative flux and organelle pathology.

Where Our 15N Metabolic Flux Analysis Service Fits

Creative Proteomics performed the quantitative mass spectrometry workflow for urea cycle and nitrogen-containing metabolites in this study, delivering end-to-end analytical support:

Nitrogen Pathway Metabolite Quantification: Targeted HPLC-MS/MS assay with stable isotope internal standards for absolute quantification of arginine, citrulline, and ornithine.
Sub-Second Quenching & Extraction: Standardized cell harvesting protocols minimizing post-sampling enzymatic transamination.
Pathway Flux Interpretation: High-precision chromatographic deconvolution supporting biomedical insights into nitrogen metabolic rewiring.

Reference

Gaudet ID, Xu H, Gordon E, et al. Elevated SLC7A2 expression is associated with an abnormal neuroinflammatory response and nitrosative stress in Huntington’s disease. Journal of Neuroinflammation. 2024;21(1):38.

What is the difference between 13C-MFA and 15N-MFA?

13C-MFA tracks carbon skeletons through glycolysis, the pentose phosphate pathway, and the TCA cycle to quantify energy generation and carbon partitioning. 15N-MFA tracks nitrogen atom economy, measuring inorganic ammonium assimilation, amino acid transamination cascades (GOT, GPT, PSAT1), the urea cycle, and de novo purine/pyrimidine nucleotide synthesis, which cannot be resolved by carbon tracing alone due to reversible transamination.

Why is high mass resolving power critical for 15N isotopic analysis?

The mass difference between a 15N isotope (+0.99703 Da) and a 13C isotope (+1.00335 Da) is only 6.32 mDa. On low-resolution mass spectrometers, 15N and 13C peaks overlap, causing severe measurement errors. Our Orbitrap platforms operate at >140,000 FWHM resolving power, completely separating 15N from natural 13C isobars to ensure pure, accurate mass isotopologue distributions.

How do I choose between [amide-15N]glutamine and [alpha-15N]glutamine?

[amide-15N]glutamine specifically labels the gamma-amido nitrogen, which fuels amidotransferase reactions in purine (PRPP to IMP), pyrimidine (CAD complex to UMP), and hexosamine (GFPT1) biosynthesis. [alpha-15N]glutamine labels the alpha-amino nitrogen, which is transferred via transaminases (GOT1/2, GPT1/2, PSAT1) to alpha-keto acids to synthesize non-essential amino acids (aspartate, alanine, phosphoserine).

Can 15N-MFA resolve bidirectional transamination rates?

Yes. Reversible transamination reactions (e.g. glutamate + oxaloacetate <=> alpha-ketoglutarate + aspartate) create rapid nitrogen exchange. By measuring 15N labeling kinetics across donor-acceptor pairs and applying Elementary Metabolic Unit (EMU) algorithms with profile likelihood confidence intervals, we calculate both net flux (v_net) and bidirectional exchange flux (v_xch).

How do you prevent post-sampling nitrogen scrambling?

Aminotransferases maintain high enzymatic activity in cell lysates if not rapidly inactivated. We utilize sub-second cryogenic quenching with pre-cooled (-80 °C) organic solvents (80:20 methanol:water) directly on culture plates, avoiding trypsinization and room-temperature washes to preserve accurate in vivo 15N labeling states.

What is the advantage of dual 13C and 15N co-tracing?

Dual 13C/15N co-tracing (such as [U-13C6]glucose + [alpha-15N]glutamine or [U-13C5, 15N2]glutamine) simultaneously resolves carbon skeleton fueling and nitrogen transfer within a single experimental framework, providing complete stoichiometric coupling for investigating protein turnover, amino acid overflow, and metabolic reprogramming.

What software and statistical validation methods are applied to 15N flux datasets?

Flux modeling is executed in INCA and 13CFLUX2 adapted for nitrogen atom transitions. Model goodness-of-fit is validated by Chi-square (χ²) testing and residual analysis, while non-linear 95% confidence intervals are evaluated using Profile Likelihood methods to ensure all estimated nitrogen fluxes are mathematically identifiable.

Elevated SLC7A2 expression is associated with an abnormal neuroinflammatory response and nitrosative stress in Huntington's disease

Gaudet, I. D., Xu, H., Gordon, E., Cannestro, G. A., Lu, M. L., & Wei, J.

Journal: Journal of Neuroinflammation

Year: 2024

DOI: https://doi.org/10.1186/s12974-024-03038-2

Polyamine metabolism impacts T cell dysfunction in the oral mucosa of people living with HIV

Mahalingam, S. S., Jayaraman, S., Bhaskaran, N., Schneider, E., Faddoul, F., Paes Da Silva, A., ... & Pandiyan, P.

Journal: Nature Communications

Year: 2023

DOI: https://doi.org/10.1038/s41467-023-36163-2

Cancer SLC43A2 alters T cell methionine metabolism and histone methylation

Bian, Y., Li, W., Kremer, D. M., Sajjakulnukit, P., Li, S., Crespo, J., ... & Zou, W.

Journal: Nature

Year: 2020

DOI: https://doi.org/10.1038/s41586-020-2682-1

Suppression of the KRAS-NRF2 axis shifts arginine into the phosphocreatine energy system in pancreatic cancer cells

Di Giorgio, E., Choudhary, H., Ferino, A., Cortolezzis, Y., Dalla, E., D’Este, F., ... & Xodo, L. E.

Journal: iScience

Year: 2023

DOI: https://doi.org/10.1016/j.isci.2023.108566

Teriflunomide/leflunomide synergize with chemotherapeutics by decreasing mitochondrial fragmentation via DRP1 in SCLC

Mirzapoiazova, T., Tseng, L., Mambetsariev, B., Li, H., Lou, C. H., Pozhitkov, A., ... & Salgia, R.