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Cited by 96Metabolomics and Mass Spectrometry StudiesMicrobial Metabolic Engineering and BioproductionMass Spectrometry Techniques and Applications

New stable isotope–mass spectrometric techniques for measuring fluxes through intact metabolic pathways in mammalian systems: introduction of moving pictures into functional genomics and biochemical phenotyping

Hellerstein, Marc K·2004·Metabolic Engineering
DOI 10.1016/j.ymben.2003.10.005
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Abstract

The thesis of this review is that fully assembled metabolic pathways in living systems, rather than genes or proteins, are the true units of function in biology and biochemistry. A corollary is that measurement of metabolic fluxes (biochemical kinetics) is thereby required to understand biochemical control and gene function. Recent methodologic advances for improving observability of metabolic pathway fluxes in vivo are reviewed. Stable isotope-mass spectrometric techniques discussed here include mass isotopomer distribution analysis (combinatorial analysis), for measurement of polymerization biosynthesis; 2H(2)O administration, for measuring synthesis of DNA (i.e., cell proliferation), RNA, proteins, lipids, glycolipids and other classes of molecules; non-invasive probes of intracellular metabolism, by sampling secreted metabolites in accessible body fluids, after isotopic labeling of the intracellular pathway; and measurement of multiple molecular fluxes concurrently, particularly through use of 2H(2)O. Examples are given of pathway fluxes measured by each of these techniques, noting the often-surprising results. It is concluded that the introduction of "moving pictures" as tools for biochemical phenotyping could radically alter many signature areas of contemporary biology, including functional genomics, drug discovery and development, and disease research.

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Authors
Hellerstein, M. K.
Affiliations
University of California, San Francisco (US)
Corresponding author
Hellerstein, Marc K
ORCID
Hellerstein, Marc K
Venue
Metabolic Engineering
Publisher
Elsevier BV
Published
2004-01
Volume
6
Issue
1
Pages
85-100
ISSN
1096-7176 (ISSN-L)
DOI
10.1016/j.ymben.2003.10.005
OpenAlex
W1965719377
Cited by
96
References
36
Citations by year
2025: 1 · 2024: 2 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 3 · 2014: 2 · 2013: 6 · 2012: 7
FWCI
3.08
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Metabolic Engineering (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
Keywords
metabolic flux measurement, stable isotope labeling, mass isotopomer distribution analysis, functional genomics, cell proliferation, secreted metabolites, cellular metabolism, biochemical kinetics, drug discovery, disease research
MeSH terms
Algorithms, Animals, Diet, Glycogen, Humans, Isotope Labeling, Myelin Sheath, Mass Spectrometry, Systems Analysis, Lipid Metabolism, Mice, Rats

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