Coordinated Expression of Valine Catabolic Enzymes During Adipogenesis

Analysis of Activity, mRNA, Protein Levels, and Metabolic Consequences

N. Y. Kedishvili, K. M. Popov, J. A. Jaskiewicz, Robert Harris

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

3T3-L1 fibroblasts have limited enzymatic capacity to oxidize valine. Enzymes expressed in these cells allow efficient oxidation of only the first carbon of this branched chain amino acid. The pathway is effectively truncated at the level of 3-hydroxyisobutyrate because of very low expression of two enzymes required for the complete pathway, 3-hydroxyisobutyrate dehydrogenase and methylmalonate semialdehyde dehydrogenase. These two enzymes, as well as the branched chain α-ketoacid dehydrogenase, are markedly induced upon differentiation of 3T3-L1 fibroblasts into adipocytes. Flux through the first two decarboxylation steps of valine catabolism is increased dramatically after differentiation, particularly through the step catalyzed by methylmalonate semialdehyde dehydrogenase. Activation of the distal portion of the valine catabolic pathway correlates with significant increases in enzyme protein and mRNA levels for 3-hydroxyisobutyrate dehydrogenase and methylmalonate semialdehyde dehydrogenase, and this establishes the pathway in 3T3-L1 adipocytes for utilization of valine carbon for lipogenesis. The induction profiles of 3-hydroxyisobutyrate dehydrogenase and methylmalonate semialdehyde dehydrogenase are very similar, suggesting coordinate regulation of the expression of these two valine pathway-specific enzymes. induction of valine catabolism in 3T3-L1 cells is solely differentiation dependent, suggesting regulation by the same factors that govern differentiation of 3T3-L1 fibroblasts into adipocytes.

Original languageEnglish
Pages (from-to)317-322
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume315
Issue number2
DOIs
StatePublished - Dec 1994

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Adipogenesis
3-hydroxyisobutyrate dehydrogenase
Valine
Messenger RNA
Oxidoreductases
Enzymes
Fibroblasts
Adipocytes
Proteins
Carbon
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
3T3-L1 Cells
Branched Chain Amino Acids
Lipogenesis
Decarboxylation
Chemical activation
Fluxes
Oxidation

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry

Cite this

Coordinated Expression of Valine Catabolic Enzymes During Adipogenesis : Analysis of Activity, mRNA, Protein Levels, and Metabolic Consequences. / Kedishvili, N. Y.; Popov, K. M.; Jaskiewicz, J. A.; Harris, Robert.

In: Archives of Biochemistry and Biophysics, Vol. 315, No. 2, 12.1994, p. 317-322.

Research output: Contribution to journalArticle

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