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Comment
. 2015 Feb;21(2):108-9.
doi: 10.1038/nm.3789.

Limitations of detection of anaplerosis and pyruvate cycling from metabolism of [1-(13)C] acetate

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Comment

Limitations of detection of anaplerosis and pyruvate cycling from metabolism of [1-(13)C] acetate

Shawn C Burgess et al. Nat Med. 2015 Feb.
No abstract available

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Figures

Figure 1
Figure 1
The effect of pyruvate cycling on the steady-state 13C1/13C5 of glutamate. Data was simulated using program tcaSIM (see source data). All simulations were conducted using an [1-13C]acetyl-CoA fractional enrichment of 0.22 and 13CO2 fractional enrichment of 0.06 as reported by Befroy et al. Anaplerosis relative to TCA cycle flux (CS) was varied from 1.4, as reported by Befroy et al., to 8. The 13C1/13C5 ratio decreases by 40% across this range under the assumption of no pyruvate cycling (e.g. PK) activity. The 13C1/13C5 ratio is unresponsive to anaplerosis when pyruvate cycling is concomitantly active because the resulting 13C pyruvate condenses with 13CO2 (i.e. PC) and ultimately re-generates [1-13C]glutamate. Most notably, the 13C1/13C5 method used by Befroy et al. cannot distinguish low anaplerosis from higher values criticized by Befroy et al.

Comment in

  • Response to burgess.
    Befroy DE, Kibbey RG, Perry RJ, Petersen KF, Rothman DL, Shulman GI. Befroy DE, et al. Nat Med. 2015 Feb;21(2):109-10. doi: 10.1038/nm.3790. Nat Med. 2015. PMID: 25654597 Free PMC article. No abstract available.

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