Title:Oxaloacetate Mediates Mitochondrial Metabolism and Function
VOLUME: 7 ISSUE: 1
Author(s):Liping Yu* and William I. Sivitz*
Affiliation:CCOM NMR Core Facility, University of Iowa, Iowa City, IA, 52242, Department of Internal Medicine/Endocrinology and Metabolism, University of Iowa and the Iowa City Veterans Affairs Medical Center, Iowa City, IA, 52242
Keywords:Oxaloacetic acid, oxaloacetate, NMR, mitochondrial metabolism, mitochondria, bioenergetics,
respiration.
Abstract:Oxaloacetate, an intermediate in the tricarboxylic acid cycle, plays important roles
in regulating mitochondrial function, gluconeogenesis, the urea cycle, and amino acid syntheses.
Because this compound is not stable, more information is needed about its stability
profile before its medicinal potential can be realized. In this short review, we present current
knowledge and understanding of oxaloacetate with a focus on its stability, degradation, quantification
methods, regulation of mitochondrial function, and potential therapeutic benefits.
Further, we report previously unpublished spectral data related to the stability profile of oxaloacetate.
We found that oxaloacetate has a half-life of about 14 hours in biological aqueous
solution at 25°C before degrading into pyruvate. This mandates careful attention to handling
this compound including storage at -20 to -80°C when not in use to prolong its shelf-life.
Also, the oxaloacetate stability profile needs to be taken into account when conducting experiments
involving the compound either in clinical trials or evaluating it as a health supplement
or for other experiments. Measuring oxaloacetate by mass-spectrometry requires cumbersome
derivatization to assure stability. However, we found that NMR can be used to detect
oxaloacetate quantitatively without the need for making derivatives, and the NMR
method is sensitive enough to detect oxaloacetate in the micromolar range. Using this
method, we showed that oxaloacetate regulates mitochondrial complex II-driven respiration
by potent inhibition of succinate dehydrogenase. Moreover, a growing literature in the past
few years suggests that oxaloacetate may have therapeutic benefits in treating a variety of
diseases.
