Abstract
Pyruvate carboxylase (PC) is an enzyme that catalyzes pyruvate carboxylation for the formation of a tricarboxylic acid (TCA) cycle intermediate, oxaloacetate. It plays a major role in the regulation of gluconeogenesis and replenishment of the TCA cycle for biosynthesis. In particular, fasting promotes gluconeogenesis from pyruvate, increasing PC flux. PC is under complex regulation by hormones, substates, and cofactors, in response to nutrient changes. Therefore, metabolic changes associated with PC need to be understood in the context of nutritional and physiological conditions. This chapter discusses currently available methods, from conventional approaches to state-of-the-art noninvasive in vivo imaging techniques, used in human and animal models to assess PC activity, particularly in fasting condition. Quantification of PC activity through in vitro or ex vivo isotopomer analysis and monitoring PC in vivo using hyperpolarized substrates are reviewed.
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Abbreviations
- Acetyl-CoA:
-
Acetyl coenzyme A
- ALT:
-
Alanine aminotransferase
- DNP:
-
Dynamic nuclear polarization
- HP:
-
Hyperpolarized
- IV:
-
Intravenous
- LDH:
-
Lactate dehydrogenase
- LPCKO:
-
Liver-specific knockout of Pcx gene
- MS:
-
Mass spectrometry
- NAFLD:
-
Nonalcoholic fatty liver disease
- NMR:
-
Nuclear magnetic resonance
- PC:
-
Pyruvate carboxylase
- PDH:
-
Pyruvate dehydrogenase
- PEP:
-
Phosphoenolpyruvate
- PEPCK:
-
Phosphoenolpyruvate carboxykinase
- T1:
-
Spin-lattice relaxation times
- TBI:
-
Traumatic brain injury
- TCA cycle:
-
Tricarboxylic acid cycle
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Chen, J., Park, J.M. (2022). Assessing Pyruvate Carboxylase Flux as a Mechanistic Biological Marker in Fasting. In: Patel, V.B., Preedy, V.R. (eds) Biomarkers in Nutrition . Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Cham. https://doi.org/10.1007/978-3-031-07389-2_27
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