Pyruvic acid | EPFL Graph Search

Pyruvic acid (IUPAC name: 2-oxopropanoic acid, also called acetoic acid) (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell. Pyruvic acid can be made from glucose through glycolysis, converted back to carbohydrates (such as glucose) via gluconeogenesis, or converted to fatty acids through a reaction with acetyl-CoA. It can also be used to construct the amino acid alanine and can be converted into ethanol or lactic acid via fermentation. Pyruvic acid supplies energy to cells through the citric acid cycle (also known as the Krebs cycle) when oxygen is present (aerobic respiration), and alternatively ferments to produce lactate when oxygen is lacking. Chemistry In 1834, Théophile-Jules Pelouze distilled tartaric acid and isolated glutaric acid and another unknown organic acid. Jöns Jacob Berzelius characterized th

Performance and reproducibility of C-13 and N-15 hyperpolarization using a cryogen-free DNP polarizer

Arianna Ferrari, Hikari Ananda Infinity Yoshihara

The setup, operational procedures and performance of a cryogen-free device for producing hyperpolarized contrast agents using dissolution dynamic nuclear polarization (dDNP) in a preclinical imaging center is described. The polarization was optimized using the solid-state, DNP-enhanced NMR signal to calibrate the sample position, microwave and NMR frequency and power and flip angle. The polarization of a standard formulation to yield similar to 4 mL, 60 mM 1-C-13-pyruvic acid in an aqueous solution was quantified in five experiments to P(C-13) = (38 +/- 6) % (19 +/- 1) s after dissolution. The mono-exponential time constant of the build-up of the solid-state polarization was quantified to (1032 +/- 22) s. We achieved a duty cycle of 1.5 h that includes sample loading, monitoring the polarization build-up, dissolution and preparation for the next run. After injection of the contrast agent in vivo, pyruvate, pyruvate hydrate, lactate, and alanine were observed, by measuring metabolite maps. Based on this work sequence, hyperpolarized N-15 urea was obtained (P(N-15) = (5.6 +/- 0.8) % (30 +/- 3) s after dissolution).

NATURE PORTFOLIO2022

Radical-free hyperpolarized MRI using endogenously occurring pyruvate analogues and UV-induced nonpersistent radicals

Lionel Pierre Arn, Josefina Adriana Maria Bastiaansen, Andrea Capozzi, Rolf Gruetter, Alice Radaelli, Hikari Ananda Infinity Yoshihara, Claudia Christina Zanella

It was recently demonstrated that nonpersistent radicals can be generated in frozen solutions of metabolites such as pyruvate by irradiation with UV light, enabling radical-free dissolution dynamic nuclear polarization. Although pyruvate is endogenous, the presence of pyruvate may interfere with metabolic processes or the detection of pyruvate as a metabolic product, making it potentially unsuitable as a polarizing agent. Therefore, the aim of the current study was to characterize solutions containing endogenously occurring alternatives to pyruvate as UV-induced nonpersistent radical precursors for in vivo hyperpolarized MRI. The metabolites alpha-ketovalerate (alpha kV) and alpha-ketobutyrate (alpha kB) are analogues of pyruvate and were chosen as potential radical precursors. Sample formulations containing alpha kV and alpha kB were studied with UV-visible spectroscopy, irradiated with UV light, and their nonpersistent radical yields were quantified with electron spin resonance and compared with pyruvate. The addition of C-13-labeled substrates to the sample matrix altered the radical yield of the precursors. Using alpha kB increased the C-13-labeled glucose liquid-state polarization to 16.3% +/- 1.3% compared with 13.3% +/- 1.5% obtained with pyruvate, and 8.9% +/- 2.1% with alpha kV. For [1-C-13]butyric acid, polarization levels of 12.1% +/- 1.1% for alpha kV, 12.9% +/- 1.7% for alpha kB, 1.5% +/- 0.2% for OX063 and 18.7% +/- 0.7% for Finland trityl, were achieved. Hyperpolarized [1-C-13]butyrate metabolism in the heart revealed label incorporation into [1-C-13]acetylcarnitine, [1-C-13]acetoacetate, [1-C-13]butyrylcarnitine, [5-C-13]glutamate and [5-C-13]citrate. This study demonstrates the potential of alpha kV and alpha kB as endogenous polarizing agents for in vivo radical-free hyperpolarized MRI. UV-induced, nonpersistent radicals generated in endogenous metabolites enable high polarization without requiring radical filtration, thus simplifying the quality-control tests in clinical applications.

WILEY2021

High-field dissolution dynamic nuclear polarization of [1-C-13]pyruvic acid

Emine Can, Arnaud Comment, Hikari Ananda Infinity Yoshihara

[1-C-13]pyruvate is the most widely used hyperpolarized metabolic magnetic resonance imaging agent. Using a custom-built 7.0 T polarizer operating at 1.0 K and trityl radical-doped [1-C-13] pyruvic acid, unextrapolated solution-state C-13 polarization greater than 60% was measured after dissolution and rapid transfer to a spectrometer magnet, demonstrating the signal enhancement attainable using optimized hardware. Slower rates of polarization under these conditions can be largely overcome with higher radical concentrations.

Royal Soc Chemistry2016

Radical-free hyperpolarized MRI using endogenously occurring pyruvate analogues and UV-induced nonpersistent radicals

Lionel Pierre Arn, Josefina Adriana Maria Bastiaansen, Andrea Capozzi, Rolf Gruetter, Alice Radaelli, Hikari Ananda Infinity Yoshihara, Claudia Christina Zanella

WILEY2021