Gluconeogenesis

Summary

Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys. It is one of two primary mechanisms – the other being degradation of glycogen (glycogenolysis) – used by humans and many other animals to maintain blood sugar levels, avoiding low levels (hypoglycemia). In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise. In humans, substrates for gluconeogenesis may come from any non-carbohydrate sources that can be converted to pyruvate or in

Official source

https://en.wikipedia.org/wiki/Gluconeogenesis

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Role of Bicaudal C1 in renal gluconeogenesis and its novel interaction with the CTLH complex

Daniel Constam, Simon Fortier, Manuela Isenschmid, Lucía Carolina Leal Esteban, Benjamin Marcel Daniel Rothé

2018

Aspartic acid is involved in several central metabolic pathways, including gluconeogenesis, the urea cycle, de novo nucleotide synthesis, the malate-aspartate shuttle, and via transmination the TCA cycle. The conversion in vivo of hyperpolarized [1-13C]pyruvate to aspartate, via pyruvate carboxylation to oxaloacetate, has been reported in rat kidney [1] and in the mouse liver [2]. Additionally, the metabolism of hyperpolarized [1-13C]aspartate to oxaloacetate has been noted in cultured cells supplemented with 2-oxoglutarate [3]. Aspartate is also of interest with its conversion to succinate in ischemic tissue implicated in subsequent reperfusion injury [4]. Here we report initial experiments with hyperpolarized [1-13C]aspartate in the rat kidney. [1-13C]Aspartic acid was formulated with OX063 trityl radical as in [3] as the tris salt, with the addition of glycerol (14% v/v) to improve glassing. The formulation is highly viscous and dissolves poorly, limiting the usable dose. Experiments were performed in a 9.4T animal scanner and a 7T polarizer operating at 1K, with automated rapid transfer and infusion. Rats (n=2) were isoflurane anesthesized, a femoral vein catheterized, and a quadrature 13C surface coil placed over the kidney. Respiration-triggered (TR ~3s) pulse-acquire (BIR4-30o) scans were started at the time of infusion of [1-13C]aspartate (~16 μmol/kg in 1.2 ml). Three metabolites were detected, with chemical shifts of 183.51 ppm (1.5%), 182.31 ppm (0.5%) and 181.26 ppm (0.6%), corresponding to [1-13C]malate, [4-13C]malate and an unidentified species provisionally assigned as N-acetyl[1-13C]aspartate. [4- 13C]aspartate was at natural abundance, but [4-13C]malate results from conversion to fumarate or succinate and label scrambling, and the greater prominence of [1-13C]malate indicates oxaloacetate as an intermediate. These results show the potential of hyperpolarized [1- 13C]aspartate as an in vivo metabolic probe.

2018

Assessment of Aspartate and Bicarbonate Produced From Hyperpolarized [1-13C]Pyruvate as Markers of Renal Gluconeogenesis

Arnaud Comment, Hikari Ananda Infinity Yoshihara

As both a consumer and producer of glucose, the kidney plays a significant role in glucose homeostasis. Measuring renal gluconeogenesis requires invasive techniques, and less invasive methods would allow renal gluconeogenesis to be measured more routinely. Magnetic resonance spectroscopy and imaging of infused substrates bearing hyperpolarized carbon-13 spin labels allows metabolism to be detected within the body with excellent sensitivity. Conversion of hyperpolarized 1-13C pyruvate in the fasted rat liver is associated with gluconeogenic flux through phosphoenolpyruvate carboxykinase (PEPCK) rather than pyruvate dehydrogenase (PDH), and this study tested whether this was also the case in the kidney. The left kidney was scanned in fed and overnight-fasted rats either with or without prior treatment by the PEPCK inhibitor 3- mercaptopicolinic acid (3-MPA) following infusion of hyperpolarized 1-13C pyruvate. The 13C-bicarbonate signal normalized to the total metabolite signal was 3.2-fold lower in fasted rats (p = 0.00073) and was not significantly affected by 3-MPA treatment in either nutritional state. By contrast, the normalized [1-13C]aspartate signal was on average 2.2-fold higher in the fasted state (p = 0.038), and following 3-MPA treatment it was 2.8-fold lower in fed rats and 15-fold lower in fasted rats (p = 0.001). These results confirm that, unlike in the liver, most of the pyruvate-to-bicarbonate conversion in the fasted kidney results from PDH flux. The higher conversion to aspartate in fasted kidney and the marked drop following PEPCK inhibition demonstrate the potential of this metabolite as a marker of renal gluconeogenesis.

2021