Gluconeogenesis from ascorbic acid: ascorbate recycling in isolated murine hepatocytes

Area of Science:

• Biochemistry
• Cell Biology
• Metabolic Pathways

Background:

• Ascorbic acid (vitamin C) plays crucial roles in cellular metabolism.
• Understanding the regulation of its synthesis and breakdown is vital for metabolic research.
• Previous studies have not fully elucidated the interplay between ascorbate metabolism and glucose production.

Purpose of the Study:

• To investigate the synthesis and breakdown of ascorbic acid in isolated mouse hepatocytes.
• To explore the relationship between ascorbate metabolism and glucose production.
• To identify novel pathways involved in ascorbate recycling.

Main Methods:

• Isolated hepatocytes from fasted mice were used.
• Stimulation of gluconeogenesis using alanine or xylitol.
• Addition of ascorbate or dehydroascorbate to cell cultures.
• Measurement of glucose production and pentose phosphate pathway intermediates.
• Inhibition of specific metabolic pathways.

Main Results:

• Gluconeogenesis stimulation led to ascorbate synthesis.
• Ascorbate or dehydroascorbate addition increased glucose production and xylulose 5-phosphate levels.
• Stimulating ascorbate oxidation or inhibiting dehydroascorbate reduction enhanced glucose formation.
• Pentose phosphate pathway inhibition reduced dehydroascorbate-driven glucose production and increased xylulose 5-phosphate accumulation.

Conclusions:

• Ascorbate can be recycled through a novel pathway.
• This pathway involves intermediates from the pentose phosphate pathway, gluconeogenesis, and the hexuronic acid pathway.
• The findings provide new insights into the metabolic regulation of ascorbate and glucose homeostasis.