Néoglucogénèse : le cours complet en 10 min (L1 · Médecine · Diététique)

Summary

The video explains gluconeogenesis, the pathway that produces glucose from non-carbohydrate precursors, especially during fasting. It is presented as a companion to glycolysis: most steps are reversible and use the same enzymes, but three irreversible glycolysis steps must be bypassed.

Where and when it occurs

Gluconeogenesis takes place mainly in the liver (the presenter estimates about 90%), and to a lesser extent in the kidneys and intestines.

During fasting, falling blood glucose prompts pancreatic alpha cells to release glucagon. Glucagon supports glucose release through both glycogen breakdown (glycogenolysis) and gluconeogenesis.

Precursors

Lactate, pyruvate, amino acids, and Krebs-cycle intermediates can feed into the pathway, converging on oxaloacetate.

Leucine and lysine are identified as non-glucogenic amino acids: they yield acetyl-CoA rather than a precursor for glucose production. Fatty acids do not directly provide carbon for gluconeogenesis in the account given, but their breakdown supplies ATP to help power the pathway.

The three bypasses of glycolysis

Because three glycolysis reactions are irreversible, gluconeogenesis uses different enzymes to bypass them:

1. Glucose-6-phosphate → glucose

   • Glycolysis uses hexokinase in the opposite direction.
   • Gluconeogenesis uses glucose-6-phosphatase, which removes a phosphate by hydrolysis.

2. Fructose-1,6-bisphosphate → fructose-6-phosphate

   • This bypasses the phosphofructokinase-1 (PFK-1) step.
   • Fructose-1,6-bisphosphatase carries out the hydrolysis.

3. Pyruvate → phosphoenolpyruvate (PEP)

   • This bypasses the pyruvate kinase step in two reactions:
     • Pyruvate carboxylase converts pyruvate to oxaloacetate, using ATP and biotin to handle CO₂.
     • PEP carboxykinase (PEPCK) converts oxaloacetate to PEP, using GTP and releasing CO₂.
   • The presenter explains that the energetically favorable decarboxylation helps drive PEP formation.

The other shared reactions are reversible and use the same enzymes in glycolysis and gluconeogenesis.

Oxaloacetate and transport

Oxaloacetate is both a gluconeogenesis intermediate and a Krebs-cycle intermediate. The presenter describes acetyl-CoA as activating pyruvate carboxylase, helping increase oxaloacetate formation when appropriate.

Pyruvate-to-oxaloacetate conversion occurs in the mitochondria, while much of the subsequent pathway occurs in the cytosol. A shuttle is mentioned for moving the relevant intermediates between compartments, but its details are not covered.

Regulation

Glycolysis and gluconeogenesis are regulated so that they do not run strongly in opposite directions at the same time.

• Fructose-2,6-bisphosphate activates PFK-1, favoring glycolysis, and inhibits fructose-1,6-bisphosphatase, opposing gluconeogenesis.
• Alanine is described as inhibiting pyruvate kinase, a glycolysis enzyme.
• The subtitles give conflicting statements about acetyl-CoA and pyruvate carboxylase: earlier they say acetyl-CoA activates it, while later they say it inhibits it. The video’s earlier explanation is consistent with its stated role in stimulating oxaloacetate formation.

Main takeaways

• Gluconeogenesis makes glucose from lactate, pyruvate, and glucogenic amino acids, mainly in the liver.
• It largely reverses glycolysis but bypasses its three irreversible steps using four enzymes: pyruvate carboxylase, PEPCK, fructose-1,6-bisphosphatase, and glucose-6-phosphatase.
• Fasting and glucagon promote glucose production, while pathway regulation coordinates gluconeogenesis with glycolysis.

Speakers and sources featured

• Pavelina, the presenter, introduces herself as having a PhD in structural biology and an interest in protein biochemistry.
• Biochimie Facile, the channel hosting the lesson.
• The presenter refers generally to earlier videos on glucose storage and related metabolism. No other speaker is identified in the subtitles.