Gluconeogenesis

Summary

The video explains gluconeogenesis, the synthesis of glucose from non-carbohydrate precursors. It focuses on producing glucose from pyruvate and compares the pathway with glycolysis.

Purpose and location

Gluconeogenesis occurs mainly in the liver and also in the kidneys. It helps maintain blood glucose levels when they are low. Glucose is especially important as a fuel for the brain and as an energy source for red blood cells.

Many reactions are shared with glycolysis and can run in either direction. However, three glycolysis reactions are strongly irreversible. Gluconeogenesis bypasses these reactions using different enzymes, so it does not simply reverse glycolysis. The pathway has 11 steps, compared with glycolysis’s 10.

Key pathway concepts

A committed step is an irreversible reaction after which a molecule is largely directed into a particular pathway. The video contrasts glycolysis’s early hexokinase reaction—with glucose-6-phosphate, a product that can enter other pathways—with the later, more committed step catalyzed by phosphofructokinase.

The reversible reactions between the irreversible steps can run in the opposite direction during gluconeogenesis. The pathway avoids futile cycling by not relying on the same enzymes to run the opposing irreversible glycolysis reactions backward.

The three bypasses

1. Pyruvate to phosphoenolpyruvate (PEP): a two-reaction bypass

   • Pyruvate enters the mitochondrion and is converted to oxaloacetate by pyruvate carboxylase.
   • This reaction uses bicarbonate, ATP, and the coenzyme biotin. Biotin is attached to a lysine in the enzyme and acts as a movable arm, carrying carbon dioxide between parts of the active site.
   • Oxaloacetate is then converted to PEP. Carbon dioxide is released, and GTP supplies the phosphate and energy needed for the reaction.
   • Oxaloacetate is also used in the citric acid cycle.

2. Fructose-1,6-bisphosphate to fructose-6-phosphate This bypasses an irreversible glycolysis step by removing a phosphate group.

3. Glucose-6-phosphate to glucose This bypasses another irreversible glycolysis step, also by removing a phosphate group.

The video describes the latter two bypasses as single-step alternatives to the corresponding glycolysis reactions.

Moving oxaloacetate and maintaining redox balance

Oxaloacetate is made in the mitochondrial matrix, but the video says it cannot be transported directly back to the cytosol. Instead, it is reduced to malate, which can cross the membrane. In the cytosol, malate is oxidized back to oxaloacetate, transferring electrons to NAD⁺ and regenerating NADH.

NADH is needed for gluconeogenesis. This transport-and-conversion route moves reducing power from the mitochondrion into the cytosol.

Energetics and endpoint

Gluconeogenesis must bypass the strongly one-way glycolysis reactions to be energetically feasible. The video states that the pathway is spontaneous overall under the conditions it discusses.

The video ends by raising the question of how the body regulates whether glycolysis or gluconeogenesis proceeds; the answer is not included in the subtitles.

Speakers and sources

• Speaker: One narrator or presenter explains the pathway.
• Other speakers or external sources: None identified in the subtitles.