Propionate, produced by microorganisms such as Megasphaera, Veillonella and Selenomonas species is of great importance to the host ruminant as a gluconeogenic substrate; it is a major source of glucose. Glucose is utilised as the sole energy source in erythrocytes and it is the preferred substrate for ATP synthesis in some other cell types such as neurons.

In the scheme shown below a summary of the first few reactions of propionate utilization are displayed.  They prepare the propionate to enter the TCA cycle in order to produce oxaloacetate which can then be used to produce glucose via gluconeogenisis.

After absorption across the rumen wall, propionate is transported to the liver where the enzyme Thiokinase catalyses its reaction with Coenzyme A to yield propionyl CoA.

This is then carboxylated in a reaction catalysed by Propionyl-CoA Carboxylase. This carboxylation occurs at C2 of Propionyl CoA and so the product is MethylMalonyl-CoA.

Methylmalonyl-CoA then undergoes a rearrangement in a reaction catalysed by the enzyme MethylMalonyl-CoA mutase. This enzymic activity requires vitamin B12.

Succinyl-CoA is a component of the TCA cycle and is converted to oxaloacetate and then into glucose by gluconeogenesis.

The diagram below summarizes this pathway for the utilisation of propionate.