Butyric acid is metabolized by various human XM-ligases (ACSM1, ACSM2B, ASCM3, ACSM4, ACSM5, and ACSM6), also known as butyrate–CoA ligase. The metabolite produced by this reaction is butyryl–CoA, and is produced as follows:
:Adenosine triphosphate + butyric acid + coenzyme A → adenosine monophosphate + pyrophosphate + butyryl-CoA
As a short-chain fatty acid, butyrate is metabolized by mitochondria as an energy (i.e., adenosine triphosphate or ATP) source through fatty acid metabolism. In particular, it is an important energy source for cells lining the mammalian colon (colonocytes). Without butyrates, colon cells undergo autophagy (i.e., self-digestion) and die.
In humans, the butyrate precursor tributyrin, which is naturally present in butter, is metabolized by triacylglycerol lipase into dibutyrin and butyrate through the reaction:
:Tributyrin +  dibutyrin + butyric acid