Fatty acid metabolism

Butyryl-CoA interconverts to and from 3-oxohexanoyl-CoA by acetyl-CoA acetyltransferase (or thiolase).^[6] In terms of organic chemistry, the reaction is the reverse of a Claisen condensation.^{[7][8][9][10][11][12]} Subsequently butyryl-CoA is converted into crotonyl-CoA. The conversion is catalyzed by electron-transfer flavoprotein 2,3-oxidoreductase.^[13] This enzyme has many synonyms that are orthologous to each other, including butyryl-CoA dehydrogenase,^[14][15][16] acyl-CoA dehydrogenase,^[17] acyl-CoA oxidase,^[18] and short-chain 2-methylacyl-CoA dehydrogenase^[19]

Fermentation

Butyryl-CoA is an intermediate of the fermentation pathway found in Clostridium kluyveri.^[20][21][22] This species can ferment acetyl-CoA and succinate into butanoate, extracting energy through the process.^[21][22] The fermentation pathway from ethanol to acetyl-CoA to butanoate is also known as ABE fermentation.

Butyryl-CoA is reduced from crotonyl-CoAcatalyzing by butyryl-CoA dehydrogenase, where two NADH molecules donate four electrons, with two of them reducing ferredoxin ([2Fe-2S] cluster) and the other two reducing crotonyl-CoA into butyryl-CoA.^[23][24][25] Subsequently, butyryl-CoA is converted into butanoate by propionyl-CoA transferase, which transfers the coenzyme-A group onto an acetate, forming acetyl-CoA.^[26][27]

It is essential in reducing ferredoxins in anaerobic bacteria and archaea so that electron transport phosphorylation and substrate-level phosphorylation can occur with increased efficiency.^[28]

4-aminobutanoate (GABA) degradation

Butyryl-CoA is also an intermediate found in 4-aminobutanoate (GABA) degradation.^[29] 4-aminobutanoate (GABA) has two fates in this degradation pathway. When discovered in Acetoanaerobium sticklandii and Pseudomonas fluorescens, 4-aminobutanoate was converted into glutamate, which can be deaminated, releasing ammonium.^[30][31][32]However, in Acetoanaerobium sticklandii and Clostridium aminobutyricum, 4-aminobutanoate was converted into succinate semialdehyde and, through a series of steps via the intermediate of butanoyl-CoA, finally converted into butanoate. ^[33][34]

The degradation pathway plays an important role in regulating the concentration of GABA, which is an inhibitory neurotransmitter that reduces neuronal excitability.^[35] Dysregulation of GABA degradation can lead to imbalances in neurotransmitter levels, contributing to various neurological disorders such as epilepsy, anxiety, and depression.^[36][37]The reaction mechanism is the same as that in the fermentation pathway, where butyryl-CoA is first reduced from crotonyl-CoA and then converted into butanoate.^[29]