Fatty acids are carboxylic acids with a carbon aliphatic chain. The fatty acids can be divided by the length of this chain, being considered as short-chain (1–6 carbons), medium-chain (7–12 carbons) and long-chain and very long-chain fatty acids (>12 carbons). Long-chain fatty acids must be bound to carnitine to enter the mitochondrial matrix, in a reaction that can be catalysed by carnitine acyltransferase. For this reason, long-chain fatty acids, such as palmitate (16 carbons) is frequently supplied to mt-preparations in the activated form of palmitoylcarnitine. Fatty acids with shorter chains, as octanoate (8 carbons) may enter the mitochondrial matrix, however, in HRR they are more frequently supplied also in the activated form, such as octanoylcarnitine.
Once in the mitochondrial matrix, the fatty acid oxidation (FAO) occurs, generating acetyl-CoA, NADH and FADH2. In the fatty acid oxidation pathway control state electrons are fed into the F-junction involving the electron transferring flavoprotein (CETF). FAO cannot proceed without a substrate combination of fatty acids & malate, and inhibition of CI blocks FAO. Low concentration of malate, typically 0.1 mM, does not saturate the N-pathway; but saturates the F-pathway.
Reference: Gnaiger 2020 BEC MitoPathways, Schönfeld 2016 J Lipid Res
Fatty acids used in HRR
- Octanoylcarnitine (Oct)
- Palmitoylcarnitine (Pal)
- Octanoate (Oca)
MitoPedia topics: Substrate and metabolite