Activated fatty acids
Fatty acyl-CoA feedback inhibition
Also searched as Fatty acyl-CoA feedback inhibition.
You want it cleared, because this is the most elegant trap in the pathway. Released fat is immediately activated into this form for burning or storage. But in this form it binds the activator the main lipase needs, blocks the second lipase, and feeds the pathway that makes the lipid which switches on the enzyme that erases the activating marks. The product of the reaction disables the reaction, by three routes. The only way out is to burn it or carry it away.
In depth
What released fat becomes inside the cell — and the form in which it switches its own release off.
What drives it
Releases stored fat increases it.
'lipolysis derived FFAs need to be activated to metabolizable lc-CoAs via the long-chain acyl coenzyme A synthetase for further metabolization such as beta-oxidation, synthesis of complex lipids, or protein acylation' (doi 10.3389/fphys.2022.826314). ⇒ the fat you release becomes the molecule that stops further release, unless burned or carried away. doi 10.3389/fphys.2022.826314
Fatty acid activation increases it.
The enzyme that sets the trap it also needs. 'lipolysis derived FFAs need to be activated to metabolizable lc-CoAs via the long-chain acyl coenzyme A synthetase (ACSL) for further metabolization such as beta-oxidation, synthesis of complex lipids, or protein acylation' (doi 10.3389/fphys.2022.826314). ⇒ NO disposal without this step, and NO self-inhibition without it either. doi 10.3389/fphys.2022.826314
What it drives
It reduces Lipase activator.
The product disables the reaction. 'lc-CoA acts as an endogenous allosteric regulator of lipid droplet-associated protein ABHD5/CGI58, an essential co-activator of PNPLA2/ATGL... Upon binding to CGI58, LC-CoA rapidly modulates the interaction of CGI58 with perilipin proteins, thereby preventing its binding to ATGL and the activation of ATGL'. doi 10.3389/fphys.2022.826314
It reduces Fat-releasing enzyme (HSL).
'LC-CoAs, most notably OLEOYL-CoA, inhibit HSL and ATGL activity by non-competitive inhibition' (doi 10.3389/fphys.2022.826314). Conditional: 'the inhibitory effect of LC-CoA on HSL activity is dependent on the phosphorylation state of HSL and further enhanced by interactions with acyl-CoA-binding protein.'. doi 10.3389/fphys.2022.826314
It increases Ceramide load.
'Acyl-CoAs can further enter the ceramide-biosynthesis pathway. Ceramides limit lipolysis by activating the PP2A-dependent dephosphorylation of HSL' (doi 10.3389/fphys.2022.826314). A third route from the same product to the same off-switch, and a mechanistic bridge to the Ceramide Blocker blend. doi 10.3389/fphys.2022.826314
It increases Ceramide synthase.
Long-chain acyl-CoA is the obligate acyl-donor co-substrate for ceramide synthase. PMC12132366
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.