Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 323 ( Pt 1) (Pt 1), 1-12

Role of Long-Chain Fatty acyl-CoA Esters in the Regulation of Metabolism and in Cell Signalling

Affiliations
Review

Role of Long-Chain Fatty acyl-CoA Esters in the Regulation of Metabolism and in Cell Signalling

N J Faergeman et al. Biochem J.

Abstract

The intracellular concentration of free unbound acyl-CoA esters is tightly controlled by feedback inhibition of the acyl-CoA synthetase and is buffered by specific acyl-CoA binding proteins. Excessive increases in the concentration are expected to be prevented by conversion into acylcarnitines or by hydrolysis by acyl-CoA hydrolases. Under normal physiological conditions the free cytosolic concentration of acyl-CoA esters will be in the low nanomolar range, and it is unlikely to exceed 200 nM under the most extreme conditions. The fact that acetyl-CoA carboxylase is active during fatty acid synthesis (Ki for acyl-CoA is 5 nM) indicates strongly that the free cytosolic acyl-CoA concentration is below 5 nM under these conditions. Only a limited number of the reported experiments on the effects of acyl-CoA on cellular functions and enzymes have been carried out at low physiological concentrations in the presence of the appropriate acyl-CoA-buffering binding proteins. Re-evaluation of many of the reported effects is therefore urgently required. However, the observations that the ryanodine-senstitive Ca2+-release channel is regulated by long-chain acyl-CoA esters in the presence of a molar excess of acyl-CoA binding protein and that acetyl-CoA carboxylase, the AMP kinase kinase and the Escherichia coli transcription factor FadR are affected by low nanomolar concentrations of acyl-CoA indicate that long-chain acyl-CoA esters can act as regulatory molecules in vivo. This view is further supported by the observation that fatty acids do not repress expression of acetyl-CoA carboxylase or Delta9-desaturase in yeast deficient in acyl-CoA synthetase.

Similar articles

See all similar articles

Cited by 164 PubMed Central articles

See all "Cited by" articles

References

    1. Eur J Biochem. 1978 Aug 15;89(1):33-41 - PubMed
    1. J Biol Chem. 1979 Feb 25;254(4):1248-51 - PubMed
    1. Gastroenterology. 1979 Aug;77(2):241-9 - PubMed
    1. Eur J Biochem. 1979 May 15;96(2):393-401 - PubMed
    1. FEBS Lett. 1979 Jun 15;102(2):223-6 - PubMed

MeSH terms

LinkOut - more resources

Feedback