Acyl-CoA thioesterase 6 is a
protein that in humans is encoded by the ACOT6gene.[5] The protein, also known as C14orf42, is an enzyme with
thioesterase activity.[5]
Function
The protein encoded by the ACOT1 gene is part of a family of
Acyl-CoAthioesterases, which catalyze the
hydrolysis of various
Coenzyme A esters of various molecules to the free acid plus CoA. These enzymes have also been referred to in the literature as acyl-CoA hydrolases, acyl-CoA thioester hydrolases, and palmitoyl-CoA hydrolases. The reaction carried out by these
enzymes is as follows:
CoA ester + H2O → free acid + coenzyme A
These enzymes use the same
substrates as long-chain acyl-CoA synthetases, but have a unique purpose in that they generate the free acid and CoA, as opposed to long-chain acyl-CoA synthetases, which ligate fatty acids to CoA, to produce the CoA ester.[6] The role of the ACOT- family of enzymes is not well understood; however, it has been suggested that they play a crucial role in regulating the intracellular levels of CoA esters, Coenzyme A, and free fatty acids. Recent studies have shown that Acyl-CoA esters have many more functions than simply an energy source. These functions include
allosteric regulation of enzymes such as
acetyl-CoA carboxylase,[7]hexokinase IV,[8] and the citrate condensing enzyme. Long-chain acyl-CoAs also regulate opening of
ATP-sensitive potassium channels and activation of
Calcium ATPases, thereby regulating
insulin secretion.[9] A number of other cellular events are also mediated via acyl-CoAs, for example signal transduction through
protein kinase C, inhibition of
retinoic acid-induced apoptosis, and involvement in budding and fusion of the
endomembrane system.[10][11][12] Acyl-CoAs also mediate protein targeting to various membranes and regulation of
G Protein α subunits, because they are substrates for protein acylation.[13] In the
mitochondria, acyl-CoA esters are involved in the acylation of mitochondrial NAD+ dependent
dehydrogenases; because these enzymes are responsible for
amino acid catabolism, this acylation renders the whole process inactive. This mechanism may provide metabolic crosstalk and act to regulate the
NADH/NAD+ ratio in order to maintain optimal mitochondrial
beta oxidation of fatty acids.[14] The role of CoA esters in
lipid metabolism and numerous other intracellular processes are well defined, and thus it is hypothesized that ACOT- enzymes play a role in modulating the processes these metabolites are involved in.[15]
^Ogiwara H, Tanabe T, Nikawa J, Numa S (Aug 1978). "Inhibition of rat-liver acetyl-coenzyme-A carboxylase by palmitoyl-coenzyme A. Formation of equimolar enzyme-inhibitor complex". European Journal of Biochemistry. 89 (1): 33–41.
doi:
10.1111/j.1432-1033.1978.tb20893.x.
PMID29756.
^Srere PA (Dec 1965). "Palmityl-coenzyme A inhibition of the citrate-condensing enzyme". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 106 (3): 445–55.
doi:
10.1016/0005-2760(65)90061-5.
PMID5881327.
^Hunt MC, Alexson SE (Mar 2002). "The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism". Progress in Lipid Research. 41 (2): 99–130.
doi:
10.1016/s0163-7827(01)00017-0.
PMID11755680.
Acyl-CoA thioesterase 6 is a
protein that in humans is encoded by the ACOT6gene.[5] The protein, also known as C14orf42, is an enzyme with
thioesterase activity.[5]
Function
The protein encoded by the ACOT1 gene is part of a family of
Acyl-CoAthioesterases, which catalyze the
hydrolysis of various
Coenzyme A esters of various molecules to the free acid plus CoA. These enzymes have also been referred to in the literature as acyl-CoA hydrolases, acyl-CoA thioester hydrolases, and palmitoyl-CoA hydrolases. The reaction carried out by these
enzymes is as follows:
CoA ester + H2O → free acid + coenzyme A
These enzymes use the same
substrates as long-chain acyl-CoA synthetases, but have a unique purpose in that they generate the free acid and CoA, as opposed to long-chain acyl-CoA synthetases, which ligate fatty acids to CoA, to produce the CoA ester.[6] The role of the ACOT- family of enzymes is not well understood; however, it has been suggested that they play a crucial role in regulating the intracellular levels of CoA esters, Coenzyme A, and free fatty acids. Recent studies have shown that Acyl-CoA esters have many more functions than simply an energy source. These functions include
allosteric regulation of enzymes such as
acetyl-CoA carboxylase,[7]hexokinase IV,[8] and the citrate condensing enzyme. Long-chain acyl-CoAs also regulate opening of
ATP-sensitive potassium channels and activation of
Calcium ATPases, thereby regulating
insulin secretion.[9] A number of other cellular events are also mediated via acyl-CoAs, for example signal transduction through
protein kinase C, inhibition of
retinoic acid-induced apoptosis, and involvement in budding and fusion of the
endomembrane system.[10][11][12] Acyl-CoAs also mediate protein targeting to various membranes and regulation of
G Protein α subunits, because they are substrates for protein acylation.[13] In the
mitochondria, acyl-CoA esters are involved in the acylation of mitochondrial NAD+ dependent
dehydrogenases; because these enzymes are responsible for
amino acid catabolism, this acylation renders the whole process inactive. This mechanism may provide metabolic crosstalk and act to regulate the
NADH/NAD+ ratio in order to maintain optimal mitochondrial
beta oxidation of fatty acids.[14] The role of CoA esters in
lipid metabolism and numerous other intracellular processes are well defined, and thus it is hypothesized that ACOT- enzymes play a role in modulating the processes these metabolites are involved in.[15]
^Ogiwara H, Tanabe T, Nikawa J, Numa S (Aug 1978). "Inhibition of rat-liver acetyl-coenzyme-A carboxylase by palmitoyl-coenzyme A. Formation of equimolar enzyme-inhibitor complex". European Journal of Biochemistry. 89 (1): 33–41.
doi:
10.1111/j.1432-1033.1978.tb20893.x.
PMID29756.
^Srere PA (Dec 1965). "Palmityl-coenzyme A inhibition of the citrate-condensing enzyme". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 106 (3): 445–55.
doi:
10.1016/0005-2760(65)90061-5.
PMID5881327.
^Hunt MC, Alexson SE (Mar 2002). "The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism". Progress in Lipid Research. 41 (2): 99–130.
doi:
10.1016/s0163-7827(01)00017-0.
PMID11755680.