ACOT2: Difference between revisions

These enzymes use the same [[substrate (chemistry)|substrate]]s 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.<ref>{{cite journal|last1=Mashek|first1=DG|last2=Bornfeldt|first2=KE|last3=Coleman|first3=RA|last4=Berger|first4=J|last5=Bernlohr|first5=DA|last6=Black|first6=P|last7=DiRusso|first7=CC|last8=Farber|first8=SA|last9=Guo|first9=W|last10=Hashimoto|first10=N|last11=Khodiyar|first11=V|last12=Kuypers|first12=FA|last13=Maltais|first13=LJ|last14=Nebert|first14=DW|last15=Renieri|first15=A|last16=Schaffer|first16=JE|last17=Stahl|first17=A|last18=Watkins|first18=PA|last19=Vasiliou|first19=V|last20=Yamamoto|first20=TT|title=Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family.|journal=Journal of lipid research|date=October 2004|volume=45|issue=10|pages=1958–61|pmid=15292367|doi=10.1194/jlr.e400002-jlr200}}</ref> 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]],<ref>{{cite journal|last1=Ogiwara|first1=H|last2=Tanabe|first2=T|last3=Nikawa|first3=J|last4=Numa|first4=S|title=Inhibition of rat-liver acetyl-coenzyme-A carboxylase by palmitoyl-coenzyme A. Formation of equimolar enzyme-inhibitor complex.|journal=European journal of biochemistry / FEBS|date=15 August 1978|volume=89|issue=1|pages=33–41|pmid=29756|doi=10.1111/j.1432-1033.1978.tb20893.x}}</ref> [[hexokinase]] IV,<ref>{{cite journal|last1=Srere|first1=PA|title=Palmityl-coenzyme A inhibition of the citrate-condensing enzyme.|journal=Biochimica et Biophysica Acta|date=2 December 1965|volume=106|issue=3|pages=445–55|pmid=5881327|doi=10.1016/0005-2760(65)90061-5}}</ref> and the citrate condensing enzyme. Long-chain acyl-CoAs also regulate opening of [[ATP-sensitive potassium channel]]s and activation of [[Calcium ATPase]]s, thereby regulating [[insulin]] secretion.<ref>{{cite journal|last1=Gribble|first1=FM|last2=Proks|first2=P|last3=Corkey|first3=BE|last4=Ashcroft|first4=FM|title=Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA.|journal=The Journal of Biological Chemistry|date=9 October 1998|volume=273|issue=41|pages=26383–7|pmid=9756869|doi=10.1074/jbc.273.41.26383}}</ref> 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]].<ref>{{cite journal|last1=Nishizuka|first1=Y|title=Protein kinase C and lipid signaling for sustained cellular responses.|journal=FASEB journal : official publication of the Federation of American Societies for Experimental BiologyJournal|date=April 1995|volume=9|issue=7|pages=484–96|pmid=7737456}}</ref><ref>{{cite journal|last1=Glick|first1=BS|last2=Rothman|first2=JE|title=Possible role for fatty acyl-coenzyme A in intracellular protein transport.|journal=Nature|volume=326|issue=6110|pages=309–12|pmid=3821906|doi=10.1038/326309a0|year=1987}}</ref><ref>{{cite journal|last1=Wan|first1=YJ|last2=Cai|first2=Y|last3=Cowan|first3=C|last4=Magee|first4=TR|title=Fatty acyl-CoAs inhibit retinoic acid-induced apoptosis in Hep3B cells.|journal=Cancer letters|date=1 June 2000|volume=154|issue=1|pages=19–27|pmid=10799735|doi=10.1016/s0304-3835(00)00341-4}}</ref> Acyl-CoAs also mediate protein targeting to various membranes and regulation of [[G Protein]] α subunits, because they are substrates for protein acylation.<ref>{{cite journal|last1=Duncan|first1=JA|last2=Gilman|first2=AG|title=A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein alpha subunits and p21(RAS).|journal=The Journal of Biological Chemistry|date=19 June 1998|volume=273|issue=25|pages=15830–7|pmid=9624183|doi=10.1074/jbc.273.25.15830}}</ref> In the [[mitochondria]], acyl-CoA esters are involved in the acylation of mitochondrial NAD+ dependent [[dehydrogenase]]s; because these enzymes are responsible for [[Amino acid#Catabolism|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.<ref>{{cite journal|last1=Berthiaume|first1=L|last2=Deichaite|first2=I|last3=Peseckis|first3=S|last4=Resh|first4=MD|title=Regulation of enzymatic activity by active site fatty acylation. A new role for long chain fatty acid acylation of proteins.|journal=The Journal of Biological Chemistry|date=4 March 1994|volume=269|issue=9|pages=6498–505|pmid=8120000}}</ref> 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.<ref>{{cite journal|last1=Hunt|first1=MC|last2=Alexson|first2=SE|title=The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism.|journal=Progress in Lipid Research|date=March 2002|volume=41|issue=2|pages=99–130|pmid=11755680|doi=10.1016/s0163-7827(01)00017-0}}</ref>