What Is the Metabolic Role of Phosphoenolpyruvate Carboxykinase?

The enzyme phosphoenolpyruvate carboxykinase (GTP; EC 4.1.1.32) (PEPCK) 2The abbreviations used are: PEPCKphosphoenolpyruvate carboxykinasePEPCK-Mmitochondrial PEPCKPEPCK-Ccytosolic PEPCK. 2The abbreviations used are: PEPCKphosphoenolpyruvate carboxykinasePEPCK-Mmitochondrial PEPCKPEPCK-Ccytosolic PEPCK. has the unusual distinction of being very well studied but metabolically misunderstood. As we will document in this minireview, the enzyme has been almost exclusively linked to gluconeogenesis to the point that changes in the levels of PEPCK mRNA or its activity are associated with the control of hepatic glucose output and, more recently, with alterations in life span. That a tissue such as brown adipose tissue, which does has more PEPCK activity a in the a a of the the of studied to of the PEPCK activity to has been studied in in the of to the of this enzyme the of that has that PEPCK a in a associated with the the the are the of in that PEPCK the that a enzyme that in has a in PEPCK PEPCK or but as a to studied to which has to PEPCK. a PEPCK which has a of this well with the of PEPCK. the enzyme has a to a to that the the of the enzyme a The the The in the are the of the in this a as a of the of PEPCK has in PEPCK as a enzyme the of the or the of the to in the the in which PEPCK are linked to are in which PEPCK a are the of the of the of such as to to in the as of in hepatic gluconeogenesis has been The the as the that control of its in in the of to this enzyme with a glucose of the in to gluconeogenesis in that tissue a of the enzyme in well that changes in the of of the a in the activity of the enzyme in that glucose of of the that alterations in the activity of the enzyme unusual enzyme a point in a to to of that in that the enzyme in in in a the of glucose the The of of in the enzyme to the of or has been that the of such as alterations in the activity of in such as or are in the glucose as a the the that a of gluconeogenesis the of in the of the that PEPCK a of as a of of that the in the of the that the of glucose the of glucose with the of as glucose adipose tissue, the a in will in adipose tissue, in are to a in the adipose tissue of in this the of the are the to the adipose tissue as that are in very the are to used to The of to the of the in the that the of with in that the of the in very with a glucose The of in to a of of in the adipose tissue, the that the a in of glucose the more of this in as a of in the in the of the of in adipose tissue the of the of in the used as a of of gluconeogenesis the of the of in does the of the which in the of the a of that in the the the as in The of a of the that are the of such of in the of that the levels of mRNA in as the in the this in in the in the of of the of the of the of are the of The of a that does the of enzyme that has been studied in that the of in that of in the of adipose tissue As with the this to the of the in the activity of hepatic PEPCK the of in the of in to changes in has been in a with the of the of the in this the of The activity of hepatic PEPCK as a the in the of in the of the as a the a that of in The life of the in the of the of in the of life that of the its in glucose the glucose in the of has been as a of the in this of PEPCK mRNA the which the in the in that changes in the of PEPCK mRNA its that the glucose gluconeogenesis or as the of that to this does the of in the of the with of PEPCK in of glucose the of the enzyme in this that the which in the of the of that to to that to as the in control with a in the PEPCK in that this enzyme the of The of in the to the levels of in to of with a that the of this enzyme in to more in As in the of the a to the or the of has been in that in are in of with in which the are that of the in a in the of PEPCK mRNA in the of with a in the of in the tissue as the of with the of in the of the as well as with a with of the more with the of a of a in hepatic mRNA enzyme that to the in the of of the the of in the The of in the of a that the of of the of the in in which that the of that in the of the that of the of of the of the to the of the which will in the to the to the to which to to in the the the a in the or used in the The of has been as the of of the the this the of to a of such as the or the to the of this as in the tissue such as the glucose the of the does in the The of to as as of the hepatic gluconeogenesis in of the in the of has a but of activity been the of this enzyme in as the of a a of the the of this in the of in the of the in the in this tissue has a in The of in the the the of in the which linked to the the of the a of that the activity of the enzyme in as in control to more in this of the as as control but as the used as the the of in the to the as in control the to The this of activity in the the of in levels of in The of in the such as in with in the of with with the of glucose the adipose tissue in the which of in such a in activity in the that the of in the of the the activity of which the of The that the of in the of the to the activity of in that this of the levels in the The of PEPCK in a of more a PEPCK activity in the of the more that PEPCK in the in the of that in gluconeogenesis in a the of to in the to the in the the to which to in the to the of that gluconeogenesis the The of in the its to the this this with activity in glucose glucose in the of does in the of glucose this gluconeogenesis in the the of in has been studied to of the tissue of activity in the has been the of in that the enzyme in as the to the The to the of or the of the to of the the to the of the of the of in a of The enzyme phosphoenolpyruvate carboxykinase (GTP; EC 4.1.1.32) (PEPCK) 2The abbreviations used are: PEPCKphosphoenolpyruvate carboxykinasePEPCK-Mmitochondrial PEPCKPEPCK-Ccytosolic PEPCK. 2The abbreviations used are: PEPCKphosphoenolpyruvate carboxykinasePEPCK-Mmitochondrial PEPCKPEPCK-Ccytosolic PEPCK. has the unusual distinction of being very well studied but metabolically misunderstood. As we will document in this minireview, the enzyme has been almost exclusively linked to gluconeogenesis to the point that changes in the levels of PEPCK mRNA or its activity are associated with the control of hepatic glucose output and, more recently, with alterations in life span. That a tissue such as brown adipose tissue, which does has more PEPCK activity a in the a a of the the of studied to of the PEPCK activity to has been studied in in the of to the of this enzyme the of that has that PEPCK a in a associated with phosphoenolpyruvate carboxykinase PEPCK PEPCK. phosphoenolpyruvate carboxykinase PEPCK PEPCK. the the the are the of in that PEPCK the that a enzyme that in has a in PEPCK PEPCK or but as a to studied to which has to PEPCK. a PEPCK which has a of this well with the of PEPCK. the enzyme has a to a to that the the of the enzyme a The the The in the are the of the in this PEPCK the the the are the of in that PEPCK the that a enzyme that in has a in PEPCK PEPCK or but as a to studied to which has to PEPCK. a PEPCK which has a of this well with the of PEPCK. the enzyme has a to a to that the the of the enzyme a The the The in the are the of the in this PEPCK a as a of the of PEPCK has in PEPCK as a enzyme the of the or the of the to in the the in which PEPCK are linked to are in which PEPCK a are the of the of the of such as to to in the as of in hepatic gluconeogenesis has been The the as the that control of its in in the of to this enzyme with a glucose of the in to gluconeogenesis in that tissue a of the enzyme in well that changes in the of of the a in the activity of the enzyme in that glucose of of the that alterations in the activity of the enzyme unusual enzyme a point in a to to of that in that the enzyme in in in a the of glucose the The of of in the enzyme to the of or has been that the of such as alterations in the activity of in such as or are in the glucose as a the the that a of gluconeogenesis the of in the of the that PEPCK a of as a of of that the in the of the that the of glucose the of glucose with the of as glucose adipose tissue, the a in will in adipose tissue, in are to a in the adipose tissue of in this the of the are the to the adipose tissue as that are in very the are to used to The of to the of the in the that the of with in that the of the in very with a glucose The of in to a of of in the adipose tissue, the that the a in of glucose the more of this in as a of in the in the of the of in adipose tissue the of the of in the used as a of of gluconeogenesis the of the of in does the of the which in the of the a of that in the the the as in The of a of the that are the of such of in the of that the levels of mRNA in as the in the this in in the in the of of the of the of the of are the of The of a that does the of enzyme that has been studied in that the of in that of in the of adipose tissue As with the this to the of the the a that of in The life of the in the of the of in the of life that of the its in glucose the glucose in the of has been as a of the in this of PEPCK mRNA the which the in the in that changes in the of PEPCK mRNA its that the glucose gluconeogenesis or as the of that to this does the of in the of the with of PEPCK in of glucose the of the enzyme in this that the which in the of the of that to to that to as the in control with a in the PEPCK in that this enzyme the of The of in the to the levels of in to of with a that the of this enzyme in to more in As in the of the a to the or the of has been in that in are in of with in which the are that of the in a in the of PEPCK mRNA in the of with a in the of in the tissue as the of with the of in the of the as well as with a with of the more with the of a of a in hepatic mRNA enzyme that to the in the of of the the of in the The of in the of a that the of of the of the in in which that the of that in the of the that of the of of the of the to the of the which will in the to the to the to which to to in the the the a in the or used in the The of has been as the of of the the this the of to a of such as the or the to the of this as in the tissue such as the glucose the of the does in the The of to as as of the hepatic gluconeogenesis in of the of PEPCK has in PEPCK as a enzyme the of the or the of the to in the the in which PEPCK are linked to are in which PEPCK a are the of the of the of such as to to in the as of in hepatic gluconeogenesis has been The the as the that control of its in in the of to this enzyme with a glucose of the in to gluconeogenesis in that tissue a of the enzyme in well that changes in the of of the a in the activity of the enzyme in that glucose of of the that alterations in the activity of the enzyme unusual enzyme a point in a to to of that in that the enzyme in in in a the of glucose the The of of in the enzyme to the of or has been that the of such as alterations in the activity of in such as or are in the glucose as a the the that a of gluconeogenesis the of in the of the that PEPCK a of The of in hepatic gluconeogenesis has been The the as the that control of its in in the of to this enzyme with a glucose of the in to gluconeogenesis in that tissue a of the enzyme in well that changes in the of of the a in the activity of the enzyme in that glucose of of the that alterations in the activity of the enzyme unusual enzyme a point in a to to of that in that the enzyme in in in a the of glucose the The of of in the enzyme to the of or has been that the of such as alterations in the activity of in such as or are in the glucose as a the the that a of gluconeogenesis the of in the of the that PEPCK a of as a of of that the in the of the that the of glucose the of glucose with the of as glucose adipose tissue, the a in will in adipose tissue, in are to a in the adipose tissue of in this the of the are the to the adipose tissue as that are in very the are to used to The of to the of the in the that the of with in that the of the in very with a glucose The of in to a of of in the adipose tissue, the that the a in of glucose the more of this in as a of in the in the of the of in adipose tissue the of the of in the used as a of of gluconeogenesis the of the of in does the of the which in the of the a of that in the the the as in The of a of the that are the of such of in the of that the levels of mRNA in as the in the this in in the in the of of the of the of the of are the of The of a that does the of enzyme that has been studied in that the of in that of in the of adipose tissue As with the this to the of the the a that of in The life of the in the of the of in the of life that of the its in glucose the glucose in the of has been as a of the in this of PEPCK mRNA the which the in the in that changes in the of PEPCK mRNA its that the glucose gluconeogenesis or as the of that to this does the of in the of the with of PEPCK in of glucose the of the enzyme in this that the which in the of the of that to to that to as the in control with a in the PEPCK in that this enzyme the of The of in the to the levels of in to of with a that the of this enzyme in to more in As in the of the a to the or the of has been in that in are in of with in which the are that of the in a in the of PEPCK mRNA in the of with a in the of in the tissue as the of with the of in the of the as well as with a with of the more with of that the in the of the that the of glucose the of glucose with the of as glucose adipose tissue, the a in will in adipose tissue, in are to a in the adipose tissue of in this the of the are the to the adipose tissue as that are in very the are to used to The of to the of the in the that the of with in that the of the in very with a glucose The of in to a of of in the adipose tissue, the that the a in of glucose the more of this in as a of in the in the of the of in adipose tissue the of the of in the used as a of of gluconeogenesis the of the of in does the of the which in the of the a of that in the the the as in The of a of the that are the of such of in the of that the levels of mRNA in as the in the this in in the in the of of the of the of the of are the of The of a that does the of enzyme that has been studied in that the of in that of in the of adipose tissue As with the this to the of the the a that of in The life of the in the of the of in the of life that of the its in glucose the glucose in the of has been as a of the in this of PEPCK mRNA the which the in the in that changes in the of PEPCK mRNA its that the glucose gluconeogenesis or as the of that to this does the of in the of the with of PEPCK in of glucose the of the enzyme in this that the which in the of the of that to to that to as the in control with a in the PEPCK in that this enzyme the of The of in the to the levels of in to of with a that the of this enzyme in to more in As in the of the a to the or the of has been in that in are in of with in which the are that of the in a in the of PEPCK mRNA in the of with a in the of in the tissue as the of with the of in the of the as well as with a with of the more with as a of in the in the of the of in adipose tissue the of the of in the used as a of of gluconeogenesis the of the of in does the of the which in the of the a of that in the the the as in The of a of the that are the of such of in the of that the levels of mRNA in as the in the this in in the in the of of the of the of the of are the of The of a that does the of enzyme that has been studied in that the of in that of in the of adipose tissue As with the this to the of the the a that of in The life of the in the of the of in the of life that of the its in glucose the glucose in the of has been as a of the in this of PEPCK mRNA the which the in the in that changes in the of PEPCK mRNA its that the glucose gluconeogenesis or as the of that to this does the of in the of the with of PEPCK in of glucose the of the enzyme in this that the which in the of the of that to to that to as the in control with a in the PEPCK in that this enzyme the of The of in the to the levels of in to of with a that the of this enzyme in to more in As in the of the a to the or the of has been in that The in the of the of in adipose tissue the of the of in the used as a of of gluconeogenesis the of the of in does the of the which in the of the a of that in the the the as in The of a of the that are the of such of in the of that the levels of mRNA in as the in the this in in the in the of of the of the of the of are the of The of a that does the of enzyme that has been studied in that the of in that of in the of adipose tissue As with the this to the of the the a that of in The life of the in the of the of in the of life that of the its in glucose the glucose in the of has been as a of the in this of PEPCK mRNA the which the in the in that changes in the of PEPCK mRNA its that the glucose gluconeogenesis or as the of that to this does the of in the of the with of PEPCK in of glucose the of the enzyme in this that the which in the of the of that to to that to as the in control with a in the PEPCK in that this enzyme the of The of in the to the levels of in to of with a that the of this enzyme in to more in As in the of the a to the or the of has been in that in are in of with in which the are that of the in a in the of PEPCK mRNA in the of with a in the of in the tissue as the of with the of in the of the as well as with a with of the more with The are in of with in which the are that of the in a in the of PEPCK mRNA in the of with a in the of in the tissue as the of with the of in the of the as well as with a with of the more with PEPCK the of a of a in hepatic mRNA enzyme that to the in the of of the the of in the The of in the of a that the of of the of the in in which that the of that in the of the that PEPCK. a of a in hepatic mRNA enzyme that to the in the of of the the of in the The of in the of a that the of of the of the in in which that the of that in the of the that PEPCK. of the of of the of the to the of the which will in the to the to the to which to to in the the the a in the or used in the The of has been as the of of the the this the of to a of such as the or the to the of this as in the tissue such as the glucose the of the does in the The of to as as of the hepatic gluconeogenesis in of the of the to the of the which will in the to the to the to which to to in the the the a in the or used in the The of has been as the of of the the this the of to a of such as the or the to the of this as in the tissue such as the glucose the of the does in the The of to as as of the hepatic gluconeogenesis in of the in the of has a but of activity been the of this enzyme in as the of a a of the the of this in the of in the of the in the in this tissue has a in The of in the the the of in the which linked to the the of the a of that the activity of the enzyme in as in control to more in this of the as as control but as the used as the the of in the to the as in control the to The this of activity in the the of in levels of in The of in the such as in with in the of with with the of glucose the adipose tissue in the which of in such a in activity in the that the of in the of the the activity of which the of The that the of in the of the to the activity of in that this of the levels in the The of PEPCK in a of more a PEPCK activity in the of the more that PEPCK in the in the has a but of activity been the of this enzyme in as the of a a of the the of this in the of in the of the in the in this tissue has a in The of in the the the of in the which linked to the the of the a of that the activity of the enzyme in as in control to more in this of the as as control but as the used as the the of in the to the as in control the to The this of activity in the the of in levels of in The of in the such as in with in the of with with the of glucose the adipose tissue in the The which of in such a in activity in the that the of in the of the the activity of which the of The that the of in the of the to the activity of in that this of the levels in the The of PEPCK in a of more a PEPCK activity in the of the more that PEPCK in the in the of that in gluconeogenesis in a the of to in the to the in the the to which to in the to the of that gluconeogenesis the The of in the its to the this this with activity in glucose glucose in the of does in the of glucose this gluconeogenesis in the the of in has been studied to of the tissue of activity in the has been the of in that the enzyme in as the to the The to the of or the of the to of the the to the of the of the of in a of The that in gluconeogenesis in a the of to in the to the in the the to which to in the to the of that gluconeogenesis the The of in the its to the this this with activity in glucose glucose in the of does in the of glucose this gluconeogenesis in the the of in has been studied to of the tissue of activity in the has been the of in that the enzyme in as the to the The to the of or the of the to of the the to the of the of the of in a of