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Three Glycolysis reactions have such a large negative  G that they are essentially irreversible.  Hexokinase (or Glucokinase)  Phosphofructokinase.

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Presentasi berjudul: "Three Glycolysis reactions have such a large negative  G that they are essentially irreversible.  Hexokinase (or Glucokinase)  Phosphofructokinase."— Transcript presentasi:

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2 Three Glycolysis reactions have such a large negative  G that they are essentially irreversible.  Hexokinase (or Glucokinase)  Phosphofructokinase  Pyruvate Kinase. Pyruvate Kinase (last step of Glycolysis) catalyzes: phosphoenolpyruvate + ADP  pyruvate + ATP

3  Piruvat Kinase adalah enzim yang mengkatalisis langkah irreversibel ketiga pada glikolisis  Piruvat Kinase menghasilkan ATP dan Piruvat  Bila muatan energi tinggi, ATP secara allosterik menginhibisi Piruvat Kinase untuk memperlambat glikolisis

4 Piruvat Kinase terfosforilasi (kurang aktif) Piruvat Kinase terdesfosforilasi (lebih aktif) PIPI H2OH2O Kadar glukosa darah merah ADP ATP - + Fosfoenolpiruvat + ADP +H + Piruvat + ATP Fruktosa 1,6- bisfosfat ATP Alanin + -

5  Alanin secara allosterik menghambat piruvat kinase  Bila kadar glukosa darah menurun, glukagon memicu kaskade AMP siklik yang menyebabkan fosforilasi Piruvat Kinase, yang mengurangi aktivitasnya  Fosforilasi ini seperti enzim bifungsi yang mengontrol kadar fruktosa 2,6-bisfosfat

6  Fruktosa 2,6-bisfosfat dibentuk melalui fosforilasi senyawa fruktosa 6-fosfat oleh enzim fosfofruktokinase-2  dalam keadaan glukosa yang berlimpah, konsentrasi senyawa fruktosa 2,6-bisfosfat akan meningkat sehingga merangsang glikolisis dengan mengaktifkan fosfofruktokinase-1 dan menghambat fruktosa-1,6- bisfosfatase.  Dalam keadaan kekurangan glukosa, glukoneogenesis dirangsang oleh penurunan konsentrasi fruktosa 2,6-bisfosfat yang kemudian menghilangkan aktivitas fosfofruktokinase-1 dan meniadakan penghambatan kerja fruktosa-1, 6- bisfosfatase.

7  Pyruvate Carboxylase (pyruvate  oxaloactate) is allosterically activated by acetyl CoA.  [Oxaloacetate] tends to be limiting for Krebs cycle.

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9 Enzymes relevant to these pathways that are phosphorylated by Protein Kinase A include:  Pyruvate Kinase, a glycolysis enzyme that is inhibited when phosphorylated.  CREB (cAMP response element binding protein) which activates, through other factors, transcription of the gene for PEP Carboxykinase, leading to increased gluconeogenesis.  A bi-functional enzyme that makes and degrades an allosteric regulator, fructose-2,6-bisphosphate.

10  PFK activity in the presence of the globally controlled allosteric regulator fructose-2,6-bisphosphate is similar to that at low ATP.  Fructose-2,6-bisphosphate promotes the relaxed state, activating Phosphofructokinase even at high [ATP].  Thus activation by fructose-2,6-bisphosphate, whose concentration fluctuates in response to external hormonal signals, supersedes local control by [ATP].


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