Dear Asim,
PEPCK Enzyme:
The enzyme phosphoenolpyruvate carboxykinase (GTP) (PEPCK)2 has the unusual distinction of being very well studied but metabolically misunderstood. 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 not make glucose, has more PEPCK activity on a protein basis than is present in the liver is largely ignored. In addition, all eukaryotes have a gene for both a mitochondrial (PEPCK-M) and cytosolic (PEPCK-C) form of the enzyme. In the livers of most mammals studied to date (including humans), 50% of the total PEPCK activity is PEPCK-M. For more on this enzyme, please see the following link:
http://www.jbc.org/content/284/40/27025
PEPCK Inhibitors:
The most known inhibitor for PEPCK is 3-mercaptopicolinic acid (MPA). For other inhibitors and mechanistic details, please see the following text and links:
For almost four decades, it has been known that tryptophan metabolites and picolinic acid analogues act as inhibitors of gluconeogenesis. Early studies observed that 3-mercaptopicolinic acid (MPA) was a potent hypoglycemic agent via inhibition of glucose synthesis through the specific inhibition of phosphoenolpyruvate carboxykinase (PEPCK) in the gluconeogenesis pathway. To clarify the mechanism of inhibition exerted by MPA on PEPCK, structural and kinetic studies have been carried out. The kinetic data in concert with crystallographic structures of PEPCK in complex with MPA and the substrates for the reaction illustrate that PEPCK is inhibited by the binding of MPA at two discrete binding sites: one acting in a competitive fashion with PEP/OAA (∼10 μM) and the other acting at a previously unidentified allosteric site (Ki ∼ 150 μM). The structural studies suggest that binding of MPA to the allosteric pocket stabilizes an altered conformation of the nucleotide-binding site that in turn reduces the affinity of the enzyme for the nucleotide.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3398862/
http://www.jbc.org/content/251/1/37.full.pdf
Hoping this will be helpful,
Rafik
Asim, if you do really wish to learn (as in understand) the field, a better approach will be to review the relevant literature, which spans quite a few years, and then ask more specific questions that may be confounding to you.
Expecting others to do a review of literature for you may seem convenient but it has its own serious limitations.
Thank you Prof. Rafik Karaman for sharing your views on PEPCK. It will definitely help me a lot.
Mr. Alam, thank you for your reply. An expert would not do literature review to answer my question. Having completed my PhD in PEPCK, I was expecting an expert opinion like of Prof. Karaman in this field.
"Having completed my PhD in PEPCK, I was expecting an expert opinion like of Prof. Karaman in this field."
The portions of the above statement have no bearing on each other but I am happy that you found what you were expecting.
Puzzling that having finished your PhD in PEPCK, you seem to be unaware of well-known inhibitors of the enzyme...
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