School Of Basic And Applied Sciences

Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/17

Browse

Subject: search.filters.subject.Glycolysis

Search Results

Now showing 1 - 4 of 4
  • No Thumbnail Available
    Item
    A Perspective on Medicinal Chemistry Approaches for Targeting Pyruvate Kinase M2
    (American Chemical Society, 2021-11-02T00:00:00) Arora, Sahil; Joshi, Gaurav; Chaturvedi, Anuhar; Heuser, Michael; Patil, Santoshkumar; Kumar, Raj
    The allosteric regulation of pyruvate kinase M2 (PKM2) affects the switching of the PKM2 protein between the high-activity and low-activity states that allow ATP and lactate production, respectively. PKM2, in its low catalytic state (dimeric form), is chiefly active in metabolically energetic cells, including cancer cells. More recently, PKM2 has emerged as an attractive target due to its role in metabolic dysfunction and other interrelated conditions. PKM2 (dimer) activity can be inhibited by modulating PKM2 dimer�tetramer dynamics using either PKM2 inhibitors that bind at the ATP binding active site of PKM2 (dimer) or PKM2 activators that bind at the allosteric site of PKM2, thus activating PKM2 from the dimer formation to the tetrameric formation. The present perspective focuses on medicinal chemistry approaches to design and discover PKM2 inhibitors and activators and further provides a scope for the future design of compounds targeting PKM2 with better efficacy and selectivity. � 2021 American Chemical Society
  • No Thumbnail Available
    Item
    A short review on cross-link between pyruvate kinase (PKM2) and Glioblastoma Multiforme
    (Springer, 2021-03-02T00:00:00) Verma, Harkomal; Cholia, Ravi P.; Kaur, Sharanjot; Dhiman, Monisha; Mantha, Anil K.
    Pyruvate kinase (PK) catalyzes the last irreversible reaction of glycolysis pathway, generating pyruvate and ATP, from Phosphoenol Pyruvate (PEP) and ADP precursors. In mammals, four different tissue-specific isoforms (M1, M2, L and R) of PK exist, which are translated from two genes (PKL and PKR). PKM2 is the highly expressed isoform of PK in cancers, which regulates the aerobic glycolysis via reprogramming cancer cell�s metabolic pathways�to provide an anabolic�advantage to the tumor cells. In addition to the established role of PKM2 in aerobic glycolysis of multiple cancer types, various recent findings have highlighted the non-metabolic functions of PKM2 in brain tumor development. Nuclear PKM2 acts as a co-activator and directly regulates gene transcription. PKM2 dependent transactivation of various oncogenic genes is instrumental in the progression and aggressiveness of Glioblastoma Multiforme (GBM). Also, PKM2 acts as a protein kinase in histone modification which regulates gene expression and tumorigenesis. Ongoing research has explored novel regulatory mechanisms of PKM2 and its association in GBM progression. This review enlists and summarizes the metabolic and non-metabolic roles of PKM2 at the cellular level, and its regulatory function highlights the importance of the nuclear functions of PKM2 in GBM progression, and an emerging role of PKM2 as novel cancer therapeutics. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
  • No Thumbnail Available
    Item
    A short review on cross-link between pyruvate kinase (PKM2) and Glioblastoma Multiforme
    (Springer, 2021-03-02T00:00:00) Verma, Harkomal; Cholia, Ravi P.; Kaur, Sharanjot; Dhiman, Monisha; Mantha, Anil K.
    Pyruvate kinase (PK) catalyzes the last irreversible reaction of glycolysis pathway, generating pyruvate and ATP, from Phosphoenol Pyruvate (PEP) and ADP precursors. In mammals, four different tissue-specific isoforms (M1, M2, L and R) of PK exist, which are translated from two genes (PKL and PKR). PKM2 is the highly expressed isoform of PK in cancers, which regulates the aerobic glycolysis via reprogramming cancer cell�s metabolic pathways�to provide an anabolic�advantage to the tumor cells. In addition to the established role of PKM2 in aerobic glycolysis of multiple cancer types, various recent findings have highlighted the non-metabolic functions of PKM2 in brain tumor development. Nuclear PKM2 acts as a co-activator and directly regulates gene transcription. PKM2 dependent transactivation of various oncogenic genes is instrumental in the progression and aggressiveness of Glioblastoma Multiforme (GBM). Also, PKM2 acts as a protein kinase in histone modification which regulates gene expression and tumorigenesis. Ongoing research has explored novel regulatory mechanisms of PKM2 and its association in GBM progression. This review enlists and summarizes the metabolic and non-metabolic roles of PKM2 at the cellular level, and its regulatory function highlights the importance of the nuclear functions of PKM2 in GBM progression, and an emerging role of PKM2 as novel cancer therapeutics. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
  • Thumbnail Image
    Item
    In Silico Identification of Novel Natural Inhibitors Of Carbohydrate Metabolic Pathway In Cancer Cells
    (Central University of Punjab, 2018) Dash, Swastika; Kumar, Shashank
    Carbohydrate metabolism in cancer cells is linked to the 'Warburg Effect' which states that, under aerobic conditions, cancer cells metabolize approximately ten fold more glucose to lactate in a given time than normal cells; typically altered glycolytic pathway regulation. This has made the blocking of glycolytic pathway enzymes, a fascinating strategy to find treatment for cancer. This project addresses in a comprehensive manner the main glycolytic enzymes accounting for high-rate glycolysis in cancer cells. In addition, highlights of inhibitors that can be used to target the particular enzymes to decrease proliferation have also been done. Furthermore, besides the known inhibitors, receptor-based molecular docking of certain methylated flavonoids was performed with the proteins (isozymes of carbohydrate metabolic pathway enzymes) to find the lead inhibitors. The proteins used in the study are GLUT1 (4PYP), Hexokinase2 (2NZT), Phosphofructokinase2 (2AXN), Pyruvate kinaseM2 (3GQY), Lactate dehydrogenase A (4AJP) and Enolase2 (5IDZ). The dock scores were in the range of -5.88 to -9.68 against different target proteins. The methylated flavonoids 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4H-chromen- 4-one, 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-6,8-dimethoxy-4H-chromen-4- one, 2-(3,4-dimethylphenyl)-5,7-dimethyl-4H-chromen-4-one and 6-hydroxy-3,5,7,8- tetramethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one showed better dock scores for the target proteins in comparison to the standard inhibitors. Thus these methylated flavonoids might be considered promising leads for further development of glycolytic pathway inhibitors in cancer cells.