General Information of MET (ID: META00422)
Name Glucose 6-phosphate
Synonyms   Click to Show/Hide Synonyms of This Metabolite
6-O-Phosphono-D-glucopyranose; D(+)-Glucopyranose 6-phosphate; D-Glucose 6-phosphate; D-Glucose 6-phosphoric acid; D-Glucose-6-dihydrogen phosphate; D-Hexose 6-phosphate; GLC6p; Glucose 6-phosphoric acid; Glucose-6-phosphate; Robison ester; a-D-Glucose 6- phosphate; alpha-D-Glucose 6- phosphate; alpha-D-Glucose 6-phosphate; alpha-D-Hexose 6-phosphate
Source Endogenous;Escherichia Coli Metabolite;Yeast Metabolite;Food;Microbial
Structure Type   Carbohydrates and carbohydrate conjugates  (Click to Show/Hide the Complete Structure Type Hierarchy)
Organic oxygen compounds
Organooxygen compounds
Carbohydrates and carbohydrate conjugates
PubChem CID
5958
HMDB ID
HMDB0001401
Formula
C6H13O9P
Structure
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3D MOL 2D MOL
  Click to Show/Hide the Molecular/Functional Data (External Links/Property/Function) of This Metabolite
KEGG ID
C00092
ChEBI ID
4170
FooDB ID
FDB021818
ChemSpider ID
5743
METLIN ID
145
Physicochemical Properties Molecular Weight 260.14 Topological Polar Surface Area 157
XlogP -4.2 Complexity 277
Heavy Atom Count 16 Rotatable Bond Count 3
Hydrogen Bond Donor Count 6 Hydrogen Bond Acceptor Count 9
Function
Glucose 6-phosphate (G6P) has two anomers: the alpha anomer and the beta anomer. Glucose 6-phosphate is an ester of glucose with phosphoric acid, made in the course of glucose metabolism by mammalian and other cells. It is a normal constituent of resting muscle and probably is in constant equilibrium with fructose 6-phosphate (Stedman, 26th ed). Glucose 6-phosphate is a phosphorylated glucose molecule on carbon 6. When glucose enters a cell, it is immediately phosphorylated to G6P. This is catalyzed with hexokinase enzymes, thus consuming one ATP. A major reason for immediate phosphorylation of the glucose is so that it cannot diffuse out of the cell. The phosphorylation adds a charged group so the G6P cannot easily cross cell membranes. G6P can travel down two metabolic pathways: glycolysis and the pentose phosphate pathway. In addition to the metabolic pathways, G6P can also be stored as glycogen in the liver if blood glucose levels are high. If the body needs energy or carbon skeletons for syntheses, G6P can be isomerized to fructose 6-phosphate and then phosphorylated to fructose 1,6-bisphosphate. Note, the molecule now has 2 phosphoryl groups attached. The addition of the 2nd phosphoryl group is an irreversible step, so once this happens G6P will enter glycolysis and be turned into pyruvate (ATP production occurs). If blood glucose levels are high, the body needs a way to store the excess glucose. After being converted to G6P, phosphoglucose mutase (an isomerase) can turn the molecule into glucose 1-phosphate. Glucose 1-phosphate can then be combined with uridine triphosphate (UTP) to form UDP-glucose. This reaction is driven by the hydrolysis of pyrophosphate that is released in the reaction. Now, the activated UDP-glucose can add to a growing glycogen molecule with the help of glycogen synthase. This is a very efficient storage mechanism for glucose since it costs the body only 1 ATP to store the 1 glucose molecule and virtually no energy to remove it from storage. It is important to note that glucose 6-phosphate is an allosteric activator of glycogen synthase, which makes sense because when the level of glucose is high the body should store the excess glucose as glycogen. On the other hand, glycogen synthase is inhibited when it is phosphorylated by protein kinase during times of high stress or low blood glucose levels.
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      GPCR rhodopsin (GPCR-1)
            Adrenergic receptor beta-3 (ADRB3) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Agonist (CL-316,243) of Adrb3
                      Induced Change Glucose 6-phosphate concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that agonist of ADRB3 leads to the increase of glucose 6-phosphate levels compared with control group.
      Hydrolases (EC 3)
            Leukotriene-C4 hydrolase (GGT1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockdown (siRNA) of GGT1
                      Induced Change Glucose 6-phosphate concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Renal cell carcinoma [ICD-11: 2C90]
                      Details It is reported that knockdown of GGT1 leads to the increase of glucose 6-phosphate levels compared with control group.
            Sulfatase sulf-1 (SULF1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Knockdown (shRNA) of SULF1
                      Induced Change Glucose 6-phosphate concentration: increase (FC = 10.68)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Ovarian cancer [ICD-11: 2C73]
                      Details It is reported that knockdown of SULF1 leads to the increase of glucose 6-phosphate levels compared with control group.
      Organophosphate:Pi antiporter (OPA)
            Glucose-6-phosphate translocase (SLC37A4) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [4]
                      Introduced Variation Overexpression of SLC37A4
                      Induced Change Glucose 6-phosphate concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC37A4 leads to the increase of glucose 6-phosphate levels compared with control group.
      Sugar transporter (ST)
            Facilitated glucose transporter 1 (SLC2A1A) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Downregulation of slc2a1a caused by Yap loss-of-function mutation
                      Induced Change Glucose 6-phosphate concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that downregulation of slc2a1a caused by Yap loss-of-function mutation leads to the decrease of glucose 6-phosphate levels compared with control group.
      Transcription factor (TF)
            Forkhead box protein O1 (FOXO1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [6]
                      Introduced Variation Overexpression of Foxo1
                      Induced Change Glucose 6-phosphate concentration: increase (FC = 3.10)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of Foxo1 leads to the increase of glucose 6-phosphate levels compared with control group.
            Myc proto-oncogene protein (MYC) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [7]
                      Introduced Variation Knockdown (siRNA) of MYC
                      Induced Change Glucose 6-phosphate concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockdown of MYC leads to the decrease of glucose 6-phosphate levels compared with control group.
      Transcriptional coactivator (TC)
            Transcriptional coactivator YAP1 (yap1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Decrease of Yap mRNA caused by Yap loss-of-function mutation
                      Induced Change Glucose 6-phosphate concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that decrease of Yap mRNA caused by Yap loss-of-function mutation leads to the decrease of glucose 6-phosphate levels compared with control group.
      Transferases (EC 2)
            Acetylglucosaminyltransferase 5 (MGAT5) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Knockout of Mgat5
                      Induced Change Glucose 6-phosphate concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of Mgat5 leads to the decrease of glucose 6-phosphate levels compared with control group.
            Pyridoxal kinase (PDXK) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [9]
                      Introduced Variation Knockout (CRISPR/Cas9 sgRNA) of Pdxk
                      Induced Change Glucose 6-phosphate concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Acute myeloid leukaemia [ICD-11: 2A60]
                      Details It is reported that knockout of Pdxk leads to the decrease of glucose 6-phosphate levels compared with control group.
            Transaldolase (TALDO1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [10]
                      Introduced Variation Knockout of Taldo1
                      Induced Change Glucose 6-phosphate concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of Taldo1 leads to the increase of glucose 6-phosphate levels compared with control group.
References
1 Metabolic changes in adipose tissues in response to 3 -adrenergic receptor activation in mice. J Cell Biochem. 2019 Jan;120(1):821-835.
2 Impairment of gamma-glutamyl transferase 1 activity in the metabolic pathogenesis of chromophobe renal cell carcinoma. Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):E6274-E6282.
3 HSulf-1 deficiency dictates a metabolic reprograming of glycolysis and TCA cycle in ovarian cancer. Oncotarget. 2015 Oct 20;6(32):33705-19.
4 SLC37A1 and SLC37A2 are phosphate-linked, glucose-6-phosphate antiporters. PLoS One. 2011;6(9):e23157.
5 Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth. EMBO J. 2018 Nov 15;37(22):e100294.
6 Metabolomic analysis of C2C12 myoblasts induced by the transcription factor FOXO1. FEBS Lett. 2019 Jun;593(12):1303-1312.
7 Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC. Proc Natl Acad Sci U S A. 2017 Sep 12;114(37):E7697-E7706.
8 N-glycan remodeling on glucagon receptor is an effector of nutrient sensing by the hexosamine biosynthesis pathway. J Biol Chem. 2014 Jun 6;289(23):15927-41.
9 Vitamin B6 Addiction in Acute Myeloid Leukemia. Cancer Cell. 2020 Jan 13;37(1):71-84.e7.
10 Two isoforms of TALDO1 generated by alternative translational initiation show differential nucleocytoplasmic distribution to regulate the global metabolic network. Sci Rep. 2016 Oct 5;6:34648.

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