The metabolic and biochemical impact of glucose 6-sulfonate (sulfoquinovose), a dietary sugar, on carbohydrate metabolism.
Increased activity of the main carbohydrate pathways (glycolysis, pentose phosphate, and hexosamine biosynthetic pathways) is one of the hallmarks of metabolic diseases such as cancer. Sulfoquinovosyl diacylglycerol is a sulfoglycolipid found in the human diet that possesses anticancer activity that is absent when its carbohydrate moiety (glucose 6-sulfonate or sulfoquinovose) is removed. This work used bacterial systems to further understand the metabolism of this sugar through three main carbohydrate processing pathways and how this could influence its biological activity. Using (13)C NMR spectroscopy and enzyme assays, we showed that glucose 6-sulfonate cannot enter the pentose phosphate pathway, hence decreasing pentose and nucleotide biosyntheses. In glycolysis, glucose 6-sulfonate only provides one pyruvate per monosaccharide molecule, decreasing the flux of this pathway by half when compared to glucose 6-phosphate. Glucose 6-sulfonate can enter the hexosamine biosynthetic pathway by producing glucosamine 6-sulfonate, which is a reported antibacterial agent that competitively inhibits hexosamine production. All these interactions with carbohydrate routes might help explain the observed anticancer activity that glucose 6-sulfonate has in vitro. This adds to our knowledge of how vegetables rich in glucose 6-sulfonate can also act as metabolic inhibitors of pathways that are increased in metabolic diseases.
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, United States. sacomanj@msu.edu
Juliana L
JL
Sacoman
Lauren N
LN
Badish
Thomas D
TD
Sharkey
Rawle I
RI
Hollingsworth
D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism* / Q000494:pharmacology; D002247:Carbon Isotopes; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D005944:Glucosamine / Q000031:analogs & derivatives / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006595:Hexosamines / Q000096:biosynthesis*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008757:Methylglucosides / Q000378:metabolism* / Q000494:pharmacology; D009711:Nucleotides / Q000378:metabolism; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D010429:Pentoses / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D002247:Carbon Isotopes; D006595:Hexosamines; D008757:Methylglucosides; D009711:Nucleotides; D010429:Pentoses; C009358:sulfoquinovose; D019298:Glucose-6-Phosphate; D019289:Pyruvic Acid; D005944:Glucosamine