Inhibiting Hexamer Disassembly of Human UDP-Glucose Dehydrogenase by Photoactivated Amino Acid Cross-Linking

Grady, George; Thelen, Ashley M.; Albers, Jaleen; Ju, Tao; Guo, Jiantao; Barycki, Joseph J.; Simpson, Melanie A.

doi:10.1021/acs.biochem.6b00259

Cited by 8 publications

(4 citation statements)

References 26 publications

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“…The enzyme UDP–glucose dehydrogenase encoded by the gene UGDH converts UDP–glucose into UDP–glucuronate through two successive NAD + -dependent oxidation steps [ 38 ]. Human UDP–glucose dehydrogenase apoprotein has been purified [ 39 ]. Glucuronate residues derived from UDP–glucuronate are attached to endogenous molecules such as bilirubin and foreign compounds such as acetaminophen to assist in their elimination.…”

Section: Hepatic Glucose Utilizationmentioning

confidence: 99%

Liver glucose metabolism in humans

Adeva‐Andany¹,

Pérez-Felpete²,

et al. 2016

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Information about normal hepatic glucose metabolism may help to understand pathogenic mechanisms underlying obesity and diabetes mellitus. In addition, liver glucose metabolism is involved in glycosylation reactions and connected with fatty acid metabolism. The liver receives dietary carbohydrates directly from the intestine via the portal vein. Glucokinase phosphorylates glucose to glucose 6-phosphate inside the hepatocyte, ensuring that an adequate flow of glucose enters the cell to be metabolized. Glucose 6-phosphate may proceed to several metabolic pathways. During the post-prandial period, most glucose 6-phosphate is used to synthesize glycogen via the formation of glucose 1-phosphate and UDP–glucose. Minor amounts of UDP–glucose are used to form UDP–glucuronate and UDP–galactose, which are donors of monosaccharide units used in glycosylation. A second pathway of glucose 6-phosphate metabolism is the formation of fructose 6-phosphate, which may either start the hexosamine pathway to produce UDP-N-acetylglucosamine or follow the glycolytic pathway to generate pyruvate and then acetyl-CoA. Acetyl-CoA may enter the tricarboxylic acid (TCA) cycle to be oxidized or may be exported to the cytosol to synthesize fatty acids, when excess glucose is present within the hepatocyte. Finally, glucose 6-phosphate may produce NADPH and ribose 5-phosphate through the pentose phosphate pathway. Glucose metabolism supplies intermediates for glycosylation, a post-translational modification of proteins and lipids that modulates their activity. Congenital deficiency of phosphoglucomutase (PGM)-1 and PGM-3 is associated with impaired glycosylation. In addition to metabolize carbohydrates, the liver produces glucose to be used by other tissues, from glycogen breakdown or from de novo synthesis using primarily lactate and alanine (gluconeogenesis).

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Section: Hepatic Glucose Utilizationmentioning

confidence: 99%

Liver glucose metabolism in humans

Adeva‐Andany¹,

Pérez-Felpete²,

et al. 2016

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“…These proteins with a glycolysis function have common characteristics to form homo-oligomer and their function and localization were known to differ based on their forms (2,8,25,36). The wild-type UGDH forms homo-oligomers like moonlighting proteins (15,16). In this study, we firstly clarified that its function markedly differed based on its sub-cellular localization, suggesting that UGDH might be a moonlighting protein.…”

Section: Discussionmentioning

confidence: 81%

<b>Clinicopathological and prognostic significance of nuclear UGDH localization in lung adenocar</b><b>cinoma</b>

et al. 2019

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This study aimed to clarify relationships among UDP-glucose-6 dehydrogenase (UGDH) expression, clinicopathological factors, and the prognosis of patients, and to determine the role of UGDH in lung adenocarcinoma (AC). Firstly, UGDH expression and localization in 126 lung AC tissues were immunohistochemically studied, and associations with clinicopathological parameters and patients' prognosis were evaluated. Secondly, serum UGDH levels were measured in 267 lung cancer patients and 100 healthy controls. Finally, the effects of UGDH knockdown by siRNA on migration and invasion abilities were analyzed. As a result, nuclear UGDH staining was significantly correlated with poorer differentiation, a larger tumor size, higher p-TNM stage, positive nodal metastasis, positive lymphatic invasion, and positive vascular invasion in lung AC patients. Nuclear UGDH-positive patients showed significantly poorer survival than nuclear UGDH-negative patients. Serum UGDH levels were especially higher in lung AC patients even in stage I than those in healthy controls. In lung AC cell lines, nuclear expression levels of UGDH were higher in LC-2/ad cells than in A549 cells. UGDH siRNA-treated LC-2/ad cells showed significantly decreased migration and invasion abilities, but no significant differences were observed in UGDH siRNA-treated A549 cells. These data indicate that UGDH expression and localization are an early sero-diagnostic marker in addition to a poor prognostic indicator in lung AC patients.

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“…UDP-glucose dehydrogenase serves as a metabolic enzyme and converts UDP-glucose to UDP-glucuronic acid, which is an initial step in the synthesis of GAGs. 50 GAGs including chondroitin sulphate, dermatan sulphate, heparin sulphate and hyaluronan are the major components of extracellular matrix that participate in regulating several cancer cell behaviours, such as invasion, migration and angiogenesis. 51 Chondroitin sulphate binds to fibroblast growth factor-2…”

Section: Control Shugdhmentioning

confidence: 99%