China
Africa
Explore chapters and articles related to this topic
Fructose-1,6-diphosphatase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
The enzyme FDP (EC 3.1.3.11) provides an essential step in the pathway of gluconeogenesis (Figure 49.1). The enzyme catalyzes the irreversible conversion of fructose-1,6-diphosphate to fructose-6-phosphate. Another enzyme, phosphofructokinase, and adenosine triphosphate (ATP) are required to take this reaction in the reverse direction. The enzyme is most active in liver and kidney; and the liver enzyme is highly regulated [4]. Deficiency has most often been documented in the biopsied liver. The gene (FBP1) has been cloned and localized to chromosome 9q22.2-22.3 [5]. Seven exons span 31 kb. The common mutation in Japanese people is an insertion, 960–961insG [6], which was also the most frequent mutation in a non-Japanese population [7, 8]. This mutation causes a frameshift and premature chain termination, as does 966del, and expression studies have shown both to be pathogenic. The disease is clearly genetically heterogeneous and a variety of other mutations has been found.
Mitochondrial Dysfunction in Breast Cancer
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Thalita Basso Scandolara, Letícia Madureira Pacholak, Thayse Fachin Cormanique, Rodrigo Kern, Carolina Panis
There is evidence that the adaptor protein, MITA, inhibits the turnover of mitochondria through mitophagy and decreases the mitochondrial biogenesis by downregulating PGC1α, leading to an accumulation of damaged mitochondria and acting as a tumor suppressor (Bhatelia et al. 2017). Another potential tumor suppressor and possibly a mitophagy regulator in breast cancer is FBP1, an enzyme involved in gluconeogenesis. It has been suggested that higher expression of FBP1 is capable of promoting apoptosis in breast cancer cell lines MCF-7 and MDA-MB-231; furthermore, that both groups had elevated levels of pro-apoptotic proteins. Besides, FBP1 acts as a mitophagy suppressor by blocking HIF1a/BNIP3 pathway and enhancing the association between Beclin 1 and Bcl-2, causing inhibition of mitophagy, causing an accumulation of ROS levels and consequently an intensification of apoptosis rate in tumor cells (Liu et al. 2017a).
Glycometabolic rearrangements–aerobic glycolysis in pancreatic ductal adenocarcinoma (PDAC): roles, regulatory networks, and therapeutic potential
Published in Expert Opinion on Therapeutic Targets, 2021
Enhanced glycolysis is well known to be closely associated with resistance to tumor therapy [83]. Many studies have demonstrated a link between enhanced glycolysis and therapy resistance in a variety of cancers, including PDAC [84–87]. Enhanced glycolysis in PDAC was shown to promote resistance to gemcitabine, whereas the application of 2DG, an inhibitor of glycolysis, reversed this effect [87]. According to the published studies, the mechanisms by which aerobic glycolysis influences therapy sensitivity of PDAC can be summarized as follows. (1) HK2, a key enzyme of glycolysis, is induced to dimerize and combine with voltage‐dependent anion channels by ROS derived from gemcitabine, leading to resistance to gemcitabine [88]. (2) Fructose-1,6-bisphosphatase (FBP1), a key enzyme in gluconeogenesis, helps to convert fructose-1,6-bisphosphate to fructose-6-phosphate [18]. Loss of FBP1 in PDAC activates the IQGAP1–extracellular regulatory protein kinase (ERK)–Myc axis, causing resistance to gemcitabine [89]. (3) Upregulation of mucin-1 (MUC1), an oncogene in various cancers and a contributor to glycometabolic rearrangements in PDAC, promotes glycolysis, the pentose phosphate pathway, and nucleotide biosynthesis pathways [90]. Thus, DNA damage repair is enhanced, facilitating resistance to radiotherapy [91].
Impacts of high-sucrose diet on circadian rhythms in the small intestine of rats
Published in Chronobiology International, 2019
Shumin Sun, Fumiaki Hanzawa, Miki Umeki, Yasuko Matsuyama, Naomichi Nishimura, Saiko Ikeda, Satoshi Mochizuki, Hiroaki Oda
After being transported into epithelial cells, the sucrose-derived monosaccharides, glucose and fructose, are metabolized via different pathways. Recently, Jang et al. found that a limited amount of fructose is catabolized completely by the small intestine and gut bacteria, while high doses of fructose still spill over into the liver to be metabolized (Jang et al. 2018). Our results showed that expression of KHK (ketohexokinase) showed little changes in response to the high-sucrose diet (Figure 3i, Supplementary Table S2). Several rate-limiting enzymes of glycolysis, such as GCK (glucokinase), PFKL (phosphofructokinase), and PKLR (pyruvate kinase), exhibited little alteration in gene expression oscillations between the groups (Figure 3j–l, Supplementary Table S2), while expression of G6PC (glucose-6-phosphatase, catalytic subunit) and FBP1 (fructose-1, 6-bisphosphatase), which play important roles in gluconeogenesis, significantly increased in response to the high-sucrose diet (Figure 3m and n, Supplementary Table S2). As expression of PEPCK (phosphoenolpyruvate carboxykinase) did not change (Figure 3o, Supplementary Table S2) in response to the high-sucrose diet, gluconeogenesis from non-carbohydrate molecules was likely not increased. However, the small intestine may have worked to convert fructose metabolite, such as dihydroxyacetone phosphate and glyceraldehyde, into glucose.
Impact of heart-specific disruption of the circadian clock on systemic glucose metabolism in mice
Published in Chronobiology International, 2018
Tomomi Nakao, Akira Kohsaka, Tsuyoshi Otsuka, Zaw Lin Thein, Hue Thi Le, Hidefumi Waki, Sabine S Gouraud, Hayato Ihara, Masako Nakanishi, Fuyuki Sato, Yasuteru Muragaki, Masanobu Maeda
Given that hepatic gluconeogenesis is a major source of glucose overproduction in insulin resistant conditions, we examined the mRNA expression levels of genes encoding key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-biphosphatase (FBPase), and glucose-6-phosphatase (G6Pase), in the liver tissues of H-Bmal1−/− mice. We first used the liver tissues of intact control and H-Bmal1−/− mice to analyze Pck1 (encoding cytosolic PEPCK), Fbp1 (encoding FBPase), and G6pc (encoding G6Pase) expression levels and found no significant differences in the expression of these genes between the groups (Figure 5A). However, when insulin was administered, G6Pc expression was significantly higher in H-Bmal1−/− mice than control animals; however, the expression of other gluconeogenic genes (i.e., Pck1 and Fbp1) did not differ (Figure 5B). This finding indicated that G6Pc expression was not fully suppressed by insulin in the liver of H-Bmal1−/− mice. H-Bmal1−/− mice also showed a decreased action of insulin on the liver at the signal transduction level. We examined insulin-induced phosphorylation of Akt in the liver and observed a decrease in phosphorylated Akt levels in the livers of H-Bmal1−/− mice compared with control mice (Figure 5C). The reproducibility of this observation was confirmed in two independent immunoblots (Supplemental Figure 3). Collectively, these findings revealed that dysfunction of the molecular clock in the heart leads to a decreased action of insulin on hepatic glucose metabolism.