scholarly journals 6-Phosphogluconate Dehydrogenase Links Cytosolic Carbohydrate Metabolism to Protein Secretion

2018 ◽  
Author(s):  
Haoxin Li ◽  
Maria Ericsson ◽  
Bokang Rabasha ◽  
Bogdan Budnik ◽  
Bridget Wagner ◽  
...  
Keyword(s):  
Carbohydrate Metabolism ◽  
Protein Secretion ◽  
Metabolic Pathways ◽  
Structural Integrity ◽  
Computational Approach ◽  
Cell Stress ◽  
Phosphogluconate Dehydrogenase ◽  
Genetic Suppression ◽  
Cancer Cell Survival ◽  
Chemical Inhibition

SUMMARYThe proteinaceous extracellular matrix (ECM) is vital for cancer cell survival, proliferation, migration, and differentiation. However, little is known regarding metabolic pathways required in the ECM secretion process. By using an unbiased computational approach, we searched for enzymes whose suppression may lead to disruptions in protein secretion. Here, we show that 6-phosphogluconate dehydrogenase (PGD), a cytosolic enzyme involved in carbohydrate metabolism, is required for endoplasmic reticulum (ER) structural integrity and protein secretion. Chemical inhibition or genetic suppression of its activity led to cell stress accompanied by significantly expanded ER volume and can be rescued by compensating glutathione supplies. Our results also suggest that this characteristic ER-dilation phenotype may be a general marker indicating increased ECM protein congestion inside cells and decreased secretion. Thus, PGD exemplifies a nexus of cytosolic carbohydrate metabolism and protein secretion.

scholarly journals 6-Phosphogluconate Dehydrogenase Links Cytosolic Carbohydrate Metabolism to Protein Secretion via Modulation of Glutathione Levels

2019 ◽  
Vol 26 (9) ◽  
pp. 1306-1314.e5 ◽  
Author(s):  
Haoxin Li ◽  
Maria Ericsson ◽  
Bokang Rabasha ◽  
Bogdan Budnik ◽  
Sze Ham Chan ◽  
...  
Keyword(s):  
Carbohydrate Metabolism ◽  
Protein Secretion ◽  
Phosphogluconate Dehydrogenase

Enzyme Activities of NADPH-Forming Metabolic Pathways in Normal and Leukemic Leukocytes

1975 ◽  
Vol 21 (7) ◽  
pp. 880-883 ◽  
Author(s):  
Francesco Belfiore ◽  
Vito Borzi ◽  
Luigi Lo Vecchio ◽  
Elena Napoli ◽  
Agata M Rabuazzo
Keyword(s):  
Malate Dehydrogenase ◽  
Metabolic Pathways ◽  
Normal Subjects ◽  
Atp Citrate Lyase ◽  
Phosphogluconate Dehydrogenase ◽  
Myelocytic Leukemia ◽  
Citrate Lyase ◽  
Enzymatic Characteristic ◽  
I Cells ◽  
Low Activity

Abstract With respect to the enzymes of NADPH-forming metabolic pathways in human leukocytes: (a) Glucose-6phosphate dehydrogenase and phosphogluconate dehydrogenase (decarboxylating) were less active in leukocytes (mostly myeloblasts) from eight patients with acute myeloblastic leukemia (I) than in leukocytes (mostly granulocytes) from 16 normal subjects (II) or 16 patients with chronic myelocytic leukemia (III). (b) Of the enzymes of the citrate cleavage pathway, ATP citrate lyase and malate dehydrogenase (decarboxylating) (NADP+) were virtually absent in the cells studied. (c) Isocitrate dehydrogenase (NADP+), aspartate aminotransferase, and alanine aminotransferase, which, together with the much more active malate dehydrogenase, constitute a newly proposed NADPH-forming metabolic cycle, showed a higher activity in I than in II or III, and therefore could compensate, as concerns NADPHgeneration, for the low activity of pentose cycle dehydrogenases. We are not sure whether the enzymatic characteristic of I cells is attributable to their immaturity or to their leukemic nature.

scholarly journals Effects of microcompartmentation on flux distribution and metabolic pools in Chlamydomonas reinhardtii chloroplasts

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Anika Küken ◽  
Frederik Sommer ◽  
Liliya Yaneva-Roder ◽  
Luke CM Mackinder ◽  
Melanie Höhne ◽  
...  
Keyword(s):  
Experimental Data ◽  
Chlamydomonas Reinhardtii ◽  
Metabolic Pathways ◽  
Metabolic Flux ◽  
Flux Distribution ◽  
Photosynthetic Performance ◽  
Computational Approach ◽  
Cellular Processes ◽  
Diffusional Barrier ◽  
Computational Strategy

Cells and organelles are not homogeneous but include microcompartments that alter the spatiotemporal characteristics of cellular processes. The effects of microcompartmentation on metabolic pathways are however difficult to study experimentally. The pyrenoid is a microcompartment that is essential for a carbon concentrating mechanism (CCM) that improves the photosynthetic performance of eukaryotic algae. Using Chlamydomonas reinhardtii, we obtained experimental data on photosynthesis, metabolites, and proteins in CCM-induced and CCM-suppressed cells. We then employed a computational strategy to estimate how fluxes through the Calvin-Benson cycle are compartmented between the pyrenoid and the stroma. Our model predicts that ribulose-1,5-bisphosphate (RuBP), the substrate of Rubisco, and 3-phosphoglycerate (3PGA), its product, diffuse in and out of the pyrenoid, respectively, with higher fluxes in CCM-induced cells. It also indicates that there is no major diffusional barrier to metabolic flux between the pyrenoid and stroma. Our computational approach represents a stepping stone to understanding microcompartmentalized CCM in other organisms.

On the Oxidative Metabolism of the Rat Skin during Carcinogenesis induced by 7,12-dimethylbenz[a]anthracene

1966 ◽  
Vol 52 (4) ◽  
pp. 283-293
Author(s):  
Salvatore Di Bella ◽  
Umberto Pinchierri ◽  
Gabriella Richetta
Keyword(s):  
Oxygen Uptake ◽  
Carbohydrate Metabolism ◽  
Dehydrogenase Activity ◽  
Oxidative Metabolism ◽  
Oxidation Rate ◽  
Normal Skin ◽  
Rat Skin ◽  
Phosphogluconate Dehydrogenase ◽  
Normal Rat ◽  
Pathological Tissues

The oxidation rate of citrate, d,1-isocitrate, glucose-6-phosphate and phosphogluconate proceeded two fold more rapidly in slices of rat skin with tumors induced by 7,12-dimethylbenz[a]anthracene than in normal skin. Citrate oxidation was stimulated by addition either of Fe++ or of cysteine, which, when both present in the system, are able to avoid the aconitase inactivation in the tissue. Mn++, NADP, FMN and cytocrome c may activate the oxygen uptake both in normal and pathological tissues, using as substrates respectively citrate, d,1-isocitrate, glucose-6-phosphate or phosphogluconate. The isocitric-dehydrogenase activity of the extracts of tumor induced rat skin resulted lower than that observed in normal rat skin; glucose-6-phosphate and respectively phosphogluconate-dehydrogenase enzymatic levels were two fold higher in the neoplastic than in the normal skin rat extracts. The results presented show an increase of the oxidative carbohydrate metabolism and pentosephosphate shunt, during carcinogenesis in the rat skin.

scholarly journals Untargeted Metabolomics Identifies Key Metabolic Pathways Altered by Thymoquinone in Leukemic Cancer Cells

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1792 ◽  
Author(s):  
Asma Ahmed AlGhamdi ◽  
Mohammed Razeeth Shait Mohammed ◽  
Mazin A. Zamzami ◽  
Abdulrahman L. Al-Malki ◽  
Mohamad Hasan Qari ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Metabolic Pathways ◽  
Nigella Sativa ◽  
Experimental Studies ◽  
Nucleotide Metabolism ◽  
Untargeted Metabolomics ◽  
Sphingolipid Metabolism ◽  
Cancer Cell Survival

Thymoquinone (TQ), a naturally occurring anticancer compound extracted from Nigella sativa oil, has been extensively reported to possess potent anti-cancer properties. Experimental studies showed the anti-proliferative, pro-apoptotic, and anti-metastatic effects of TQ on different cancer cells. One of the possible mechanisms underlying these effects includes alteration in key metabolic pathways that are critical for cancer cell survival. However, an extensive landscape of the metabolites altered by TQ in cancer cells remains elusive. Here, we performed an untargeted metabolomics study using leukemic cancer cell lines during treatment with TQ and found alteration in approximately 335 metabolites. Pathway analysis showed alteration in key metabolic pathways like TCA cycle, amino acid metabolism, sphingolipid metabolism and nucleotide metabolism, which are critical for leukemic cell survival and death. We found a dramatic increase in metabolites like thymine glycol in TQ-treated cancer cells, a metabolite known to induce DNA damage and apoptosis. Similarly, we observed a sharp decline in cellular guanine levels, important for leukemic cancer cell survival. Overall, we provided an extensive metabolic landscape of leukemic cancer cells and identified the key metabolites and pathways altered, which could be critical and responsible for the anti-proliferative function of TQ.

EFFECTS OF TESTOSTERONE PROPIONATE AND CYPROTERONE ACETATE ON CARBOHYDRATE METABOLISM IN RAT MAMMARY GLANDS

1980 ◽  
Vol 84 (3) ◽  
pp. 467-471
Author(s):  
N. DESHPANDE ◽  
IRENE MITCHELL
Keyword(s):  
Carbohydrate Metabolism ◽  
Cyproterone Acetate ◽  
Testosterone Propionate ◽  
Mammary Glands ◽  
Normal Mammary Gland ◽  
Inhibitory Effects ◽  
Phosphogluconate Dehydrogenase ◽  
Normal Rat ◽  
And Function ◽  
Glucose 6 Phosphate Dehydrogenase

The effects of administration of testosterone propionate on the activities of seven of the enzymes of carbohydrate metabolism in normal rat mammary glands were investigated and the validity of the results was confirmed by simultaneous injection of the hormone and cyproterone acetate. The administration of the androgen increased the activities of phosphofructokinase (PFK), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and lactate dehydrogenase (LDH) in glands from both intact and from ovariectomized and adrenalectomized animals. Administration of cyproterone acetate alone resulted in a significant reduction in the activities of PFK and G6PDH and when given together with the androgen it inhibited increases in the activities of PFK, G6PDH, 6PGDH and LDH induced by testosterone. It was concluded that these results did not explain the known inhibitory effects of the androgen on normal mammary gland growth and function.

scholarly journals Modification of Carbohydrate Content in Developing Tomato Fruit

HortScience ◽  
1997 ◽  
Vol 32 (3) ◽  
pp. 551E-551
Author(s):  
Arthur A. Schaffer ◽  
Marina Petreikov ◽  
Daphne Miron ◽  
Miriam Fogelman ◽  
Moshe Spiegelman ◽  
...  
Keyword(s):  
Carbohydrate Metabolism ◽  
Metabolic Pathways ◽  
Tomato Fruit ◽  
Starch Synthesis ◽  
Mature Fruit ◽  
Immature Fruit ◽  
Natural Genetic Variation ◽  
Structural Carbohydrate ◽  
Source Sink ◽  
The Impact

The carbohydrate economy of developing tomato fruit is determined by wholeplant source–sink relationships. However, the fate of the imported photoassimilate partitioned to the fruit sink is controlled by the carbohydrate metabolism of the fruit tissue. Within the Lycopersicon spp. there exists a broad range of genetic variability for fruit carbohydrate metabolism, such as sucrose accumulation and modified ratios of fructose to glucose in the mature fruit and increased starch synthesis in the immature fruit. Metabolic pathways of carbohydrate metabolism in tomatoes, as well as natural genetic variation in the metabolic pathways, will be described. The impact of sink carbohydrate metabolism on fruit non-structural carbohydrate economy will be discussed.

scholarly journals Bifidobacterium breveUCC2003 Employs Multiple Transcriptional Regulators To Control Metabolism of Particular Human Milk Oligosaccharides

2018 ◽  
Vol 84 (9) ◽  
pp. e02774-17 ◽  
Author(s):  
Kieran James ◽  
Mary O'Connell Motherway ◽  
Christophe Penno ◽  
Rebecca Louise O'Brien ◽  
Douwe van Sinderen
Keyword(s):  
Transcriptional Regulation ◽  
Human Milk ◽  
Carbohydrate Metabolism ◽  
Metabolic Pathways ◽  
Transcriptional Regulators ◽  
Prototype Strain ◽  
Regulatory Mechanisms ◽  
Human Milk Oligosaccharides ◽  
Content Type ◽  
Bifidobacterium Breve

ABSTRACTBifidobacterial carbohydrate metabolism has been studied in considerable detail for a variety of both plant- and human-derived glycans, particularly involving the bifidobacterial prototype strainBifidobacterium breveUCC2003. We recently elucidated the metabolic pathways by which thehumanmilkoligosaccharide (HMO) constituents lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT) and lacto-N-biose (LNB) are utilized byB. breveUCC2003. However, to date, no work has been carried out on the regulatory mechanisms that control the expression of the genetic loci involved in these HMO metabolic pathways. In this study, we describe the characterization of three transcriptional regulators and the corresponding operator and associated (inducible) promoter sequences, with the latter governing the transcription of the genetic elements involved in LN(n)T/LNB metabolism. The activity of these regulators is dependent on the release of specific monosaccharides, which are believed to act as allosteric effectors and which are derived from the corresponding HMOs targeted by the particular locus.IMPORTANCEHuman milk oligosaccharides (HMOs) are a key factor in the development of the breastfed-infant microbiota. They function as prebiotics, selecting for a specific range of microbes, including a number of infant-associated species of bifidobacteria, which are thought to provide a range of health benefits to the infant host. While much research has been carried out on elucidating the mechanisms of HMO metabolism in infant-associated bifidobacteria, to date there is very little understanding of the transcriptional regulation of these pathways. This study reveals a multicomponent transcriptional regulation system that controls the recently identified pathways of HMO metabolism in the infant-associatedBifidobacterium breveprototype strain UCC2003. This not only provides insight into the regulatory mechanisms present in other infant-associated bifidobacteria but also provides an example of a network of sequential steps regulating microbial carbohydrate metabolism.

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