The pentose phosphate pathway in the endoplasmic reticulum.

Abstract Hexose-6-phosphate dehydrogenase (H6PD) is a luminal enzyme of the endoplasmic reticulum that is distinguished from cytosolic glucose-6-phosphate dehydrogenase by several features. H6PD converts glucose-6-phosphate and NADP+ to 6-phosphogluconate and NADPH, thereby catalyzing the first two reactions of the pentose-phosphate pathway. Because the endoplasmic reticulum has a separate pyridine nucleotide pool, H6PD provides NADPH for luminal reductases. One of these enzymes, 11β-hydroxysteroid dehydrogenase type 1 responsible for prereceptorial activation of glucocorticoids, has been the focus of much attention as a probable factor in the pathomechanism of several human diseases including insulin resistance and the metabolic syndrome. This review summarizes recent advances related to the functions of H6PD.

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NADPH Production by the Pentose Phosphate Pathway in the Zona Fasciculata of Rat Adrenal Gland

Journal of Histochemistry & Cytochemistry ◽

10.1369/jhc.7a7222.2007 ◽

2007 ◽

Vol 55 (9) ◽

pp. 975-980 ◽

Cited By ~ 17

Author(s):

Wilma M. Frederiks ◽

Intan P.E.D. Kümmerlin ◽

Klazina S. Bosch ◽

Heleen Vreeling-Sindelárová ◽

Ard Jonker ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Adrenal Gland ◽

Steroid Hormones ◽

Pentose Phosphate Pathway ◽

Smooth Endoplasmic Reticulum ◽

Feedback Regulation ◽

Pentose Phosphate ◽

G6pd Activity ◽

Zona Fasciculata ◽

Glucose 6 Phosphate Dehydrogenase

Biosynthesis of steroid hormones in the cortex of the adrenal gland takes place in smooth endoplasmic reticulum and mitochondria and requires NADPH. Four enzymes produce NADPH: glucose-6-phosphate dehydrogenase (G6PD), the key regulatory enzyme of the pentose phosphate pathway, phosphogluconate dehydrogenase (PGD), the third enzyme of that pathway, malate dehydrogenase (MDH), and isocitrate dehydrogenase (ICDH). However, the contribution of each enzyme to NADPH production in the cortex of adrenal gland has not been established. Therefore, activity of G6PD, PGD, MDH, and ICDH was localized and quantified in rat adrenocortical tissue using metabolic mapping, image analysis, and electron microscopy. The four enzymes have similar localization patterns in adrenal gland with highest activities in the zona fasciculata of the cortex. G6PD activity was strongest, PGD, MDH, and ICDH activity was ∼60%, 15%, and 7% of G6PD activity, respectively. The Km value of G6PD for glucose-6-phosphate was two times higher than the Km value of PGD for phosphogluconate. As a consequence, virtual flux rates through G6PD and PGD are largely similar. It is concluded that G6PD and PGD provide the major part of NADPH in adrenocortical cells. Their activity is localized in the cytoplasm associated with free ribosomes and membranes of the smooth endoplasmic reticulum, indicating that NADPH-demanding processes related to biosynthesis of steroid hormones take place at these sites. Complete inhibition of G6PD by androsterones suggests that there is feedback regulation of steroid hormone biosynthesis via G6PD.

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Faculty Opinions recommendation of Convergent evolution of zoonotic Brucella species toward the selective use of the pentose phosphate pathway.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738798441.793579509 ◽

2020 ◽

Author(s):

Jean Celli

Keyword(s):

Pentose Phosphate Pathway ◽

Convergent Evolution ◽

Pentose Phosphate ◽

Brucella Species

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Systematic Identification of Regulators of Oxidative Stress Reveals Non-canonical Roles for Peroxisomal Import and the Pentose Phosphate Pathway

Cell Reports ◽

10.1016/j.celrep.2020.01.013 ◽

2020 ◽

Vol 30 (5) ◽

pp. 1417-1433.e7 ◽

Cited By ~ 7

Author(s):

Michael M. Dubreuil ◽

David W. Morgens ◽

Kanji Okumoto ◽

Masanori Honsho ◽

Kévin Contrepois ◽

...

Keyword(s):

Oxidative Stress ◽

Pentose Phosphate Pathway ◽

Pentose Phosphate ◽

Systematic Identification

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Resolving the TCA cycle and pentose-phosphate pathway of Clostridium acetobutylicum ATCC 824: Isotopomer analysis, in vitro activities and expression analysis

Biotechnology Journal ◽

10.1002/biot.201000282 ◽

2010 ◽

Vol 6 (3) ◽

pp. 300-305 ◽

Cited By ~ 69

Author(s):

Scott B. Crown ◽

Dinesh C. Indurthi ◽

Woo Suk Ahn ◽

Jungik Choi ◽

Eleftherios T. Papoutsakis ◽

...

Keyword(s):

Expression Analysis ◽

Pentose Phosphate Pathway ◽

Clostridium Acetobutylicum ◽

Tca Cycle ◽

Pentose Phosphate ◽

The Tca Cycle ◽

Isotopomer Analysis ◽

Clostridium Acetobutylicum Atcc 824

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Geranylgeranylacetone attenuates cerebral ischemia–reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study

BMC Neuroscience ◽

10.1186/s12868-021-00614-7 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Kazuya Matsuo ◽

Kohkichi Hosoda ◽

Jun Tanaka ◽

Yusuke Yamamoto ◽

Taichiro Imahori ◽

...

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Pentose Phosphate Pathway ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Pentose Phosphate ◽

Cerebral Ischemia Reperfusion ◽

Hsp27 Phosphorylation ◽

Cerebral Ischemia Reperfusion Injury ◽

Preliminary Study

Abstract Background We previously reported that heat shock protein 27 (HSP27) phosphorylation plays an important role in the activation of glucose-6-phosphate dehydrogenase (G6PD), resulting in the upregulation of the pentose phosphate pathway and antioxidant effects against cerebral ischemia–reperfusion injury. The present study investigated the effect of geranylgeranylacetone, an inducer of HSP27, on ischemia–reperfusion injury in male rats as a preliminary study to see if further research of the effects of geranylgeranylacetone on the ischemic stroke was warranted. Methods In all experiments, male Wistar rats were used. First, we conducted pathway activity profiling based on a gas chromatography–mass spectrometry to identify ischemia–reperfusion-related metabolic pathways. Next, we investigated the effects of geranylgeranylacetone on the pentose phosphate pathway and ischemia–reperfusion injury by real-time polymerase chain reaction (RT-PCR), immunoblotting, and G6PD activity, protein carbonylation and infarct volume analysis. Geranylgeranylacetone or vehicle was injected intracerebroventricularly 3 h prior to middle cerebral artery occlusion or sham operation. Results Pathway activity profiling demonstrated that changes in the metabolic state depended on reperfusion time and that the pentose phosphate pathway and taurine-hypotaurine metabolism pathway were the most strongly related to reperfusion among 137 metabolic pathways. RT-PCR demonstrated that geranylgeranylacetone did not significantly affect the increase in HSP27 transcript levels after ischemia–reperfusion. Immunoblotting showed that geranylgeranylacetone did not significantly affect the elevation of HSP27 protein levels. However, geranylgeranylacetone significantly increase the elevation of phosphorylation of HSP27 after ischemia–reperfusion. In addition, geranylgeranylacetone significantly affected the increase in G6PD activity, and reduced the increase in protein carbonylation after ischemia–reperfusion. Accordingly, geranylgeranylacetone significantly reduced the infarct size (median 31.3% vs 19.9%, p = 0.0013). Conclusions As a preliminary study, these findings suggest that geranylgeranylacetone may be a promising agent for the treatment of ischemic stroke and would be worthy of further study. Further studies are required to clearly delineate the mechanism of geranylgeranylacetone-induced HSP27 phosphorylation in antioxidant effects, which may guide the development of new approaches for minimizing the impact of cerebral ischemia–reperfusion injury.

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Pentose Phosphate Pathway Reactions in Photosynthesizing Cells

Cells ◽

10.3390/cells10061547 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1547

Author(s):

Thomas D. Sharkey

Keyword(s):

Pentose Phosphate Pathway ◽

Strong Association ◽

Pentose Phosphate ◽

Critical Component ◽

Reaction Sequence ◽

Response To Stress ◽

Labeling Pattern

The pentose phosphate pathway (PPP) is divided into an oxidative branch that makes pentose phosphates and a non-oxidative branch that consumes pentose phosphates, though the non-oxidative branch is considered reversible. A modified version of the non-oxidative branch is a critical component of the Calvin–Benson cycle that converts CO2 into sugar. The reaction sequence in the Calvin–Benson cycle is from triose phosphates to pentose phosphates, the opposite of the typical direction of the non-oxidative PPP. The photosynthetic direction is favored by replacing the transaldolase step of the normal non-oxidative PPP with a second aldolase reaction plus sedoheptulose-1,7-bisphosphatase. This can be considered an anabolic version of the non-oxidative PPP and is found in a few situations other than photosynthesis. In addition to the strong association of the non-oxidative PPP with photosynthesis metabolism, there is recent evidence that the oxidative PPP reactions are also important in photosynthesizing cells. These reactions can form a shunt around the non-oxidative PPP section of the Calvin–Benson cycle, consuming three ATP per glucose 6-phosphate consumed. A constitutive operation of this shunt occurs in the cytosol and gives rise to an unusual labeling pattern of photosynthetic metabolites while an inducible shunt in the stroma may occur in response to stress.

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Fine tuning the glycolytic flux ratio of EP-bifido pathway for mevalonate production by enhancing glucose-6-phosphate dehydrogenase (Zwf) and CRISPRi suppressing 6-phosphofructose kinase (PfkA) in Escherichia coli

Microbial Cell Factories ◽

10.1186/s12934-021-01526-1 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Ying Li ◽

He Xian ◽

Ya Xu ◽

Yuan Zhu ◽

Zhijie Sun ◽

...

Keyword(s):

Pentose Phosphate Pathway ◽

Conversion Rate ◽

Metabolic Flux ◽

Flux Ratio ◽

Reducing Power ◽

Pentose Phosphate ◽

Fine Tuning ◽

High Yield ◽

Glycolytic Flux ◽

Acetyl Coa

Abstract Background Natural glycolysis encounters the decarboxylation of glucose partial oxidation product pyruvate into acetyl-CoA, where one-third of the carbon is lost at CO2. We previously constructed a carbon saving pathway, EP-bifido pathway by combining Embden-Meyerhof-Parnas Pathway, Pentose Phosphate Pathway and “bifid shunt”, to generate high yield acetyl-CoA from glucose. However, the carbon conversion rate and reducing power of this pathway was not optimal, the flux ratio of EMP pathway and pentose phosphate pathway (PPP) needs to be precisely and dynamically adjusted to improve the production of mevalonate (MVA). Result Here, we finely tuned the glycolytic flux ratio in two ways. First, we enhanced PPP flux for NADPH supply by replacing the promoter of zwf on the genome with a set of different strength promoters. Compared with the previous EP-bifido strains, the zwf-modified strains showed obvious differences in NADPH, NADH, and ATP synthesis levels. Among them, strain BP10BF accumulated 11.2 g/L of MVA after 72 h of fermentation and the molar conversion rate from glucose reached 62.2%. Second, pfkA was finely down-regulated by the clustered regularly interspaced short palindromic repeats interference (CRISPRi) system. The MVA yield of the regulated strain BiB1F was 8.53 g/L, and the conversion rate from glucose reached 68.7%. Conclusion This is the highest MVA conversion rate reported in shaken flask fermentation. The CRISPRi and promoter fine-tuning provided an effective strategy for metabolic flux redistribution in many metabolic pathways and promotes the chemicals production.

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