scholarly journals The plastidial pentose phosphate pathway is essential for postglobular embryo development in Arabidopsis

2019 ◽  
Vol 116 (30) ◽  
pp. 15297-15306 ◽  
Author(s):  
Vasilios M. E. Andriotis ◽  
Alison M. Smith
Keyword(s):  
Embryo Development ◽  
Pentose Phosphate Pathway ◽  
Aromatic Amino Acids ◽  
Endosperm Development ◽  
Pentose Phosphate ◽  
Purine Nucleotide ◽  
Purine Nucleotides ◽  
Nucleotide Biosynthesis ◽  
Stage Of Development ◽  
Globular Stage

Large numbers of genes essential for embryogenesis in Arabidopsis encode enzymes of plastidial metabolism. Disruption of many of these genes results in embryo arrest at the globular stage of development. However, the cause of lethality is obscure. We examined the role of the plastidial oxidative pentose phosphate pathway (OPPP) in embryo development. In nonphotosynthetic plastids the OPPP produces reductant and metabolic intermediates for central biosynthetic processes. Embryos with defects in various steps in the oxidative part of the OPPP had cell division defects and arrested at the globular stage, revealing an absolute requirement for the production via these steps of ribulose-5-phosphate. In the nonoxidative part of the OPPP, ribulose-5-phosphate is converted to ribose-5-phosphate (R5P)—required for purine nucleotide and histidine synthesis—and subsequently to erythrose-4-phosphate, which is required for synthesis of aromatic amino acids. We show that embryo development through the globular stage specifically requires synthesis of R5P rather than erythrose-4-phosphate. Either a failure to convert ribulose-5-phosphate to R5P or a block in purine nucleotide biosynthesis beyond R5P perturbs normal patterning of the embryo, disrupts endosperm development, and causes early developmental arrest. We suggest that seed abortion in mutants unable to synthesize R5P via the oxidative part of the OPPP stems from a lack of substrate for synthesis of purine nucleotides, and hence nucleic acids. Our results show that the plastidial OPPP is essential for normal developmental progression as well as for growth in the embryo.

Regulation of purine nucleotide biosynthesis: in yeast and beyond

2006 ◽  
Vol 34 (5) ◽  
pp. 786-790 ◽  
Author(s):  
R.J. Rolfes
Keyword(s):  
Saccharomyces Cerevisiae ◽  
De Novo ◽  
Purine Nucleotide ◽  
De Novo Synthesis ◽  
Normal Functioning ◽  
Purine Nucleotides ◽  
Yeast Saccharomyces Cerevisiae ◽  
Nucleotide Biosynthesis ◽  
Salvage Pathways ◽  
Pool Sizes

Purine nucleotides are critically important for the normal functioning of cells due to their myriad of activities. It is important for cells to maintain a balance in the pool sizes of the adenine-containing and guanine-containing nucleotides, which occurs by a combination of de novo synthesis and salvage pathways that interconvert the purine nucleotides. This review describes the mechanism for regulation of the biosynthetic genes in the yeast Saccharomyces cerevisiae and compares this mechanism with that described in several microbial species.

scholarly journals Enhanced glucose metabolism through activation of HIF-1α covers the energy demand in a rat embryonic heart primordium after heartbeat initiation

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Tatsuya Sato ◽  
Nobutoshi Ichise ◽  
Takeshi Kobayashi ◽  
Hiroyori Fusagawa ◽  
Hiroya Yamazaki ◽  
...  
Keyword(s):  
Pentose Phosphate Pathway ◽  
Energy Demand ◽  
Glucose Transporter ◽  
Hypoxia Inducible Factor ◽  
Atp Synthesis ◽  
Pentose Phosphate ◽  
Metabolome Analysis ◽  
Nucleotide Biosynthesis ◽  
Metabolic Characteristics ◽  
Before And After

AbstractThe initiation of heartbeat is an essential step in cardiogenesis in the heart primordium, but it remains unclear how intracellular metabolism responds to increased energy demands after heartbeat initiation. In this study, embryos in Wistar rats at embryonic day 10, at which heartbeat begins in rats, were divided into two groups by the heart primordium before and after heartbeat initiation and their metabolic characteristics were assessed. Metabolome analysis revealed that increased levels of ATP, a main product of glucose catabolism, and reduced glutathione, a by-product of the pentose phosphate pathway, were the major determinants in the heart primordium after heartbeat initiation. Glycolytic capacity and ATP synthesis-linked mitochondrial respiration were significantly increased, but subunits in complexes of mitochondrial oxidative phosphorylation were not upregulated in the heart primordium after heartbeat initiation. Hypoxia-inducible factor (HIF)-1α was activated and a glucose transporter and rate-limiting enzymes of the glycolytic and pentose phosphate pathways, which are HIF-1α-downstream targets, were upregulated in the heart primordium after heartbeat initiation. These results suggest that the HIF-1α-mediated enhancement of glycolysis with activation of the pentose phosphate pathway, potentially leading to antioxidant defense and nucleotide biosynthesis, covers the increased energy demand in the beating and developing heart primordium.

scholarly journals The Pentose Phosphate Pathway in Yeasts–More Than a Poor Cousin of Glycolysis

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 725
Author(s):  
Laura-Katharina Bertels ◽  
Lucía Fernández Murillo ◽  
Jürgen J. Heinisch
Keyword(s):  
Pentose Phosphate Pathway ◽  
Kluyveromyces Lactis ◽  
Aromatic Amino Acids ◽  
Pentose Phosphate ◽  
Minor Role ◽  
Disease Genes ◽  
Yeast Saccharomyces Cerevisiae ◽  
Key Enzyme ◽  
A Minor ◽  
Glucose 6 Phosphate Dehydrogenase

The pentose phosphate pathway (PPP) is a route that can work in parallel to glycolysis in glucose degradation in most living cells. It has a unidirectional oxidative part with glucose-6-phosphate dehydrogenase as a key enzyme generating NADPH, and a non-oxidative part involving the reversible transketolase and transaldolase reactions, which interchange PPP metabolites with glycolysis. While the oxidative branch is vital to cope with oxidative stress, the non-oxidative branch provides precursors for the synthesis of nucleic, fatty and aromatic amino acids. For glucose catabolism in the baker’s yeast Saccharomyces cerevisiae, where its components were first discovered and extensively studied, the PPP plays only a minor role. In contrast, PPP and glycolysis contribute almost equally to glucose degradation in other yeasts. We here summarize the data available for the PPP enzymes focusing on S. cerevisiae and Kluyveromyces lactis, and describe the phenotypes of gene deletions and the benefits of their overproduction and modification. Reference to other yeasts and to the importance of the PPP in their biotechnological and medical applications is briefly being included. We propose future studies on the PPP in K. lactis to be of special interest for basic science and as a host for the expression of human disease genes.

scholarly journals Potential Drug Targets in the Pentose Phosphate Pathway of Trypanosomatids

2019 ◽  
Vol 25 (39) ◽  
pp. 5239-5265 ◽  
Author(s):  
Inês Loureiro ◽  
Joana Faria ◽  
Nuno Santarem ◽  
Terry K. Smith ◽  
Joana Tavares ◽  
...  
Keyword(s):  
Pentose Phosphate Pathway ◽  
Drug Targets ◽  
Redox Homeostasis ◽  
Aromatic Amino Acids ◽  
Pentose Phosphate ◽  
New Drugs ◽  
Potential Drug ◽  
Leishmania Spp ◽  
Causative Agents ◽  
Potential Drug Targets

The trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp, are causative agents of important human diseases such as African sleeping sickness, Chagas’ disease and Leishmaniasis, respectively. The high impact of these diseases on human health and economy worldwide, the unsatisfactory available chemotherapeutic options and the absence of human effective vaccines, strongly justifies the search for new drugs. The pentose phosphate pathway has been proposed to be a viable strategy to defeat several infectious diseases, including those from trypanosomatids, as it includes an oxidative branch, important in the maintenance of cell redox homeostasis, and a non-oxidative branch in which ribose 5-phosphate and erythrose 4-phosphate, precursors of nucleic acids and aromatic amino acids, are produced. This review provides an overview of the available chemotherapeutic options against these diseases and discusses the potential of genetically validated enzymes from the pentose phosphate pathway of trypanosomatids to be explored as potential drug targets.

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

Cell Reports ◽  
2020 ◽  
Vol 30 (5) ◽  
pp. 1417-1433.e7 ◽  
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

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

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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