scholarly journals BIOSINTESA FOLAT OLEH BAKTERI ASAM LAKTAT

2019 ◽  
Vol 1 (1) ◽  
pp. 11-18
Author(s):  
Siti Nur Purwandhani
Keyword(s):  
Mammalian Cells ◽  
Shikimate Pathway ◽  
Aromatic Amino Acids ◽  
Pentose Phosphate ◽  
Biosynthesis Pathway ◽  
Aminobenzoic Acid ◽  
Dna And Rna ◽  
Folate Biosynthesis ◽  
Rna Biosynthesis ◽  
Micro Organisms

Folate, an important B-group vitamin, participates in many metabolic pathways such as DNA and RNA biosynthesis and amino acid inter-conversions. Mammalian cells cannot synthesize folate; therefore, an exogenous supply of this vitamin is necessary to prevent nutritional deficiency. Folic acid is a composite molecule, being made up of three parts: a pteridine ring system (6-methylpterin), para-aminobenzoic acid , and glutamic acid . The folate biosynthesis pathway in micro-organisms can be divided in several parts. The pteridine proportion of folate is made from GTP, that is synthesized in the purine biosynthesis pathway. p-Aminobenzoic acid originates from chorismate and can be synthesized via the same biosynthesis pathways required for the aromatic amino acids, involving glycolysis, pentose phosphate pathway and shikimate pathway. The third component of a folate molecule is glutamate, that is normally taken up from the medium. This review will focus on biosynthesis and folate production by lactic acid bacteria and the folate level production in fermented product.

scholarly journals Metabolic dependency of chorismate in Plasmodium falciparum suggests an alternative source for the ubiquinone biosynthesis precursor

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ana Lisa Valenciano ◽  
Maria L. Fernández-Murga ◽  
Emilio F. Merino ◽  
Nicole R. Holderman ◽  
Grant J. Butschek ◽  
...  
Keyword(s):  
Malaria Parasite ◽  
Shikimate Pathway ◽  
Aromatic Amino Acids ◽  
Defined Medium ◽  
Current Evidence ◽  
Head Group ◽  
Main Role ◽  
Alternative Source ◽  
Folate Biosynthesis

Abstract The shikimate pathway, a metabolic pathway absent in humans, is responsible for the production of chorismate, a branch point metabolite. In the malaria parasite, chorismate is postulated to be a direct precursor in the synthesis of p-aminobenzoic acid (folate biosynthesis), p-hydroxybenzoic acid (ubiquinone biosynthesis), menaquinone, and aromatic amino acids. While the potential value of the shikimate pathway as a drug target is debatable, the metabolic dependency of chorismate in P. falciparum remains unclear. Current evidence suggests that the main role of chorismate is folate biosynthesis despite ubiquinone biosynthesis being active and essential in the malaria parasite. Our goal in the present work was to expand our knowledge of the ubiquinone head group biosynthesis and its potential metabolic dependency on chorismate in P. falciparum. We systematically assessed the development of both asexual and sexual stages of P. falciparum in a defined medium in the absence of an exogenous supply of chorismate end-products and present biochemical evidence suggesting that the benzoquinone ring of ubiquinones in this parasite may be synthesized through a yet unidentified route.

The Shikimate Pathway: Biosynthesis of Phenolic Products from Shikimic Acid

2016 ◽  
Author(s):  
Gary W. Morrow
Keyword(s):  
Amino Acids ◽  
Secondary Metabolites ◽  
Shikimic Acid ◽  
Shikimate Pathway ◽  
Aromatic Amino Acids ◽  
Essential Amino Acids ◽  
Bimolecular Reaction ◽  
Pentose Phosphate ◽  
Chemotherapy Agent ◽  
Acid Pathway

Like other amino acids, the aromatic amino acids phenylalanine, tyrosine, and tryptophan are vitally important for protein synthesis in all organisms. However, while animals can synthesize tyrosine via oxidation of phenylalanine, they can synthesize neither phenylalanine itself nor tryptophan and so these essential amino acids must be obtained in the diet, usually from plant material. Though many other investigators made significant contributions in this area over the years, it was Bernhard Davis in the early 1950s whose use of mutant stains of Escherichia coli led to a full understanding of the so-called shikimic acid pathway that is used by plants and also by some microorganisms for the biosynthesis of these essential amino acids. The pathway is almost completely devoted to their synthesis for protein production in bacteria, while in plants the pathway extends their use to the construction of a wide array of secondary metabolites, many of which are valuable medicinal agents. These secondary metabolites range from simple and familiar compounds such as vanillin (vanilla flavor and fragrance) and eugenol (oil of clove, a useful dental anesthetic) to more complex structures such as pinoresinol, a common plant biochemical, and podophyllotoxin, a powerful cancer chemotherapy agent. Earlier in Chapter 3, we encountered two important intermediates, erythrose-4-phosphate and phosphoenolpyruvate (PEP), each of which was derived from a different pathway utilized in carbohydrate metabolism. Erythrose-4-P was an intermediate in one of the steps of the pentose phosphate pathway while hydrolysis of PEP to pyruvic acid was the final step in glycolysis. These two simple intermediates provide the seven carbon atoms required for construction of shikimic acid itself. The two are linked to one another via a sequence of enzyme-mediated aldol-type reactions, the first being a bimolecular reaction and the second an intramolecular variant that ultimately leads to a cyclic precursor of shikimic acid known as 3-dehydroquinic acid as shown in Fig. 6.3. Subsequent dehydration of 3-dehydroquinic acid leads to 3-dehydroshikimic acid which then leads directly to shikimic acid via NADPH reduction.

scholarly journals Metabolic dependency of chorismate in Plasmodium falciparum

2019 ◽  
Author(s):  
Ana Lisa Valenciano ◽  
Maria L. Fernández-Murga ◽  
Emilio F. Merino ◽  
Nicole R. Holderman ◽  
Grant J. Butschek ◽  
...  
Keyword(s):  
Malaria Parasite ◽  
Shikimate Pathway ◽  
Aromatic Amino Acids ◽  
Defined Medium ◽  
Current Evidence ◽  
Head Group ◽  
Main Role ◽  
Folate Biosynthesis ◽  
Sexual Stages

The shikimate pathway, a metabolic pathway absent in humans, is responsible for the production of chorismate, a branch point metabolite. In the malaria parasite, chorismate is postulated to be a direct precursor in the synthesis of p-aminobenzoic acid (folate biosynthesis), p-hydroxybenzoic acid (ubiquinone biosynthesis), menaquinone, and aromatic amino acids. While the potential value of the shikimate pathway as a drug target is debatable, the metabolic dependency of chorismate in P. falciparum remains unclear. Current evidence suggests that the main role of chorismate is folate biosynthesis despite ubiquinone biosynthesis being active and essential in the malaria parasite. Our goal in the present work was to expand our knowledge of the ubiquinone head group biosynthesis and its potential metabolic dependency on chorismate in P. falciparum. These data led us to further characterize the mechanism of action of MMV688345, a compound from the open-access “Pathogen Box” collection from Medicine for Malaria Venture. We systematically assessed the development of both asexual and sexual stages of P. falciparum in a defined medium in the absence of an exogenous supply of chorismate end-products and present biochemical evidence suggesting that the benzoquinone ring of ubiquinones in this parasite may be synthesized through a yet unidentified route.

scholarly journals Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ratnasekhar Ch ◽  
Guillaume Rey ◽  
Sandipan Ray ◽  
Pawan K. Jha ◽  
Paul C. Driscoll ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Mammalian Cells ◽  
Metabolic Flux ◽  
Pentose Phosphate ◽  
Human Red Blood Cells ◽  
Integral Process ◽  
Metabolic Oscillations ◽  
Human Rbcs

AbstractCircadian clocks coordinate mammalian behavior and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.

scholarly journals Nucleoside Analogues Are Potent Inducers of Pol V-mediated Mutagenesis

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 843
Author(s):  
Balagra Kasim Sumabe ◽  
Synnøve Brandt Ræder ◽  
Lisa Marie Røst ◽  
Animesh Sharma ◽  
Eric S. Donkor ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Mutation Frequency ◽  
Nucleoside Analogues ◽  
Cancer Therapies ◽  
E Coli ◽  
Replicative Stress ◽  
Pol V ◽  
Dna And Rna ◽  
Sos Induction ◽  
Anti Cancer

Drugs targeting DNA and RNA in mammalian cells or viruses can also affect bacteria present in the host and thereby induce the bacterial SOS system. This has the potential to increase mutagenesis and the development of antimicrobial resistance (AMR). Here, we have examined nucleoside analogues (NAs) commonly used in anti-viral and anti-cancer therapies for potential effects on mutagenesis in Escherichia coli, using the rifampicin mutagenicity assay. To further explore the mode of action of the NAs, we applied E. coli deletion mutants, a peptide inhibiting Pol V (APIM-peptide) and metabolome and proteome analyses. Five out of the thirteen NAs examined, including three nucleoside reverse transcriptase inhibitors (NRTIs) and two anti-cancer drugs, increased the mutation frequency in E. coli by more than 25-fold at doses that were within reported plasma concentration range (Pl.CR), but that did not affect bacterial growth. We show that the SOS response is induced and that the increase in mutation frequency is mediated by the TLS polymerase Pol V. Quantitative mass spectrometry-based metabolite profiling did not reveal large changes in nucleoside phosphate or other central carbon metabolite pools, which suggests that the SOS induction is an effect of increased replicative stress. Our results suggest that NAs/NRTIs can contribute to the development of AMR and that drugs inhibiting Pol V can reverse this mutagenesis.

scholarly journals Poly-L-ornithine-mediated transformation of mammalian cells.

1987 ◽  
Vol 7 (6) ◽  
pp. 2286-2293 ◽  
Author(s):  
V C Bond ◽  
B Wold
Keyword(s):  
Cell Lines ◽  
Mammalian Cells ◽  
High Efficiency ◽  
Protein Product ◽  
Marker Genes ◽  
Recipient Mouse ◽  
L Cells ◽  
Dna And Rna ◽  
Selectable Marker Genes

Poly-L-ornithine has been used to introduce DNA and RNA into mammalian cells in culture. Ornithine-mediated DNA transfer has several interesting and potentially useful properties. The procedure is technically straightforward and is easily applied to either small or large numbers of recipient cells. The efficiency of transformation is high. Under optimal conditions, 1 to 2% of recipient mouse L cells take up and continue to express selectable marker genes. DNA content of transformants can be varied reproducibly, yielding cells with just one or two copies of the new gene under one set of conditions, while under a different set of conditions 25 to 50 copies are acquired. Cotransformation and expression of physically unlinked genes occur at high efficiency under conditions favoring multiple-copy transfer. Polyornithine promotes gene transfer into cell lines other than L cells. These include Friend erythroleukemia cells and NIH 3T3 cells. Both are transformed about 1 order of magnitude more efficiently by this procedure than by standard calcium phosphate products. However, the method does not abolish the large transformation efficiency differences between these cell lines that have been observed previously by other techniques. (vi) mRNA synthesized in vitro was also introduced into cells by this method. The RNA was translated resulting in a transient accumulation of the protein product.

scholarly journals Characterization of the Role of para-Aminobenzoic Acid Biosynthesis in Folate Production by Lactococcus lactis

2007 ◽  
Vol 73 (8) ◽  
pp. 2673-2681 ◽  
Author(s):  
Arno Wegkamp ◽  
Wietske van Oorschot ◽  
Willem M. de Vos ◽  
Eddy J. Smid
Keyword(s):  
Gene Cluster ◽  
Lactococcus Lactis ◽  
Gene Clusters ◽  
Defined Medium ◽  
Biosynthesis Pathway ◽  
Chemically Defined Medium ◽  
Aminobenzoic Acid ◽  
Biosynthesis Gene Cluster ◽  
Gene Coding ◽  
Aba Biosynthesis

ABSTRACT The pab genes for para-aminobenzoic acid (pABA) biosynthesis in Lactococcus lactis were identified and characterized. In L. lactis NZ9000, only two of the three genes needed for pABA production were initially found. No gene coding for 4-amino-4-deoxychorismate lyase (pabC) was initially annotated, but detailed analysis revealed that pabC was fused with the 3′ end of the gene coding for chorismate synthetase component II (pabB). Therefore, we hypothesize that all three enzyme activities needed for pABA production are present in L. lactis, allowing for the production of pABA. Indeed, the overexpression of the pABA gene cluster in L. lactis resulted in elevated pABA pools, demonstrating that the genes are involved in the biosynthesis of pABA. Moreover, a pABA knockout (KO) strain lacking pabA and pabB C was constructed and shown to be unable to produce folate when cultivated in the absence of pABA. This KO strain was unable to grow in chemically defined medium lacking glycine, serine, nucleobases/nucleosides, and pABA. The addition of the purine guanine, adenine, xanthine, or inosine restored growth but not the production of folate. This suggests that, in the presence of purines, folate is not essential for the growth of L. lactis. It also shows that folate is not strictly required for the pyrimidine biosynthesis pathway. L. lactis strain NZ7024, overexpressing both the folate and pABA gene clusters, was found to produce 2.7 mg of folate/liter per optical density unit at 600 nm when the strain was grown on chemically defined medium without pABA. This is in sharp contrast to L. lactis strains overexpressing only one of the two gene clusters. Therefore, we conclude that elevated folate levels can be obtained only by the overexpression of folate combined with the overexpression of the pABA biosynthesis gene cluster, suggesting the need for a balanced carbon flux through the folate and pABA biosynthesis pathway in the wild-type strain.

NonO, a non-POU-domain-containing, octamer-binding protein, is the mammalian homolog of Drosophila nonAdiss

1993 ◽  
Vol 13 (9) ◽  
pp. 5593-5603
Author(s):  
Y S Yang ◽  
J H Hanke ◽  
L Carayannopoulos ◽  
C M Craft ◽  
J D Capra ◽  
...  
Keyword(s):  
Amino Acids ◽  
Dna Binding ◽  
Protein Binding ◽  
Aromatic Amino Acids ◽  
Courtship Song ◽  
Dna Binding Domain ◽  
Binding Motifs ◽  
Dna And Rna ◽  
Pou Domain ◽  
A Site

We have cloned the ubiquitous form of an octamer-binding, 60-kDa protein (NonO) that appears to be the mammalian equivalent of the Drosophila visual and courtship song behavior protein, no-on-transient A/dissonance (nonAdiss). A region unprecedently rich in aromatic amino acids containing two ribonuclear protein binding motifs is highly conserved between the two proteins. A ubiquitous form of NonO is present in all adult tissues, whereas lymphocytes and retina express unique forms of NonO mRNA. The ubiquitous form contains a potential helix-turn-helix motif followed by a highly charged region but differs from prototypic octamer-binding factors by lacking the POU DNA-binding domain. In addition to its conventional octamer duplex-binding, NonO binds single-stranded DNA and RNA at a site independent of the duplex site.

scholarly journals Adaptation of bacteria to glyphosate: a microevolutionary perspective of the enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase

2020 ◽  
Author(s):  
Miia J. Rainio ◽  
Suvi Ruuskanen ◽  
Marjo Helander ◽  
Kari Saikkonen ◽  
Irma Saloniemi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Active Site ◽  
Shikimate Pathway ◽  
Aromatic Amino Acids ◽  
Ecosystem Functions ◽  
Epsp Synthase

ABSTRACTGlyphosate is the leading herbicide worldwide, but it also affects prokaryotes because it targets the central enzyme (EPSPS) of the shikimate pathway in the synthesis of the three essential aromatic amino acids in autotrophs. Our results reveal that bacteria easily become resistant to glyphosate through changes in the EPSPS active site. This indicates the importance of examining how glyphosate affects microbe-mediated ecosystem functions and human microbiomes.

scholarly journals BIOLOGICAL ACTIVITY OF YERSINIA PSEUDOTUBERCULOSIS TOXINS

2016 ◽  
pp. 10-19
Author(s):  
N. A. Terentieva ◽  
N. F. Timchenko ◽  
V. A. Golotin ◽  
V. A. Rasskazov
Keyword(s):  
Nucleic Acids ◽  
Sea Urchin ◽  
Yersinia Pseudotuberculosis ◽  
Protein Biosynthesis ◽  
Sea Urchin Embryos ◽  
Dna And Rna ◽  
Embryo Cells ◽  
Protein Toxins ◽  
Rna Biosynthesis ◽  
High Concentrations

Aim. Study of effect of heat-labile (HLT) and thermostable (HST) lethal toxins of Yersinia pseudotuberculosis on the development of embryos of sea urchin Strongylocentrotus intermedius, processes of biosynthesis of nucleic acids and protein in embryo cells and activity of nucleoside-kinases of sea urchin. Materials and methods. Y. pseudotuberculosis strains 2517 (pYV-) and 512 (pYV48MD, pYV82MD) were used for isolation of HLT and HST. Gametes and embryos of sea urchin S. intermedius were used to carry out the experiments and isolate nucleoside-kinases. Results. Both of the studied toxins of Y. pseudotuberculosis possessed spermiotoxic effect and reduced fertilizing ability of sea urchin spermies. HLT LD50 was 1 (ig/ml, and HST - 2 pg/ml. Toxins affected the development of embryos of sea urchin resulting in severe morphologic damages, cessation of the development of embryos at early stages of embryogenesis, destruction of cells and death of embryos. Wherein, damaging effect of HLT was observed at lower concentrations compared with HST. HLT inhibited DNA and RNA biosynthesis at concentrations of 1-2 pg/ml. HST did not affect biosynthesis of nucleic acids even at high concentrations, but inhibited protein biosynthesis in sea urchin embryos. HLT did not reduce the level of inclusion of labeled amino acids into embryo cells. HLT had inhibiting effect on the activity of thymidine- and uridine-kinase of sea urchin, whereas HST did not affect these enzymes. Conclusion. Both of Y. pseudotuberculosis protein toxins affect the development of sea urchin embryos, however, mechanisms of action of HLT and HST on embryos and processes occurring in them differ.

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