scholarly journals Deciphering the enigmatic role of the amidotransferase LipL inBacillus subtilislipoic acid utilization

2018 ◽  
Author(s):  
Natalí B. Rasetto ◽  
Antonela Lavatelli ◽  
Natalia Martin ◽  
María Cecilia Mansilla
Keyword(s):  
Carbon Metabolism ◽  
Essential Role ◽  
Glycine Cleavage System ◽  
Growth Defects ◽  
Gram Positive Bacteria ◽  
Glycine Cleavage ◽  
One Carbon Metabolism ◽  
Branched Chain ◽  
Octanoyl Group

AbstractLipoate is an essential cofactor for key enzymes of oxidative and one-carbon metabolism. It is covalently attached to E2 subunits of dehydrogenase (DH) complexes and the GcvH subunit of the glycine cleavage system.Bacillus subtilispossess two protein lipoylation pathways: biosynthesis and scavenging. The former requires octanoylation of GcvH, amidotransfer of the octanoate to E2s, and insertion of sulfur atoms. Lipoate scavenging is mediated by a lipoate ligase (LplJ), that catalizes a classical two-step ATP-dependent reaction. Although these pathways were thought to be redundant, a ΔlipLmutant, unable to transfer the octanoyl group from GcvH to the E2s during lipoate synthesis, showed growth defects in minimal media even when supplemented with this cofactor, despite the presence of a functional LplJ. In this study we demonstrated that LipL is essential to modify E2 subunits of branched chain ketoacid and pyruvate DH during lipoate scavenging. LipL must be functional and it is not forming a complex with LplJ, which suggests that these enzymes might be acting sequentially. We also show that the E2 subunit of oxoglutarate DH is a good donor for LipL amidotransfer reaction. The essential role of LipL during lipoate utilization relies on the strict substrate specificity of LplJ, determined by charge complementarity between the ligase and the lipoylable subunits. LplJ does not recognize E2 subunits without a negatively charged residue in key positions of the target protein, and thus LipL is required to transfer the lipoate to them. This model of lipoate scavenging seems widespread among Gram-positive bacteria.

scholarly journals Essential Role of One-carbon Metabolism and Gcn4p and Bas1p Transcriptional Regulators during Adaptation to Anaerobic Growth ofSaccharomyces cerevisiae

2009 ◽  
Vol 284 (17) ◽  
pp. 11205-11215 ◽  
Author(s):  
Bonny M. Tsoi ◽  
Anthony G. Beckhouse ◽  
Cristy L. Gelling ◽  
Mark J. Raftery ◽  
Joyce Chiu ◽  
...  
Keyword(s):  
Carbon Metabolism ◽  
Essential Role ◽  
Transcriptional Regulators ◽  
Anaerobic Growth ◽  
One Carbon Metabolism

Ontogeny of hepatic enzymes involved in serine- and folate-dependent one-carbon metabolism in rabbits

2001 ◽  
Vol 280 (5) ◽  
pp. G873-G878 ◽  
Author(s):  
Henry R. Thompson ◽  
Gayle M. Jones ◽  
Michael R. Narkewicz
Keyword(s):  
Carbon Metabolism ◽  
Specific Activity ◽  
Serine Hydroxymethyltransferase ◽  
Central Position ◽  
Fetal Life ◽  
Glycine Cleavage System ◽  
Hepatic Enzymes ◽  
Methenyltetrahydrofolate Synthetase ◽  
Glycine Cleavage ◽  
One Carbon Metabolism

Serine occupies a central position in folate-dependent, one-carbon metabolism through 5,10-methylenetetrahydrofolate (MTHF) and 5-formyltetrahydrofolate (FTHF). We characterized the ontogeny of the specific activity of key enzymes involved in serine, 5,10-MTHF, and 5-FTHF metabolism: methenyltetrahydrofolate synthetase (MTHFS), MTHF reductase (MTHFR), the glycine cleavage system (GCS), methionine synthase (MS), and serine hydroxymethyltransferase (SHMT) in rabbit liver, placenta, brain, and kidney. In liver, MTHFS activity is low in the fetus (0.36 ± 0.07 nmol · min−1 · mg protein−1), peaks at 3 wk (1.48 ± 0.50 nmol · min−1 · mg protein−1), and then decreases to adult levels (1.13 ± 0.32 nmol · min−1 · mg protein−1). MTHFR activity is highest early in gestation (24.9 ± 2.4 nmol · h−1 · mg protein−1) and declines rapidly by birth (4.7 ± 1.3 nmol · h−1 · mg protein−1). MS is highest during fetal life and declines after birth. Cytosolic SHMT activity does not vary during development, but mitochondrial SHMT peaks at 23 days. GCS activity is high in the fetus and the neonate, declining after weaning. In placenta and brain, all activities are low throughout gestation. Cytosolic and mitochondrial SHMT activities are low in kidney and rise after weaning, whereas MTHFS is low throughout development. These data suggest that the liver is the primary site of activity for these enzymes. Throughout development, there are multiple potential sources for production of 5,10-MTHF, but early in gestation high MTHFR activity and low MTHFS activity could reduce 5,10-MTHF availability.

The role of H-NS in one carbon metabolism

Biochimie ◽  
1994 ◽  
Vol 76 (10-11) ◽  
pp. 1063-1070 ◽  
Author(s):  
J.R. Landgraf ◽  
M. Levinthal ◽  
A. Danchin
Keyword(s):  
Carbon Metabolism ◽  
One Carbon Metabolism

scholarly journals Genomic Insights Into the Lifestyles of Thaumarchaeota Inside Sponges

2021 ◽  
Vol 11 ◽  
Author(s):  
Markus Haber ◽  
Ilia Burgsdorf ◽  
Kim M. Handley ◽  
Maxim Rubin-Blum ◽  
Laura Steindler
Keyword(s):  
The Novel ◽  
Glycine Cleavage System ◽  
Free Living ◽  
High Affinity ◽  
Branched Chain Amino Acid ◽  
Glycine Cleavage ◽  
Microbial Symbionts ◽  
Host Sponge ◽  
Branched Chain ◽  
Sponge Symbionts

Sponges are among the oldest metazoans and their success is partly due to their abundant and diverse microbial symbionts. They are one of the few animals that have Thaumarchaeota symbionts. Here we compare genomes of 11 Thaumarchaeota sponge symbionts, including three new genomes, to free-living ones. Like their free-living counterparts, sponge-associated Thaumarchaeota can oxidize ammonia, fix carbon, and produce several vitamins. Adaptions to life inside the sponge host include enrichment in transposases, toxin-antitoxin systems and restriction modifications systems, enrichments previously reported also from bacterial sponge symbionts. Most thaumarchaeal sponge symbionts lost the ability to synthesize rhamnose, which likely alters their cell surface and allows them to evade digestion by the host. All but one archaeal sponge symbiont encoded a high-affinity, branched-chain amino acid transporter system that was absent from the analyzed free-living thaumarchaeota suggesting a mixotrophic lifestyle for the sponge symbionts. Most of the other unique features found in sponge-associated Thaumarchaeota, were limited to only a few specific symbionts. These features included the presence of exopolyphosphatases and a glycine cleavage system found in the novel genomes. Thaumarchaeota have thus likely highly specific interactions with their sponge host, which is supported by the limited number of host sponge species to which each of these symbionts is restricted.

The role of one-carbon metabolism and homocysteine in Parkinson’s disease onset, pathology and mechanisms

2019 ◽  
Vol 32 (2) ◽  
pp. 218-230 ◽  
Author(s):  
Lauren K. Murray ◽  
Nafisa M. Jadavji
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Carbon Metabolism ◽  
Animal Studies ◽  
B Vitamins ◽  
Present Review ◽  
Increased Risk ◽  
One Carbon Metabolism ◽  
B Vitamin

AbstractParkinson’s disease (PD) is the second most common neurodegenerative disorder. It is characterised by the progressive degeneration of dopaminergic (DA) neurons. The cause of degeneration is not well understood; however, both genetics and environmental factors, such as nutrition, have been implicated in the disease process. Deficiencies in one-carbon metabolism in particular have been associated with increased risk for PD onset and progression, though the precise relationship is unclear. The aim of the present review is to determine the role of one-carbon metabolism and elevated levels of homocysteine in PD onset and pathology and to identify potential mechanisms involved. A search of PubMed, Google Scholar and Web of Science was undertaken to identify relevant human and animal studies. Case–control, prospective cohort studies, meta-analyses and non-randomised trials were included in the present review. The results from human studies indicate that polymorphisms in one-carbon metabolism may increase risk for PD development. There is an unclear role for dietary B-vitamin intake on PD onset and progression. However, dietary supplementation with B-vitamins may be beneficial for PD-affected individuals, particularly those on l-DOPA (levodopa or l-3,4-dihydroxyphenylalanine) treatment. Additionally, one-carbon metabolism generates methyl groups, and methylation capacity in PD-affected individuals is reduced. This reduced capacity has an impact on expression of disease-specific genes that may be involved in PD progression. During B-vitamin deficiency, animal studies report increased vulnerability of DA cells through increased oxidative stress and altered methylation. Nutrition, especially folates and related B-vitamins, may contribute to the onset and progression of PD by making the brain more vulnerable to damage; however, further investigation is required.

scholarly journals Mutations of the Listeria monocytogenes PeptidoglycanN-Deacetylase andO-Acetylase Result in Enhanced Lysozyme Sensitivity, Bacteriolysis, and Hyperinduction of Innate Immune Pathways

2011 ◽  
Vol 79 (9) ◽  
pp. 3596-3606 ◽  
Author(s):  
Chris S. Rae ◽  
Aimee Geissler ◽  
Paul C. Adamson ◽  
Daniel A. Portnoy
Keyword(s):  
Listeria Monocytogenes ◽  
Transcriptional Responses ◽  
Gram Positive ◽  
Content Type ◽  
Growth Defects ◽  
Gram Positive Bacteria ◽  
Host Cell Death

ABSTRACTListeria monocytogenesis a Gram-positive intracellular pathogen that is naturally resistant to lysozyme. Recently, it was shown that peptidoglycan modification by N-deacetylation or O-acetylation confers resistance to lysozyme in various Gram-positive bacteria, includingL. monocytogenes.L. monocytogenespeptidoglycan is deacetylated by the action ofN-acetylglucosamine deacetylase (Pgd) and acetylated byO-acetylmuramic acid transferase (Oat). We characterized Pgd−, Oat−, and double mutants to determine the specific role ofL. monocytogenespeptidoglycan acetylation in conferring lysozyme sensitivity during infection of macrophages and mice. Pgd−and Pgd−Oat−double mutants were attenuated approximately 2 and 3.5 logs, respectively,in vivo. In bone-marrow derived macrophages, the mutants demonstrated intracellular growth defects and increased induction of cytokine transcriptional responses that emanated from a phagosome and the cytosol. Lysozyme-sensitive mutants underwent bacteriolysis in the macrophage cytosol, resulting in AIM2-dependent pyroptosis. Each of thein vitrophenotypes was rescued upon infection of LysM−macrophages. The addition of extracellular lysozyme to LysM−macrophages restored cytokine induction, host cell death, andL. monocytogenesgrowth inhibition. This surprising observation suggests that extracellular lysozyme can access the macrophage cytosol and act on intracellular lysozyme-sensitive bacteria.

Sign in / Sign up

Export Citation Format

Share Document