Search results for "Citric Acid Cycle"
showing 10 items of 39 documents
Polyamine Oxidase 5 loss-of-function mutations in Arabidopsis thaliana trigger metabolic and transcriptional reprogramming and promote salt stress to…
2017
The family of polyamine oxidases (PAO) in Arabidopsis (AtPAO1-5) mediates polyamine (PA) back-conversion, which reverses the PA biosynthetic pathway from spermine, and its structural isomer thermospermine (tSpm), into spermidine and then putrescine. Here, we have studied the involvement of PA back-conversion in Arabidopsis salinity tolerance. AtPAO5 is the Arabidopsis PAO gene member most transcriptionally induced by salt stress. Two independent loss-of-function mutants (atpao5-2 and atpao5-3) were found to exhibit constitutively higher tSpm levels, with associated increased salt tolerance. Using global transcriptional and metabolomic analyses, the underlying mechanisms were studied. Stimul…
Succinate receptor mediates intestinal inflammation and fibrosis.
2018
Succinate, an intermediate of the tricarboxylic acid cycle, is accumulated in inflamed areas and its signaling through succinate receptor (SUCNR1) regulates immune function. We analyze SUCNR1 expression in the intestine of Crohn's disease patients and its role in murine intestinal inflammation and fibrosis. We show that both serum and intestinal succinate levels and SUCNR1 expression in intestinal surgical resections were higher in CD patients than in controls. SUCNR1 co-localized with CD86, CD206, and alpha-SMA(+) cells in human intestine and we found a positive and significant correlation between SUCNR1 and alpha-SMA expression. In human isolated fibroblasts from CD patients SUCNR1 expres…
C 4 -Dicarboxylate Utilization in Aerobic and Anaerobic Growth
2016
C 4 -dicarboxylates and the C 4 -dicarboxylic amino acid l -aspartate support aerobic and anaerobic growth of Escherichia coli and related bacteria. In aerobic growth, succinate, fumarate, D - and L -malate, L -aspartate, and L -tartrate are metabolized by the citric acid cycle and associated reactions. Because of the interruption of the citric acid cycle under anaerobic conditions, anaerobic metabolism of C 4 -dicarboxylates depends on fumarate reduction to succinate (fumarate respiration). In some related bacteria (e.g., Klebsiella ), utilization of C 4 -dicarboxylates, such as tartrate, is independent of fumarate respiration and uses a Na + -dependent membrane-bound oxaloacetate decarbo…
CD4+ T-cell differentiation and function: Unifying glycolysis, fatty acid oxidation, polyamines NAD mitochondria
2021
The progression through different steps of T-cell development, activation, and effector function is tightly bound to specific cellular metabolic processes. Previous studies established that T-effector cells have a metabolic bias toward aerobic glycolysis, whereas naive and regulatory T cells mainly rely on oxidative phosphorylation. More recently, the field of immunometabolism has drifted away from the notion that mitochondrial metabolism holds little importance in T-cell activation and function. Of note, T cells possess metabolic promiscuity, which allows them to adapt their nutritional requirements according to the tissue environment. Altogether, the integration of these metabolic pathway…
Glycolysis/gluconeogenesis- and tricarboxylic acid cycle–related metabolites, Mediterranean diet, and type 2 diabetes
2020
Background: Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear. Objectives: We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions. Methods: We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were alloc…
Revisiting the Warburg effect: historical dogma versus current understanding
2020
Contrary to Warburg's original thesis, accelerated aerobic glycolysis is not a primary, permanent and universal consequence of dysfunctional or impaired mitochondria compensating for poor ATP yield per mole of glucose. Instead, in most tumours the Warburg effect is an essential part of a 'selfish' metabolic reprogramming, which results from the interplay between (normoxic/hypoxic) hypoxia-inducible factor-1 (HIF-1) overexpression, oncogene activation (cMyc, Ras), loss of function of tumour suppressors (mutant p53, mutant phosphatase and tensin homologue (PTEN), microRNAs and sirtuins with suppressor functions), activated (PI3K-Akt-mTORC1, Ras-Raf-MEK-ERK-cMyc, Jak-Stat3) or deactivated (LKB…
Lactate as a Metabolite and a Regulator in the Central Nervous System
2016
More than two hundred years after its discovery, lactate still remains an intriguing molecule. Considered for a long time as a waste product of metabolism and the culprit behind muscular fatigue, it was then recognized as an important fuel for many cells. In particular, in the nervous system, it has been proposed that lactate, released by astrocytes in response to neuronal activation, is taken up by neurons, oxidized to pyruvate and used for synthesizing acetyl-CoA to be used for the tricarboxylic acid cycle. More recently, in addition to this metabolic role, the discovery of a specific receptor prompted a reconsideration of its role, and lactate is now seen as a sort of hormone, even invol…
Arabidopsis Serine Decarboxylase 1 (SDC1) in Phospholipid and Amino Acid Metabolism
2018
Arabidopsis thaliana serine decarboxylase 1 (SDC1) catalyzes conversion of serine to ethanolamine, the first reaction step of phosphatidylcholine and phosphatidylethanolamine biosynthesis. However, an involvement of SDC1 in amino acid metabolism remains elusive despite that serine is the substrate of SDC1. Here, we showed that SDC1 localizes in mitochondria although phosphatidylcholine and phosphatidylethanolamine are known to be produced in the endoplasmic reticulum (ER). Moreover, we found that overexpression of SDC1 decreased levels of amino acid compounds derived from mitochondrial tricarboxylic acid cycle. These results suggest that mitochondria-localized SDC1 plays an important role i…
Functional differences between l- and d-carnitine in metabolic regulation evaluated using a low-carnitine Nile tilapia model.
2019
Abstractl-Carnitine is essential for mitochondrialβ-oxidation and has been used as a lipid-lowering feed additive in humans and farmed animals.d-Carnitine is an optical isomer ofl-carnitine anddl-carnitine has been widely used in animal feeds. However, the functional differences betweenl- andd-carnitine are difficult to study because of the endogenousl-carnitine background. In the present study, we developed a low-carnitine Nile tilapia model by treating fish with a carnitine synthesis inhibitor, and used this model to investigate the functional differences betweenl- andd-carnitine in nutrient metabolism in fish.l- ord-carnitine (0·4 g/kg diet) was fed to the low-carnitine tilapia for 6 wee…
Betaine and Choline Improve Lipid Homeostasis in Obesity by Participation in Mitochondrial Oxidative Demethylation
2018
We investigated the metabolic effects of betaine (Bet) supplementation on CTP:phosphoethanolamine cytidylyltransferase/Pcyt2 heterozygous mice (HET). HET received either no treatment or were allowed access to 1% Bet supplemented water for 8 weeks. As we previously showed with choline (Cho), Bet improved hypertriglyceridemia, and hepatic steatosis in HET. The protection from obesity associated with reduced hepatic steatosis and increased lipid breakdown in adipocytes was attributed to increased energy requirements for metabolism and elimination of supplemented Bet and Cho. 1H-NMR-based profiling revealed metabolic changes caused by Bet and Cho supplementation. Cho increased the citric acid c…