The synthesis of branched-chain fatty acids is limited by enzymatic decarboxylation of ethyl- and methylmalonyl-CoA
Most fatty acids (FAs) are straight chains and are synthesized by fatty acid synthase (FASN) using acetyl-CoA and malonyl-CoA units. Yet, FASN is known to be promiscuous as it may use methylmalonyl-CoA instead of malonyl-CoA and thereby introduce methyl-branches. We have recently found that the cytosolic enzyme ECHDC1 degrades ethylmalonyl-CoA and methylmalonyl-CoA, which presumably result from promiscuous reactions catalyzed by acetyl-CoA carboxylase on butyryl- and propionyl-CoA. Here, we tested the hypothesis that ECHDC1 is a metabolite repair enzyme that serves to prevent the formation of methyl- or ethyl-branched FAs ...
Source: Biochemical Journal - August 29, 2019 Category: Biochemistry Authors: Dewulf, J. P., Gerin, I., Rider, M. H., Veiga-da-Cunha, M., Van Schaftingen, E., Bommer, G. T. Tags: Research Articles Source Type: research
Broken force dispersal network in tip-links by the mutations at the Ca2+-binding residues induces hearing-loss
Tip-link as force-sensor in hearing conveys the mechanical force originating from sound to ion-channels while maintaining the integrity of the entire sensory assembly in the inner ear. This delicate balance between structure and function of tip-links is regulated by Ca2+-ions present in endolymph. Mutations at the Ca2+-binding sites of tip-links often lead to congenital deafness, sometimes syndromic defects impairing vision along with hearing. Although such mutations are already identified, it is still not clear how the mutants alter the structure-function properties of the force-sensors associated with diseases. With an a...
Source: Biochemical Journal - August 29, 2019 Category: Biochemistry Authors: Hazra, J. P., Sagar, A., Arora, N., Deb, D., Kaur, S., Rakshit, S. Tags: Research Articles Source Type: research
Rhizobacteria AK1 remediates the toxic effects of salinity stress via regulation of endogenous phytohormones and gene expression in soybean
In conclusion, AK1 can mitigate salinity stress, increase plant growth and could be utilized as an eco-friendly bio-fertilizer under salinity stress. (Source: Biochemical Journal)
Source: Biochemical Journal - August 29, 2019 Category: Biochemistry Authors: Khan, M. A., Asaf, S., Khan, A. L., Jan, R., Kang, S.-M., Kim, K.-M., Lee, I.-J. Tags: Research Articles Source Type: research
A novel small molecule A2A adenosine receptor agonist, indirubin-3'-monoxime, alleviates lipid-induced inflammation and insulin resistance in 3T3-L1 adipocytes
Saturated free fatty acid-induced adipocyte inflammation plays a pivotal role in implementing insulin resistance and type 2 diabetes. Recent reports suggest A2A adenosine receptor (A2AAR) could be an attractive choice to counteract adipocyte inflammation and insulin resistance. Thus, an effective A2AAR agonist devoid of any toxicity is highly appealing. Here, we report that indirubin-3'-monoxime (I3M), a derivative of the bisindole alkaloid indirubin, efficiently binds and activates A2AAR which leads to the attenuation of lipid-induced adipocyte inflammation and insulin resistance. Using a combination of in silico virtual ...
Source: Biochemical Journal - August 29, 2019 Category: Biochemistry Authors: Choudhary, S. A., Bora, N., Banerjee, D., Arora, L., Das, A. S., Yadav, R., Klotz, K.-N., Pal, D., Jha, A. N., Dasgupta, S. Tags: Research Articles Source Type: research
Autoactivation and calpain-1-mediated shedding of hepsin in human hepatoma cells
In this study, we conducted site-directed mutagenesis, cell expression, plasma membrane protein labeling, trypsin digestion, Western blotting, and flow cytometry experiments in human hepatoma HepG2 cells, where hepsin was originally discovered, and SMMC-7721 cells. Our results show that hepsin is activated by autocatalysis on the cell surface but not intracellularly. Moreover, we show that hepsin undergoes ectodomain shedding. In the conditioned medium from HepG2 and SMMC-7721 cells, we detected a soluble fragment comprising nearly the entire extracellular region of hepsin. By testing protease inhibitors, gene knockdown, a...
Source: Biochemical Journal - August 27, 2019 Category: Biochemistry Authors: Wang, L., Zhang, C., Sun, S., Chen, Y., Hu, Y., Wang, H., Liu, M., Dong, N., Wu, Q. Tags: Research Articles Source Type: research
The PHD finger of Spp1 mediates histone modification cross-talk
Binding of the Spp1 PHD finger to histone H3K4me3 is sensitive to adjacent post-translational modifications in the histone tail. This commentary discusses the findings of He and colleagues [Biochem. J. 476, 1957–1973] which show that the PHD finger binds to H3K4me3 in a selective manner which is conserved in the Saccharomyces pombe and mammalian orthologues of Spp1. (Source: Biochemical Journal)
Source: Biochemical Journal - August 27, 2019 Category: Biochemistry Authors: Musselman, C. A., Kutateladze, T. G. Tags: Commentaries Source Type: research
Pic1, counteracting plant immunity signalling
Plants are equipped with versatile pattern recognition receptors (PRRs), which monitor their external environment and elicit defensive measures upon detection of potential risk for disease. Inside the cell, receptor-like cytoplasmic kinases (RLCKs) are key components of PRR signalling, but their molecular functions and regulatory interactions are not yet fully understood. In tomato, two RLCKs, Pti1a and Pti1b, are important signalling components that relay early defence signals elicited by bacterial flagellin, a conserved pattern common to various pathogenic and non-pathogenic microbes. An important question to resolve is ...
Source: Biochemical Journal - August 27, 2019 Category: Biochemistry Authors: Kangasjärvi, S. Tags: Commentaries Source Type: research
The Great Escape: how phosphatidylinositol 4-kinases and PI4P promote vesicle exit from the Golgi (and drive cancer)
Phosphatidylinositol 4-phosphate (PI4P) is a membrane glycerophospholipid and a major regulator of the characteristic appearance of the Golgi complex as well as its vesicular trafficking, signalling and metabolic functions. Phosphatidylinositol 4-kinases, and in particular the PI4KIIIβ isoform, act in concert with PI4P to recruit macromolecular complexes to initiate the biogenesis of trafficking vesicles for several Golgi exit routes. Dysregulation of Golgi PI4P metabolism and the PI4P protein interactome features in many cancers and is often associated with tumour progression and a poor prognosis. Increased expressio...
Source: Biochemical Journal - August 27, 2019 Category: Biochemistry Authors: Waugh, M. G. Tags: Review Articles Source Type: research
Crystal structures of plant inorganic pyrophosphatase, an enzyme with a moonlighting autoproteolytic activity
Inorganic pyrophosphatases (PPases, EC 3.6.1.1), which hydrolyze inorganic pyrophosphate to phosphate in the presence of divalent metal cations, play a key role in maintaining phosphorus homeostasis in cells. DNA coding inorganic pyrophosphatases from Arabidopsis thaliana (AtPPA1) and Medicago truncatula (MtPPA1) were cloned into a bacterial expression vector and the proteins were produced in Escherichia coli cells and crystallized. In terms of their subunit fold, AtPPA1 and MtPPA1 are reminiscent of other members of Family I soluble pyrophosphatases from bacteria and yeast. Like their bacterial orthologs, both plant PPase...
Source: Biochemical Journal - August 21, 2019 Category: Biochemistry Authors: Grzechowiak, M., Ruszkowski, M., Sliwiak, J., Szpotkowski, K., Sikorski, M., Jaskolski, M. Tags: Research Articles Source Type: research
The human transmembrane mucin MUC17 responds to TNF{alpha} by increased presentation at the plasma membrane
Transmembrane mucin MUC17 is an integral part of the glycocalyx as it covers the brush border membrane of small intestinal enterocytes and presents an extended O-glycosylated mucin domain to the intestinal lumen. Here, we identified two unknown phosphorylated serine residues, S4428 and S4492, in the cytoplasmic tail of human MUC17. We have previously demonstrated that MUC17 is anchored to the apical membrane domain via an interaction with the scaffolding protein PDZK1. S4492, localized in the C-terminal PDZ binding motif of MUC17, was mutated to generate phosphomimetic and phosphodeficient variants of MUC17. Using Caco-2 c...
Source: Biochemical Journal - August 21, 2019 Category: Biochemistry Authors: Schneider, H., Berger, E., Dolan, B., Martinez-Abad, B., Arike, L., Pelaseyed, T., Hansson, G. C. Tags: Research Articles Source Type: research
A gene cluster for taurine sulfur assimilation in an anaerobic human gut bacterium
Aminoethylsulfonate (taurine) is widespread in the environment and highly abundant in the human body. Taurine and other aliphatic sulfonates serve as sulfur sources for diverse aerobic bacteria, which carry out cleavage of the inert sulfonate C–S bond through various O2-dependent mechanisms. Taurine also serves as a sulfur source for certain strict anaerobic fermenting bacteria. However, the mechanism of C–S cleavage by these bacteria has long been a mystery. Here we report the biochemical characterization of an anaerobic pathway for taurine sulfur assimilation in a strain of Clostridium butyricum from the huma...
Source: Biochemical Journal - August 14, 2019 Category: Biochemistry Authors: Xing, M., Wei, Y., Hua, G., Li, M., Nanjaraj Urs, A. N., Wang, F., Hu, Y., Zhai, W., Liu, Y., Ang, E. L., Zhao, H., Zhang, Y. Tags: Research Articles Source Type: research
Cancerous inhibitor of protein phosphatase 2A (CIP2A) modifies energy metabolism via 5' AMP-activated protein kinase signalling in malignant cells
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an adverse biomarker across many malignancies. Using K562 cells engineered to have high or low CIP2A expression, we show that high CIP2A levels significantly bias cellular energy production towards oxidative phosphorylation (OXPHOS) rather than glycolysis. Mass spectrometric analysis of CIP2A interactors and isobaric tagging for relative and absolute protein quantitation (ITRAQ) experiments identified many associated proteins, several of which co-vary with CIP2A level. Many of these CIP2A associating and co-varying proteins are involved in energy metabolism including...
Source: Biochemical Journal - August 14, 2019 Category: Biochemistry Authors: Austin, J. A., Jenkins, R. E., Austin, G. M., Glenn, M. A., Dunn, K., Scott, L., Lucas, C. M., Clark, R. E. Tags: Research Articles Source Type: research
ELP3 Acetyltransferase is phosphorylated and regulated by the oncogenic anaplastic lymphoma kinase (ALK)
Protein lysine acetylation is one of the major posttranslational modifications (PTMs) with several thousands of proteins identified to be acetylated in mammalian tissues. Mechanistic studies have revealed important functions of acetylation in the regulation of protein function. Much less is known on how the acetyltransferases themselves are regulated. In the current study, we discover that the Elongator protein 3 (ELP3) acetyltransferase is modified by tyrosine phosphorylation. We demonstrate that the anaplastic lymphoma kinase (ALK) is the major tyrosine kinase responsible for ELP3 tyrosine phosphorylation. ELP3 is phosph...
Source: Biochemical Journal - August 14, 2019 Category: Biochemistry Authors: Li, M.-T., Liang, J.-Y., Sun, Y.-P., Jin, J., Xiong, Y., Guan, K.-L., Yuan, H.-X. Tags: Research Articles Source Type: research
New tools for an old question: dependence of ATP and bicarbonate for branched-chain keto acids oxidation
Branched-chain keto acids (BCKA) metabolism involves several well-regulated steps within mitochondria, requires cofactors, and is modulated according to the metabolic status of the cells. This regulation has made it challenging to utilize in vitro approaches to determine the contribution of branched-chain amino acid oxidation to energy production. These methodological issues were elegantly addressed in a recent publication within the Biochemical Journal. In this issue, Goldberg et al. [Biochem. J. (2019) 476, 1521–1537] demonstrated in a well-designed system the dependence of ATP and bicarbonate for BCKA full oxidati...
Source: Biochemical Journal - August 14, 2019 Category: Biochemistry Authors: Brunetta, H. S., Holloway, G. P. Tags: Commentaries Source Type: research
Simple rules govern the diversity of bacterial nicotianamine-like metallophores
In metal-scarce environments, some pathogenic bacteria produce opine-type metallophores mainly to face the host's nutritional immunity. This is the case of staphylopine, pseudopaline and yersinopine, identified in Staphylococcus aureus, Pseudomonas aeruginosa and Yersinia pestis, respectively. Depending on the species, these metallophores are synthesized by two (CntLM) or three enzymes (CntKLM), CntM catalyzing the last step of biosynthesis using diverse substrates (pyruvate or α-ketoglutarate), pathway intermediates (xNA or yNA) and cofactors (NADH or NADPH). Here, we explored the substrate specificity of CntM by co...
Source: Biochemical Journal - August 8, 2019 Category: Biochemistry Authors: Laffont, C., Brutesco, C., Hajjar, C., Cullia, G., Fanelli, R., Ouerdane, L., Cavelier, F., Arnoux, P. Tags: Research Articles Source Type: research
