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Glutaric aciduria (type I)
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Considerable attention has been devoted to pathogenesis and the extraordinary vulnerability of the striatum, particularly the caudate and putamen. It has seemed likely that the accumulation of metabolites and something about the catabolic response to acute infection are relevant to neuronal damage. Glutaric acid and its metabolites are produced endogenously in the CNS and accumulate because of limiting transport mechanisms across the blood-brain barrier (trapping hypothesis) [60]. The similarity of structures of glutaric and glutamic acids, and the fact that glutaric and 3-hydroxyglutaric acids inhibit glutamate decarboxylase of brain [61] has led to an excitotoxic theory of neuronal damage in this disease. In striatal slice cultures, 3-hydroxyglutaric acid induced neuronal degeneration by activation of NMDA receptors [62]. Furthermore, glutaric and 3-hydroxyglutaric acids indirectly modulate glutamatergic and GABAergic neurotransmission, resulting in an imbalance of excitatory and inhibitory neurotransmission. Convulsions and striatal neuronal damage were caused in rats by direct striatal injection of 3-hydroxyglutaric acid [63]. Finally, glutaryl-CoA inhibits 2-oxoglutarate dehydrogenase complex in analogy to succinyl CoA [64] and by that the Krebs cycle.
Carbon Dioxide Sequestration by Microalgae
Published in Gokare A. Ravishankar, Ranga Rao Ambati, Handbook of Algal Technologies and Phytochemicals, 2019
G.V. Swarnalatha, Ajam Shekh, P.V. Sijil, C.K. Madhubalaji, Vikas Singh Chauhan, Ravi Sarada
The CO2 supplementation up-regulated the gene encoding the components of pyruvate dehydrogenase complex, which is a multienzyme complex catalyzing the conversion of pyruvate into acetyl Co-A for TCA cycle. Similarly, it has been observed that the genes encoding nearly all the enzymes of TCA cycle were up-regulated by the CO2 supplementation which includes citrate synthase, isocitrate dehydrogenase, aconitase, oxoglutarate, dehydrogenase, succinyl-CoA synthetase, and fumarase. This implies that the CO2 supplementation improves the TCA cycle providing more NADH, ATP, and GTP. In addition, the genes encoded for the enzymes for anapleurotic reactions including PEP carboxylase and pyruvate carboxylase (catalyzing the carboxylation of PEP and pyruvate, respectively) were up-regulated on CO2 supplementation providing more oxaloacetate to replenish the TCA cycle. Correspondingly, the genes involved in electron transport and oxidative phosphorylation were significantly up-regulated on CO2 supplementation. This includes several subunits of the Complex I (NADH dehydrogenase), III (cytochrome bc1 complex), IV (cytochrome c oxidase), and ATP synthase leading improved electron flow to the O2 and increased ATP production. This indicated that CO2 supplementation led to increased metabolic energy to sustain the increased growth of microalgae (Peng et al. 2016; Zhu et al. 2017).
Distribution and Biological Functions of Pyruvate Carboxylase in Nature
Published in D. B. Keech, J. C. Wallace, Pyruvate Carboxylase, 2018
Another interesting recent report on the Aspergillus nidulans pyruvate carboxylase has been the observation that 98% of its activity is found in the cytosol.618 Whereas pyruvate and 2-oxoglutarate dehydrogenases showed 99 to 100% latency, and citrate synthetase showed 15 to 20% latency when this parameter was assessed by assay in the presence or absence of 0.05% Non-Idet P40, pyruvate carboxylase and pyruvate kinase activities were fully expressed. Furthermore, while 95% of citrate synthetase and 100% of pyruvate, succinate, and 2-oxoglutarate dehydrogenase activities were sedimented by centrifuging at 12,000 g for 15 min, less than 1% of the pyruvate carboxylase and kinase activities were found in that pellet. These data demonstrate that pyruvate carboxylase is a cytosolic enzyme in Aspergillus nidulans, as is largely the case also in yeast.358 A cytosolic location for pyruvate carboxylase has important implications for the organization of lipid and amino acid biosynthesis in these lower eukaryotes.
Similar clinical outcome of AMA immunoblot-M2-negative compared to immunoblot-positive subjects over six years of follow-up
Published in Postgraduate Medicine, 2021
Stephan Zandanell, Michael Strasser, Alexandra Feldman, Georg Strebinger, Gerhild Aigner, David Niederseer, Martin Laimer, Birgit Mussnig, Bernhard Paulweber, Christian Datz, Elmar Aigner
The highly specific anti-mitochondrial antibodies (AMA) are the hallmark in the diagnosis of primary biliary cholangitis (PBC) [1]. Historically, nine subtypes of AMA have been postulated, of which four have been linked to PBC: AMA-M2, -M4, -M8, -M9 [2]. Only the M2 subtype, mainly directed against the E2 subunits of pyruvate dehydrogenase complex (PDC), branched-chain 2-oxoacid dehydrogenase complex (BCOADC) and 2-oxoglutarate dehydrogenase complex (OGDC) and to a lesser extent against the E1 and E3 domains of PDC, has proven to be of diagnostic value [3,4]. The other subtypes have been shown to be rather epiphenomena than real epitopes of PBC-specific autoantibodies [5]. M2 specificity can be confirmed in up to 90–95% of all AMA-positives [6,7].
Differences in the efficiency of 3-deazathiamine and oxythiamine pyrophosphates as inhibitors of pyruvate dehydrogenase complex and growth of HeLa cells in vitro
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Ewa Grabowska, Magdalena Czerniecka, Urszula Czyżewska, Aneta Zambrzycka, Zenon Łotowski, Adam Tylicki
Thiamine (Figure 1, No. 1) is one of the most important vitamins needed for proper cell metabolism. It performs several functions, of which the main is its role as a cofactor of important enzymes, such as pyruvate dehydrogenase complex (PDHC), transketolase, 2-oxoglutarate dehydrogenase complex and pyruvate decarboxylase1,2. For many years, several antimetabolites of thiamine [such as amprolium, metronidazole, pyrithiamine or oxythiamine (OT)] have been synthesised and tested as antibiotics or cytostatics3–6.
Proteomics and frailty: a clinical overview
Published in Expert Review of Proteomics, 2018
Elisa Danese, Martina Montagnana, Giuseppe Lippi
Thereon et al. carried out a similar study, comparing muscle protein profiles obtained from 10 mature and older women [35]. The authors identified three different clusters of proteins potentially associated with muscular aging. The first cluster encompassed mostly contractile proteins, thus including titin (TTN), ankyrin repeat domain-containing protein 2 (ANKRD2), myosin light chain 1/3 skeletal muscle isoform (MYL1), myosin-1 (MYH1), actin cytoplasmic 1 (ACTB), cofilin-1 (CFL1), and transgelin (TAGLN). The second and the third clusters predominantly included a set of proteins involved in energy metabolism, such as fatty acid-binding protein adipocyte (FABP4), aspartate aminotransferase mitochondrial (GOT2), fumarate hydratase mitochondrial (FH), and L-lactate dehydrogenase B chain (LDHB), ATP synthase subunit alpha mitochondrial (ATP5A1) and beta mitochondrial (ATP5B), carnitine O-acetyltransferase (CRAT), and ADP/ATP translocase 1 (SLC25A4). In a another study carried out by Gelfi et al., other enzymes involved in anaerobic metabolism, especially creatine kinase, were found to be less abundant in older subjects than in young adults [36]. Some enzymes involved in oxidative metabolism, such as ATP synthase β-chain, dihydrolipoamide dehydrogenase (DLD), Acyl-CoA dehydrogenase very long chain (VLCAD), three isoforms of aconitase, two isoforms of 2-oxoglutarate dehydrogenase (OGDH), malate dehydrogenase (MDH), and ubiquinol-cytochrome C reductase complex (cytochrome b-c1 complex), were also found to be more expressed in elderly than in young muscle [36]. Finally, Baraibar et al. reported that muscle aging may be mirrored by upregulation of molecular chaperones such as those belonging to the family of heat shock proteins, which are known to play an important role for preventing protein aggregation and maintaining cellular integrity during age-induced remodeling of muscle myofibers [37].