Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Archaea are the most extremophilic of the acidophilic microbes, combining, in many cases, acidophilicity with hyperthermophilicity. They form one of the three branches of the phylogenetic tree, and they are specifically found within the so-called crenarchaeota, typical members of which thrive at pH 1-3 and at temperatures of 75 degrees C to nearly 100 degrees C. Despite this, these cells can maintain a near neutral cytosol, and they use H+ for chemiosmotic coupling of ADP phosphorylation. These phenomena require efficient exclusion and disposal of protons. This is achieved by multiple synergistic mechanisms that act in parallel. One strategy is to use bipolar tetraether lipids as a matrix of their plasma membranes, providing low ion permeabilities, even at high temperatures. Additionally, an inverted membrane potential can help to balance a large pH gradient of up to 4 at a proton motive force of delta p = 140-180 mV. This is not a general rule, because in several species the membrane potential contributes only minimally. Also, local buffering capacity and charge profiles across the membrane may significantly influence adaptation to bulk phase acidity. Neither complex I nor complex III electron transport-coupled proton pump equivalents have been found in aerobic archaea. Only terminal oxidases seem to provide either H+ pumping or the generation of a proton gradient by chemical charge separation. Organization, redox centres and primary structures of some archaeal terminal quinol oxidase complexes are known and will be discussed. Much less is known about anaerobic sulfur reducers. For those a possible mechanism for proton exclusion is proposed.
 ...
PMID:How can archaea cope with extreme acidity? 1020 17

The title organo-molybdate derivatives are synthesized and their IR, 1H NMR spectra have been determined and the relations between the structures and the 1H NMR and IR parameters have been studied. The results indicate that the red shift of the IR frequency of Mo-O-Mo in [(n-Bu)4N]2[Mo2O5(OC10H6O)2] (complex I) takes place to compare with that in [(n-Bu)4N]2[Mo4O10 (OC10H6O)2(OCH3)2] (complex II) and lower filed shift of 1H NMR of the aromatic H atoms in complex II occurs as contrasted to that in the complex I. It is found also the organo-molybdate derivatives are very sensitive to the acidity of the chemical system.
 ...
PMID:[The synthesis, 1H NMR and IR study of [(n-Bu)4N]2[Mo2O5(OC10H6O)2] and [(n-Bu)4N]2[Mo4O10 (OC10H6O)2(OCH3)2]]. 1294 21

The -CH(2)- group of the 2-nitrobenzyl pendant arm of the scorpionate complex I deprotonates in basic aqueous solution (pK(a) = 10.6), due to the coordination of the nitronate group to the nickel(II) center. Metal coordination enhances 2-nitrobenzene acidity by 10 orders of magnitude. [reaction: see text]
 ...
PMID:Dramatically enhanced carbon acidity of the nitrobenzyl fragment in a nickel(II) scorpionate complex. 1604 6

The result of sensory evaluation of sake showed that acetic acid imparted desirable acidity when the proportion of acetic acid to lactic acid was about 1/3, even if the concentration of acetic acid was 0.75 g/l. Glycerol balanced the acidity and brought about a harmony between sweetness and acidity in sake. A high-acetate producing sake yeast (MHA-3) was isolated from mutants having low NADH dehydrogenase (NDE) activity. MHA-3 produced 15 times more acetate and 5 times more lactate than the parental strain Kyokai no. 901 (K-901) in a small-scale sake brewing test using 10 kg of rice. In addition, the concentrations of glycerol in sake brewed with MHA-3 were approximately 1.5-fold higher than in that brewed with K-901. The proportion of acetic acid to lactic acid was about 1/3 in sake fermented with MHA-3 and it exhibited a good balance between sweetness and acidity. The activities of glycerol-3-phosphate dehydrogenase (GPD) and aldehyde dehydrogenase (ALD) in MHA-3 were 1.4-fold and 3.1-fold, respectively, higher than those in K-901 while the activity of NDE was 40% that of K-901. MHA-3 accumulated higher amounts of acetate and glycerol than K-901 in static YNB10 medium. The concentrations of acetic acid produced, depending on the quantity of yeast cells added, increased in conjunction with increases in glycerol produced. We suggest that NDE might be linked with GPD and that the nde mutants, which can be used in sake brewing, produced higher amounts of acetate and glycerol.
 ...
PMID:Isolation and characterization of a high-acetate-producing sake yeast Saccharomyces cerevisiae. 1623 68

Arctigenin, a mitochondrial complex I inhibitor, has been identified as a potential anti-tumor agent, but the involved mechanism still remains elusive. Herein, we studied the underlying mechanism(s) of action of arctigenin on acidity-tolerant prostate cancer PC-3AcT cells in the lactic acid-containing medium. At concentration showing no toxicity on normal prostate epithelial RWPE-1 and HPrEC cells, arctigenin alone or in combination with docetaxel induced significant cytotoxicity in PC-3AcT cells compared to parental PC-3 cells. With arctigenin treatment, reactive oxygen species (ROS) levels, annexin V-PE positive fractions, sub-G0/G1 peak in cell cycle analysis, mitochondrial membrane depolarization, and cell communication network factor 1 (CCN1) levels were increased, while cellular ATP content and phospho (p)-Akt level were decreased. Pretreatment with ROS scavenger N-acetylcysteine effectively reversed the series of phenomena caused by arctigenin, suggesting that ROS served as upstream molecules of arctigenin-driven cytotoxicity. Meanwhile, arctigenin increased the levels of p-receptor-interacting serine/threonine-protein kinase 3 (p-RIP3) and p-mixed lineage kinase domain-like pseudokinase (p-MLKL) as necroptosis mediators, and pretreatment with necroptosis inhibitor necrostatin-1 restored their levels and cell viability. Treatment of spheroids with arctigenin resulted in necroptotic cell death, which was prevented by N-acetylcysteine. The siRNA-based knockdown of CCN1 suppressed the levels of MLKL, B-cell lymphoma 2 (Bcl-2), and induced myeloid leukemia cell differentiation (Mcl-1) with increased cleavage of Bcl-2-associated X (Bax) and caspase-3. Collectively, these results provide new insights into the molecular mechanisms underlying arctigenin-induced cytotoxicity, and support arctigenin as a potential therapeutic agent for targeting non-Warburg phenotype through induction of necroptosis via ROS-mediated mitochondrial damage and CCN1 upregulation.
 ...
PMID:Arctigenin induces necroptosis through mitochondrial dysfunction with CCN1 upregulation in prostate cancer cells under lactic acidosis. 3206 51