Aminoacetone Research Articles

Complex Organic Molecules Formation in Space Through Gas Phase Reactions: A Theoretical Approach

Abstract Chemistry in the interstellar medium (ISM) is capable of producing complex organic molecules (COMs) of great importance to astrobiology. Gas phase and grain surface chemistry almost certainly both contribute to COM formation. Amino acids as building blocks of proteins are some of the most interesting COMs. The simplest one, glycine, has been characterized in meteorites and comets and, its conclusive detection in the ISM seems to be highly plausible. In this work, we analyze the gas phase reaction of glycine and to establish the role of this process in the formation of alanine or other COMs in the ISM. Formation of protonated α- and β-alanine in spite of being exothermic processes is not viable under interstellar conditions because the different paths leading to these isomers present net activation energies. Nevertheless, glycine can evolve to protonated 1-imide-2, 2-propanediol, protonated amino acetone, protonated hydroxyacetone, and protonated propionic acid. However, formation of acetic acid and protonated methylamine is also a favorable process and therefore will be a competitive channel with the evolution of glycine to COMs.

Amino–Acetone‐Bridged Cyclodextrins ― Artificial Alcohol Oxidases

AbstractA new series of α‐ and β‐cyclodextrin derivatives containing a substituted amino–acetone bridge attached to the 6A and 6D positions of the cyclodextrin are reported. The synthesis starts from the known α‐ or β‐cyclodextrin A,D‐diols, which were either oxidized to α‐ or β‐cyclodextrin A,D‐dicarbaldehydes and then coupled with 1,3‐diamino‐2‐propanol by a reductive amination reaction and further modified to give the final 6A,6D‐diamino‐6A,6D‐dideoxy‐N,N′‐(2‐oxopropa‐1,3‐dienyl)‐N,N′‐acetyl‐α‐ or ‐β‐cyclodextrin or the cyclodextrin‐diol was substituted with azide then reduced and after a few alkylation steps the final 6A,6D‐dideoxy‐N,N′‐(2‐oxopropa‐1,3‐dienyl)‐6A,6D‐(N,N,N′N′‐tetramethyldiammonio)‐α‐cyclodextrin dibromide was obtained. The new compounds display very good enzymatic catalytic properties in the oxidation of benzyl alcohols with a rate increase of up to 18500 but only appreciable catalysis for aniline oxidations. Thus, unlike previously studied cyclodextrin ketones, these new amino–acetone‐bridged cyclodextrins have high substrate selectivity and also exhibit stereoselectivity in the oxidation of different enantiomers.

Aminoacetone, a Putative Endogenous Source of Methylglyoxal, Causes Oxidative Stress and Death to Insulin-Producing RINm5f Cells

Aminoacetone (AA), triose phosphates, and acetone are putative endogenous sources of potentially cytotoxic and genotoxic methylglyoxal (MG), which has been reported to be augmented in the plasma of diabetic patients. In these patients, accumulation of MG derived from aminoacetone, a threonine and glycine catabolite, is inferred from the observed concomitant endothelial overexpression of circulating semicarbazide-sensitive amine oxidases. These copper-dependent enzymes catalyze the oxidation of primary amines, such as AA and methylamine, by molecular oxygen, to the corresponding aldehydes, NH4(+) ion and H2O2. We recently reported that AA aerobic oxidation to MG also takes place immediately upon addition of catalytic amounts of copper and iron ions. Taking into account that (i) MG and H2O2 are reportedly cytotoxic to insulin-producing cell lineages such as RINm5f and that (ii) the metal-catalyzed oxidation of AA is propagated by O2(*-) radical anion, we decided to investigate the possible pro-oxidant action of AA on these cells taken here as a reliable model system for pancreatic beta-cells. Indeed, we show that AA (0.10-5.0 mM) administration to RINm5f cultures induces cell death. Ferrous (50-300 microM) and Fe(3+) ion (100 microM) addition to the cell cultures had no effect, whereas Cu(2+) (5.0-100 microM) significantly increased cell death. Supplementation of the AA- and Cu(2+)-containing culture medium with antioxidants, such as catalase (5.0 microM), superoxide dismutase (SOD, 50 U/mL), and N-acetylcysteine (NAC, 5.0 mM) led to partial protection. mRNA expression of MnSOD, CuZnSOD, glutathione peroxidase, and glutathione reductase, but not of catalase, is higher in cells treated with AA (0.50-1.0 mM) plus Cu(2+) ions (10-50 microM) relative to control cultures. This may imply higher activity of antioxidant enzymes in RINm5f AA-treated cells. In addition, we have found that AA (0.50-1.0 mM) plus Cu(2+) (100 microM) (i) increase RINm5f cytosolic calcium; (ii) promote DNA fragmentation; and (iii) increase the pro-apoptotic (Bax)/antiapoptotic (Bcl-2) ratio at the level of mRNA expression. In conclusion, although both normal and pathological concentrations of AA are probably much lower than those used here, it is tempting to propose that excess AA in diabetic patients may drive oxidative damage and eventually the death of pancreatic beta-cells.

Signal Peptide Peptidase and γ-Secretase Share Equivalent Inhibitor Binding Pharmacology

The enzyme gamma-secretase has long been considered a potential pharmaceutical target for Alzheimer disease. Presenilin (the catalytic subunit of gamma-secretase) and signal peptide peptidase (SPP) are related transmembrane aspartyl proteases that cleave transmembrane substrates. SPP and gamma-secretase are pharmacologically similar in that they are targeted by many of the same small molecules, including transition state analogs, non-transition state inhibitors, and amyloid beta-peptide modulators. One difference between presenilin and SPP is that the proteolytic activity of presenilin functions only within a multisubunit complex, whereas SPP requires no additional protein cofactors for activity. In this study, gamma-secretase inhibitor radioligands were used to evaluate SPP and gamma-secretase inhibitor binding pharmacology. We found that the SPP enzyme exhibited distinct binding sites for transition state analogs, non-transition state inhibitors, and the nonsteroidal anti-inflammatory drug sulindac sulfide, analogous to those reported previously for gamma-secretase. In the course of this study, cultured cells were found to contain an abundance of SPP binding activity, most likely contributed by several of the SPP family proteins. The number of SPP binding sites was in excess of gamma-secretase binding sites, making it essential to use selective radioligands for evaluation of gamma-secretase binding under these conditions. This study provides further support for the idea that SPP is a useful model of inhibitory mechanisms and structure in the SPP/presenilin protein family.

Aminoacetone Induces Oxidative Modification to Human Plasma Ceruloplasmin

Aminoacetone (AA), a putative endogenous source of cytotoxic methylglyoxal, and ceruloplasmin (CP), the antioxidant plasma copper transporter, are known to increase in diabetes. AA was recently shown in vitro to act as a pro-oxidant toward ferritin and isolated mitochondria. We now report AA oxidative effects on CP mediated by AA-generated reactive oxygen species (ROS). Incubation of 1.5 microM human CP with 0.05-1 mM AA resulted in extensive protein aggregation. That ROS-driven thiol cross-linking underlies the CP aggregation was evidenced by the inhibitory effects of added superoxide dismutase, catalase, mannitol, and dithiothreitol. The addition of CP to AA (mM) solutions accelerated oxygen consumption by AA and caused CP copper ion release and loss of ferroxidase and aminoxidase activities. If operative in vivo, this reaction would impair the antioxidant role of CP and iron uptake by ferritin and hence contribute to intracellular iron-induced oxidative stress during AA accumulation in diabetes mellitus.

Aminoacetone induces iron-mediated oxidative damage to isolated rat liver mitochondria

Aminoacetone (AA) is a threonine metabolite accumulated in threoninemia, cri-du-chat, and diabetes, where it contributes toward the formation of cytotoxic and genotoxic methylglyoxal (MG). Oxyradicals yielded from iron-catalyzed AA aerobic oxidation to MG are shown here to promote Ca 2+-mediated mitochondrial membrane permeabilization in an AA dose-dependent way. The inhibitory effect of added EGTA, cyclosporin A, Mg 2+, and DTT observed in this study suggests the formation of transition pores in the inner mitochondrial membrane by AA, associated with thiol protein aggregation. That the mitochondrial iron pool plays a coadjutant role in the transition of mitochondrial permeability is indicated by the dramatic inhibitory effect of added o-phenanthroline. Iron released from ferritin by AA oxidation products—superoxide anion and AA enolyl radicals—is shown to act as an alternative source of ferrous iron, intensifying the mitochondrial damage. These findings may contribute to clarify the role of accumulated AA and iron overload in the mitochondrial oxidative damage reportedly occurring in diabetes mellitus.

Aerobic oxidation of aminoacetone, a threonine catabolite: iron catalysis and coupled iron release from ferritin.

Aminoacetone (AA) is a threonine and glycine catabolite long known to accumulate in cri-du-chat and threoninemia syndromes and, more recently, implicated as a contributing source of methylglyoxal (MG) in diabetes mellitus. Oxidation of AA to MG, NH(4)(+), and H(2)O(2) has been reported to be catalyzed by a copper-dependent semicarbazide sensitive amine oxidase (SSAO) as well as by Cu(II) ions. We here study the mechanism of AA aerobic oxidation, in the presence and absence of iron ions, and coupled to iron release from ferritin. Aminoacetone (1-7 mM) autoxidizes in Chelex-treated phosphate buffer (pH 7.4) to yield stoichiometric amounts of MG and NH(4)(+). Superoxide radical was shown to propagate this reaction as indicated by strong inhibition of oxygen uptake by superoxide dismutase (SOD) (1-50 units/mL; up to 90%) or semicarbazide (0.5-5 mM; up to 80%) and by EPR spin trapping studies with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which detected the formation of the DMPO-(*)OH adduct as a decomposition product from the DMPO-O(2)(*)(-) adduct. Accordingly, oxygen uptake by AA is accelerated upon addition of xanthine/xanthine oxidase, a well-known enzymatic source of O(2)(*)(-) radicals. Under Fe(II)EDTA catalysis, SOD (<50 units/mL) had little effect on the oxygen uptake curve or on the EPR spectrum of AA/DMPO, which shows intense signals of the DMPO-(*)OH adduct and of a secondary carbon-centered DMPO adduct, attributable to the AA(*) enoyl radical. In the presence of iron, simultaneous (two) electron transfer from both Fe(II) and AA to O(2), leading directly to H(2)O(2) generation followed by the Fenton reaction is thought to take place. Aminoacetone was also found to induce dose-dependent Fe(II) release from horse spleen ferritin, putatively mediated by both O(2)(*)(-) and AA(*) enoyl radicals, and the co-oxidation of added hemoglobin and myoglobin, which may be viewed as the initial step for potential further iron release. It is thus tempting to propose that AA, accumulated in the blood and other tissues of diabetics, besides being metabolized by SSAO, may release iron and undergo spontaneous and iron-catalyzed oxidation with production of reactive H(2)O(2) and O(2)(*)(-), triggering pathological responses. It is noteworthy that noninsulin-dependent diabetes has been frequently associated with iron overload and oxidative stress.

Release of Signal Peptide Fragments into the Cytosol Requires Cleavage in the Transmembrane Region by a Protease Activity That Is Specifically Blocked by a Novel Cysteine Protease Inhibitor

Signal peptides of secretory and membrane proteins are generated by proteolytic processing of precursor proteins after insertion into the endoplasmic reticulum membrane. Liberated signal peptides can be further processed, and the resulting N-terminal fragments are released toward the cytosol, where they may interact with target proteins like calmodulin. We show here that the processing of signal peptides requires a protease activity distinct from signal peptidase. This activity is inhibited specifically with a newly developed cysteine protease inhibitor, 1, 3-di-(N-carboxybenzoyl-l-leucyl-l-leucyl)amino acetone ((Z-LL)(2) ketone). Inhibitor studies revealed that the final, (Z-LL)(2) ketone-sensitive cleavage event occurs within the hydrophobic transmembrane region of the signal peptide, thus promoting the release of an N-terminal fragment into the cytosol.

Study on the Oscillating Belousov-Zhabotinskii Type Reaction of Seven Amino Acids

Using potentiometric method, we first report the behavior of the oscillating reaction of seven amino acids (L-threonine, L-arginine, L-leucine, L-histidine, L-glutamic acid, L-glycine and DL-alanine) in amino acid-BrO_3~--H~+-M_n~(2+)-acetone system. The oscillating B-Z type reaction using amino acid and acetone as mixed organic substrates has not yet been investigated.

Excretion of delta-aminolevulinic acid in the absence of demonstrable erythropoiesis.

Delta-aminolevulinic acid (ALA), a precursor of heme synthesis, was found to be present in normal amounts in the urine of patients without demonstrable erythropoiesis. The presence of true ALA in the urine of these patients was confirmed by a new method using an automatic amino-acid analyzer. By this method, the interfering substances such as glucosamine and amino acetone were eliminated.

THE CHROMATOGRAPHIC SEPARATION, DETERMINATION, AND DAILY EXCRETION OF URINARY PORPHOBILINOGEN, AMINO ACETONE, AND DELTA-AMINOLEVULINIC ACID.

Journal Article The Chromatographic Separation, Determination, and Daily Excretion of Urinary Porphobilinogen, Amino Acetone, and δAminolevulinic Acid. Get access Frank S. Schlenker, PH.D., Frank S. Schlenker, PH.D. Biochemical Research Section, Medical Research Laboratory, Veterans Administration Medical Teaching Group Hospital, Memphis, Tennessee Search for other works by this author on: Oxford Academic Google Scholar N. Ann Taylor, B.S., N. Ann Taylor, B.S. Biochemical Research Section, Medical Research Laboratory, Veterans Administration Medical Teaching Group Hospital, Memphis, Tennessee Search for other works by this author on: Oxford Academic Google Scholar Bettie P. Kiehn, M.T. (ASCP) Bettie P. Kiehn, M.T. (ASCP) Biochemical Research Section, Medical Research Laboratory, Veterans Administration Medical Teaching Group Hospital, Memphis, Tennessee Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 42, Issue 4, 1 October 1964, Pages 349–354, https://doi.org/10.1093/ajcp/42.4.349 Published: 01 October 1964 Article history Received: 06 April 1964 Accepted: 28 May 1964 Published: 01 October 1964

Aminoacetone formation by Staphylococcus aureus.

Aminoacetone formation by Staphylococcus aureus.

231. Self-condensation of acetamidoacetaldehyde and of aminoacetone

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