Disease relevance of hydrogen cyanide

• Early after contracture development, the resupply of extracellular Na+, in the continued presence of CN + 2-DG, resulted in a rapid partial relaxation (t1/2 = 1.9 +/- 0.3 seconds), associated with an increase in 45Ca efflux, presumably due to transsarcolemmal Ca2+ extrusion due to Na+-Ca2+ exchange [1].
• Oxygen, Cyanide and Energy Generation in the Cystic Fibrosis Pathogen Pseudomonas aeruginosa [2].
• The nonenzymatic release of free CN- from SNP was not inhibited by hypothermia, while the enzymatic detoxification of CN- to SCN- may have been delayed [3].
• 2. NADH autofluorescence measured at both 400 and 500 nm increased rapidly and reversibly in response to anoxia or to cyanide (CN-), reflecting a change in mitochondrial metabolism [4].
• 4. Removing the intracellular acidosis (by reducing the CO2 level of the gas with which the perfusate was equilibrated) during exposure to CN- and CHC caused an increase in developed pressure, consistent with the fall in pHi being responsible for a substantial fraction of the fall in developed pressure [5].

High impact information on hydrogen cyanide

• The discovery of hydrogen isocyanide (HNC) in comet Hyakutake with an abundance (relative to hydrogen cyanide, HCN) similar to that seen in dense interstellar clouds raised the possibility that these molecules might be surviving interstellar material [6].
• In contrast, paced ventricular myocytes superfused with 1 mM cyanide (CN) exhibited a similar increase in end-diastolic [Ca2+]i but a decrease in end-diastolic cell position and amplitude of motion [7].
• Hydrogen cyanide is linear triatomic molecule able to serve as a surrogate for carbon dioxide at the enzyme active site [8].
• Studies using the fluorescent Ca2+ probe indo 1 demonstrated that in zero-Na+-zero-Ca2+ solutions, contracture due to CN + 2-DG was associated with an initial rise in [Ca2+]i but that this did not account for all of contracture force development [1].
• Resupply of glucose and removal of CN + 2-DG, in the continued absence of Na+, resulted in an initially slower (t1/2 = 11.6 +/- 2.5 seconds), but more complete relaxation of contracture, which was not associated with increased Ca2+ efflux [1].

Chemical compound and disease context of hydrogen cyanide

• Hypoxia, however, failed to have any additional effect upon membrane currents in the presence of CN(-) or rotenone or the mitochondrial uncoupler p-trifluoromethoxyphenyl hydrazone (FCCP) [9].
• The time periods required for [Ca++]i to reach 50% of [Ca++]i transient ([Ca++]i-50) and contracture were determined after exposure to 1) CN + 2-DG alone, 2) CN + 2-DG simultaneous with 1 microM verapamil (V-sim) and 3) verapamil followed by CN + 2-DG (V-pre) [10].
• In contrast, only fructose treatment provided excellent cytoprotection against AA- and CN-induced toxicity [11].
• A few Pseudomonas species are able to form hydrocyanic acid (HCN), particularly when grown under glycine-rich conditions [12].
• Toxicity series based on 24-h LC50 may be established as follows: CN > SeO3 > Cr2O7 > NO2 > S2O3 >WO4 > BO3 [13].

Biological context of hydrogen cyanide

• Moreover, comets may have supplied a substantial fraction of the volatiles on the terrestrial planets, perhaps including organic compounds that played a role in the origin of life on Earth. Here we report the detection of hydrogen isocyanide (HNC) in comet Hyakutake [14].
• The endogenous detoxification of prussic acid exhibits zero-order kinetics [15].
• To elucidate underlying events, we used sodium cyanide (CN) as a pharmacological inhibitor of complex IV of the mitochondrial respiratory chain ('chemical hypoxia') and investigated the cellular response in vulnerable and resistant neurone types [16].
• PP2 prevented the CN-induced phosphorylation of these catenins [17].
• In the presence of CN the negativity of the resting membrane potential was slightly reduced [18].

Anatomical context of hydrogen cyanide

• We have shown that CN- increases a calcium-dependent potassium conductance (gK(Ca)) in single type I cells dissociated from the carotid body of the rabbit [19].
• A lack of thiosulphate can be detected early by a rise of the prussic acid concentration in the erythrocytes [15].
• Cyanides in the body form prussic acid, which can rapidly penetrate mucous and cell membranes [15].
• 3. Cyanide reversibly increased 86Rb efflux (30-35%) in both pregnant and nonpregnant uteri and contraction was reduced [20].
• 5. In the presence of either CN or IAA, spontaneous mechanical and electrical activities were reduced or eliminated, although amounts of high-energy phosphates sufficient to contract smooth muscle remained [18].

Associations of hydrogen cyanide with other chemical compounds

• We have therefore investigated the effects of rotenone, myxothiazol, antimycin A, cyanide (CN(-)) and oligomycin on isolated carotid body type I cells [9].
• In response to blockade of mitochondrial respiration and glycolysis with cyanide (CN-) and 2-deoxyglucose (DOG), [Mg2+]i rose more slowly but again KATP channel opening increased only when [Mg2+]i reached a plateau and the cells shortened [21].
• Verapamil (10(-5) mol l(-1)) and cyanide (CN, 10(-3) mol l(-1)) did not modify the accumulation of Ca2+ within the endolymph in the presence of a favourable calcium chemical gradient [22].
• 5) Cyanide-sensitive NADPH oxidation was inhibited by catalase and increased upon addition of H2O2 [23].
• A method to simulate gastrointestinal cyanide-release was applied to four different Prussian blue salts: K3Fe[Fe(CN)6], Fe4[Fe(CN)6]3, NH4Fe[Fe(CN)6] (pur. and unpur.). Cyanide-release was higher in artificial gastric juice than in water and artificial intestinal juice [24].
• Ruthenium dihydride phosphine was therefore used as a homogeneous catalyst, which significantly increases the nitrile hydrolysis rate [25].

Gene context of hydrogen cyanide

• In summary, we show that CN-induced chemical anoxia activates c-Src and induces its translocation to cell-cell junctions where it binds to and phosphorylates beta-catenin and p120 [17].
• During CN treatment, the proteins of the zonula adherens (ZA; E-cadherin and the catenins) disappeared from their normal location at cell-cell borders and appeared within the cytosol [17].
• This study identified four new roles for AlgR: (i) AlgR can repress gene transcription, (ii) AlgR activates the fimTU-pilVWXY1Y2E operon, (iii) AlgR regulates HCN production, and (iv) AlgR controls transcription of the putative cbb3-type cytochrome PA1557 [26].
• Additionally, direct measurement of hydrogen cyanide (HCN) production showed that P. aeruginosa PAO1 produced threefold-less HCN than did its algR deletion strain [26].
• The gacA gene of the biocontrol strain Pseudomonas fluorescens CHA0 codes for a response regulator which, together with the sensor kinase GacS (=LemA), is required for the production of exoenzymes and secondary metabolites involved in biocontrol, including hydrogen cyanide (HCN) [27].

Analytical, diagnostic and therapeutic context of hydrogen cyanide

• CN also elevated cytosolic [Ca2+] levels through (i) Ca2+ release from mitochondria-controlled stores, (ii) significant retardation of cytosolic Ca2+ clearance rates, even when cytosolic ATP levels were held constant during whole-cell recording, and (iii) secondary Ca2+ influx during elevated firing rates [16].
• 3. Cyanide perfusion during 10 min increased the threshold for excitation by 73 +/- 79 pA (p = 0.001), which differed from the effect in control cells (11 +/- 41 pA, ns) [28].
• beta-Cyanoalanine synthase (beta-cyano-l-alanine synthase; l-cysteine: hydrogen sulphide lyase (adding hydrogen cyanide (HCN)); EC 4. 4.1.9) was purified from the cytosolic fraction of the gut of grasshopper Zonocerus variegatus (L.) by ion-exchange chromatography on DEAE-Cellulose and gel filtration on Sephadex G-100 columns [29].
• Partial reduction of mitochondrial respiration, achieved by titration with cyanide (CN), strongly stimulated glycolytic flux but did not affect ATP contents of hepatocytes from both species [30].
• The hydrocyanic acid content of wild cherry (Prunus spp) decreased after treatment with 2,4-D and 2,4,5-T, but increased in Sudangrass (Sorghum halapense) after treatment with 2,4-D [31].

References