Hemoglobins cyanide

Figure 19. A density gradient electrofocusing experiment run in the apparatus depicted in Fig. 17 with the electric field on during elution according to Svendsen (128). The apparatus was fitted with a cold finger. The gradient had a height of 21 cm and a cross section of 7.2 cm. It was a run for 48 hours at 17°C. The protein load was 6.5 mg human hemoglobine cyanide. Elution was done with an input of 2.25 ml/h and an output of 13.7 ml/h. Fractions were taken so that one fraction corresponded to 0.1 cm column height. The fractions were read on a spectrophotometer. However, pH determination cannot be done since every sample is diluted with phosphoric acid during the elution. (Svendsen, 56).

The automated method differs from the ICSH method chiefly in that oxidation and ligation of heme iron occur after the hemes have been released from globin. Therefore, ferricyanide and cyanide need not diffuse into the hemoglobin and methemoglobin, respectively. Because diffusion is rate-limiting in this reaction sequence, the overall reaction time is reduced from approximately three minutes for the manual method to 3 —15 seconds for the automated method. Reaction sequences in the Coulter S + II and the Technicon H 1 and H 2 are similar. Moreover, similar reactions are used in the other Coulter systems and in the TOA and Unipath instmments. 

Mintorovitch, J., D.V. Pelt, and J.D. Satterlee. 1989. Kinetic study of the slow cyanide binding to Glycera dibranchiata monomer hemoglobin components HI and IV. Biochemistry 28 6099-6104. 

Hydroxyurea reacts with oxy, deoxy and metHb in vitro to form iron nitrosyl hemoglobin (HbNO) and transfers NO to 2-6% of the iron heme groups [115]. Trapping studies using cyanide and carbon monoxide indicate that hydroxyurea oxidizes both oxy and deoxyHb to metHb and reduces metHb to deoxyHb specifically identifying the reaction of hydroxyurea and metHb as the critical reaction in the formation of HbNO from hydroxyurea [115]. Scheme 7.16 depicts the proposed mechanisms of N O and HbNO formation during the reaction of deoxy and metHb with hydroxyurea. Oxidation of hydroxyurea by metHb produces deoxyHb and the nitroxide radical (25,... 

HCN in the blood is almost completely contained in the red blood cells where it is bound to methemoglobin. Immediately after infusion of sodium nitroprusside into patients, 98.4% of the blood cyanide was found in the red blood cells (Vesey et al. 1976). At normal physiological levels of body methemoglobin (0.25% to 1% of the hemoglobin), a human adult can bind about 10 mg of HCN (Schulz 1984). 

Nitrites may be used as an antidote for cyanide poisoning if given rapidly. They convert hemoglobin to methemoglobin, which binds cyanide in the blood before reaching the tissues. Oxygen is also given if possible. 

Carbon monoxide binds to cytochrome a/Oj but less tightly than cyanide. It also binds to hemoglobin, displacing oxygen. Symptoms include headache, nausea, tachycardia, and tachypnea. Lips and cheeks turn a cherry-red color. Respiratory depression and coma result in death if not treated by giving oxygen. Sources of carbon monoxide include ... 

Finally, it should be mentioned that HA is effective as an antidote against cyanide poisoning by virtue of converting ca 20% of the hemoglobin to methemoglobin. This will be discussed at length in Section ILF. 

The toxicity of CO (and, in a sense, of the isoelectronic cyanide ion, CN-) is a direct consequence of this, as CO will compete effectively with 02 for the iron centers of the hemoglobin (Hb) in blood ... 

The administration of sodium thiosulfate (12.5 grams a 25 percent solution administered intravenously at a flow rate of 2.5-5mL/min over a 10-minute period of time) will result in the conversion of the much more toxic cyanide to its less toxic thiocyanate form. This treatment of cyanide poisoning with sodium thiosulfate should follow the use of sodium nitrite. The administration of both the sodium nitrite and sodium thiosulfate is dependent upon the hemoglobin of the patient. The Fe2+ form of hemoglobin will also be oxidized by the sodium thiosulfate and sodium nitrite to the Fe3+ form (methemoglobin). This oxidized form binds cyanide readily to form a stable complex which can be metabolized. See ASIDEon CYANIDE. 

Two examples of toxicity, where the target is known, are carbon monoxide, which interacts specifically with hemoglobin, and cyanide, which interacts specifically with the enzyme cytochrome a3 of the electron transport chain (see chap. 7). The toxic effects of these two compounds are a direct result of these interactions and, it is assumed, depend on the number of molecules of the toxic compound bound to the receptors. However, the final toxic effects involve cellular damage and death and also depend on other factors. Other examples where specific receptors are known to be involved in the mediation of toxic effects are microsomal enzyme inducers, organophosphorus compounds, and peroxisomal proliferators (see chaps. 5-7). 

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