Coupled oxidation of ascorbic acid and haemoglobin

Lemberg, R.; Lockwood, W. H.; Legge, J. W.

doi:10.1042/bj0350363

Cited by 41 publications

(30 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Coupled Oxidation of meso-Methylmesoheme⅐hHO-1 Complexes-Coupled oxidation is the oxidation of heme to biliverdin promoted by ascorbate or other reducing agents (28,29). Ascorbate specifically supports the conversion of the heme⅐hHO-1 complex to biliverdin IX␣ (30).…”

Section: Formation Of Fe(iii)mesoverdoheme With H 2 O 2 -Previousmentioning

confidence: 99%

Oxidation of the meso-Methylmesoheme Regioisomers by Heme Oxygenase

Torpey

Montellano

1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

The oxidation of heme by heme oxygenase (HO-1) results in highly regiospecific extrusion of the ␣-mesocarbon as CO and the formation of biliverdin IX␣. The first step in the accepted mechanism for this process is ␣-meso-hydroxylation of the heme. To define further the reaction mechanism, the oxidations of the four isomers of meso-methylmesoheme by human truncated HO-1 supported by NADPH-cytochrome P450 reductase, H 2 O 2 , or ascorbate have been examined. Surprisingly, the results establish that (a) HO-1 can oxidize an ␣-meso-methyl-substituted heme to biliverdin IX␣ without proceeding via the ␣-meso-hydroxy intermediate; (b) the normal HO-1 ␣-regiospecificity is inverted in favor of the substituted ␥-position by introduction of a ␥-meso methyl group; and (c) the ␤-and ␦-meso-methylmesohemes are oxidized less regiospecifically to mixtures of methylsubstituted and -unsubstituted mesobiliverdins. The results indicate that electronic rather than steric effects primarily control the regiospecificity of heme cleavage by HO-1.Heme oxygenase, which oxidizes heme 1 to biliverdin IX␣ and CO ( Fig. 1), is of particular interest because of the physiological activities of its reaction products. Biliverdin, which functions as an endogenous antioxidant (1), is reduced to bilirubin and is excreted after conjugation with glucuronic acid (2). However, the excretion of bilirubin is often impaired in newborn children and in other individuals with a glucuronyltransferase deficiency (3). The neurotoxic properties of unconjugated bilirubin make its accumulation undesirable, and inhibition of heme oxygenase is one possible approach to the treatment of this problem. More recently, a potentially important but controversial role as a second messenger akin to nitric oxide has been proposed for the CO produced by heme oxygenase (4 -6).Two forms of heme oxygenase are known: HO-1, which is induced by a variety of agents and stress conditions and is found in highest concentration in the spleen and liver, and HO-2, which is not induced by xenobiotics and is found in highest concentration in the brain and testes (7,8). Human HO-1 is a 32-kDa protein with a C-terminal lipophilic domain that anchors it to the endoplastic reticulum (9). We have demonstrated that a fully active truncated version of human HO-1 (hHO-1) lacking the 23 C-terminal amino acids that constitute the membrane anchor can be expressed in Escherichia coli in high yields (10). A protein lacking the 26 N-terminal amino acids in which the last two amino acids have been mutated (S262R, S263L) has been independently expressed and shown to retain partial activity (11).The heme oxygenase reaction proceeds via a multistep mechanism that depends on reduction equivalents provided by NADPH and P450 reductase. The first step of the reaction is thought to be the O 2 -dependent oxidation of heme to ␣-mesohydroxyheme (Fig. 1). The principal experimental evidence for this intermediate is the finding that synthetic ␣-meso-hydroxyheme is converted to biliverdin IX␣ both by HO-1 (12, 13) and by a...

show abstract

Section: Formation Of Fe(iii)mesoverdoheme With H 2 O 2 -Previousmentioning

confidence: 99%

Oxidation of the meso-Methylmesoheme Regioisomers by Heme Oxygenase

Torpey

Montellano

1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Reviewing the course of the severest cases, it is apparent that transfusion was of no great benefit, 12 Two hundred cc. of pooled blood of dogs was laked with distilled water and centrifuged.…”

Section: Methodsmentioning

confidence: 99%

Acute Hemolytic Anemia From the Sulfonamides

Fox

Ottenberg²

1941

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Bile Pigment Precursors in Normal Human Erythrocytes BY C. GARDIKAS, J. E. KENCH AND J. F. WILKINSON Department of Haematology, Manchester Royal Infirnmary (Received 4 July 1949) In studies on the in vitro breakdown of haemoglobin Lemberg, Lockwood & Legge (1941) have obtained evidence of the occurrence of a chromoprotein intermediate, to which they have given the name choleglobin. The presence of this substance in the reaction mixture of ascorbic acid and oxyhaemoglobin is revealed by the appearance of a new absorption spectrum, and treatment with acetic acid will then liberate the bile pigments, biliverdin and bilipurpurin.…”

mentioning

confidence: 99%

Bile pigment precursors in normal human erythrocytes

Gardikas

Kench

Wilkinson

1950

Biochemical Journal

View full text Add to dashboard Cite

Vol. 46 COMPOSITION OF HORSE OIL 85 3. The virtual absence of linolenic acid in the ox and sheep, as compared with its presence in quantity in the horse, the rabbit, and the pasture on which these animals feed, would indicate a difference in the nature of fat metabolism of these animals.The authors desire to thank the manager, Mr N. A. Thomson, and staff of the Auckland Farmers' Freezing Company Ltd., for placing at their disposal information and assistance which greatly facilitated the carrying out of this investigation.

show abstract

Coupled oxidation of ascorbic acid and haemoglobin

Cited by 41 publications

References 2 publications

Oxidation of the meso-Methylmesoheme Regioisomers by Heme Oxygenase

Oxidation of the meso-Methylmesoheme Regioisomers by Heme Oxygenase

Acute Hemolytic Anemia From the Sulfonamides

Bile pigment precursors in normal human erythrocytes

Contact Info

Product

Resources

About