title: Multi-effective properties of homogentisic acid revealed in reactions with human hemoglobin and human erythrocytic hemoglobin.
abstract: Homogentisic acid (HGA) causes oxidation of human oxyhemoglobin and reduction of methemoglobin. The rate of oxidation of oxyhemoglobin by HGA is greatly accelerated in the presence of myo-inositol hexakis-phosphate (P6-inositol) or superoxide dismutase (SOD), but is inhibited in the presence of catalase. The reduction rate of methemoglobin by HGA is accelerated in the presence of P6-inositol but is greatly inhibited in the presence of SOD. It is suggested that the semiquinone and quinone form of HGA and oxygen radicals may be involved in the mechanism of oxido-reductive reactions of human hemoglobin with HGA. In addition, a new anodic hemoglobin found by isoelectric focusing electrophoresis was produced during the reaction of oxyhemoglobin with HGA. When human erythrocytes were exposed to HGA for several hours at 37 degrees C (pH 7.4), the anodic oxyhemoglobin (HGA-modified hemoglobin) and its half met-form hemoglobin [(alpha3+beta2+)2 of HGA-modified hemoglobin] were produced in significant amounts. HGA-modified hemoglobin was stably purified and showed increased oxygen affinity, absence of titratable sulfhydryl groups, and the absorption spectrum of normal oxyhemoglobin. Our results demonstrate that HGA shows multiple effects on human hemoglobin and erythrocytic hemoglobin, which is consistent with the evidence that HGA is involved in various pathological conditions such as arthritis and carcinogenesis in humans.
authors.affiliation: Department of Geriatric Medicine, Tokyo Medical University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yoneda
authors.forename: M
authors.initials: M
authors.lastname: Akazawa
authors.forename: J
authors.initials: J
authors.lastname: Koizumi
authors.forename: M
authors.initials: M
authors.lastname: Takasaki
authors.forename: J
authors.initials: J
authors.lastname: Yamaguchi
authors.forename: A
authors.initials: A
authors.lastname: Tomoda
mesh_terms: D004912:Erythrocytes / Q000378:metabolism*; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D006713:Homogentisic Acid / Q000737:chemistry / Q000378:metabolism*; D006801:Humans
chemical_list: D006454:Hemoglobins; D006713:Homogentisic Acid