Biomaterial Database

Excess release of ferriheme in G6PD-deficient erythrocytes: possible cause of hemolysis and resistance to malaria. 1986

S K Janney, and J J Joist, and C D Fitch

Hemoglobin in glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes is abnormally vulnerable to oxidative denaturation, which may release ferriheme, a known cytolytic agent. We found 13.3 nmol of ferriheme in G6PD-deficient erythrocyte membranes (per gram of total erythrocyte hemoglobin) using a spectrophotometric assay, as compared to 9.8 in normal membranes (P less than .05). After incubation of erythrocytes with 250 mumol/L menadione, an oxidant drug, the values increased by 37.4 nmol in G6PD-deficient membranes and by 26 in normal membranes (P less than .005), indicating increased hemoglobin denaturation. To verify that hemoglobin denaturation in G6PD-deficient erythrocytes releases ferriheme in a form available to interact with other ligands, [14C]-chloroquine binding to intact erythrocytes was measured. With an initial concentration of 5 mumol/L chloroquine in a medium containing no menadione, an excess of 14.8 nmol of chloroquine was bound in G6PD-deficient erythrocytes (per gram of hemoglobin) as compared to normal erythrocytes (P less than .005). In the presence of 250 mumol/L menadione, chloroquine binding increased by 17.9 nmol in G6PD-deficient and by 7.2 in normal erythrocytes (P less than .005). These results indicate that ferriheme becomes available to interact with endogenous ligands and, thus, to mediate menadione-induced hemolysis in patients with G6PD deficiency. Furthermore, the increase in ferriheme may mediate the selective toxicity of menadione for Plasmodium falciparum parasites growing in G6PD-deficient erythrocytes. Ferriheme release in response to the intraerythrocytic oxidant stress introduced by malaria parasites also may account for the resistance to malaria afforded by G6PD deficiency. This is a US government work. There are no restrictions on its use.

UI	MeSH Term	Description	Entries
D008288	Malaria	A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.	Marsh Fever,Plasmodium Infections,Remittent Fever,Infections, Plasmodium,Paludism,Fever, Marsh,Fever, Remittent,Infection, Plasmodium,Plasmodium Infection
D008297	Male		Males
D002738	Chloroquine	The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.	Aralen,Arechine,Arequin,Chingamin,Chlorochin,Chloroquine Sulfate,Chloroquine Sulphate,Khingamin,Nivaquine,Sulfate, Chloroquine,Sulphate, Chloroquine
D004910	Erythrocyte Membrane	The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.	Erythrocyte Ghost,Red Cell Cytoskeleton,Red Cell Ghost,Erythrocyte Cytoskeleton,Cytoskeleton, Erythrocyte,Cytoskeleton, Red Cell,Erythrocyte Cytoskeletons,Erythrocyte Ghosts,Erythrocyte Membranes,Ghost, Erythrocyte,Ghost, Red Cell,Membrane, Erythrocyte,Red Cell Cytoskeletons,Red Cell Ghosts
D005290	Ferric Compounds	Inorganic or organic compounds containing trivalent iron.	Compounds, Ferric
D005955	Glucosephosphate Dehydrogenase Deficiency	A disease-producing enzyme deficiency subject to many variants, some of which cause a deficiency of GLUCOSE-6-PHOSPHATE DEHYDROGENASE activity in erythrocytes, leading to hemolytic anemia.	Deficiency of Glucose-6-Phosphate Dehydrogenase,Deficiency, GPD,Deficiency, Glucosephosphate Dehydrogenase,G6PD Deficiency,GPD Deficiency,Glucose 6 Phosphate Dehydrogenase Deficiency,Glucose-6-Phosphate Dehydrogenase Deficiency,Glucosephosphate Dehydrogenase Deficiencies,Hemolytic Anemia Due to G6PD Deficiency,Deficiencies, G6PD,Deficiencies, GPD,Deficiencies, Glucose-6-Phosphate Dehydrogenase,Deficiencies, Glucosephosphate Dehydrogenase,Deficiency of Glucose 6 Phosphate Dehydrogenase,Deficiency, G6PD,Deficiency, Glucose-6-Phosphate Dehydrogenase,Dehydrogenase Deficiencies, Glucose-6-Phosphate,Dehydrogenase Deficiencies, Glucosephosphate,Dehydrogenase Deficiency, Glucose-6-Phosphate,Dehydrogenase Deficiency, Glucosephosphate,G6PD Deficiencies,GPD Deficiencies,Glucose-6-Phosphate Dehydrogenase Deficiencies
D006418	Heme	The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.	Ferroprotoporphyrin,Protoheme,Haem,Heme b,Protoheme IX
D006461	Hemolysis	The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.	Haemolysis,Extravascular Hemolysis,Intravascular Hemolysis,Extravascular Hemolyses,Haemolyses,Hemolyses, Extravascular,Hemolyses, Intravascular,Hemolysis, Extravascular,Hemolysis, Intravascular,Intravascular Hemolyses
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014812	Vitamin K	A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.