General toxicology
Timbrell John in Study Toxicology Through Questions, 2017
(b) The enzyme glucose-6-phosphate dehydrogenase is the first enzyme in the pentose phosphate shunt. Some human individuals have a genetically determined deficiency in this enzyme in the red blood cell. The genetic deficiency is sex linked, being only found in males with an especially high incidence in Sephardic Jews from Kurdistan. The enzyme is important as the reaction catalysed produces NADPH which is utilised in various pathways in intermediary metabolism. One of the toxicologically important uses of NADPH is the reduction of oxidised glutathione (GSSG) in the red blood cell. The maintenance of glutathione in the reduced (GSH) state is an important part of cellular protection. Thus GSH will reduce or remove, and thereby detoxify, reactive metabolites of xenobiotics. Those individuals who are deficient in glucose-6-phosphate dehydrogenase have low levels of reduced glutathione in their red blood cells that makes them especially susceptible to drugs which produce metabolites capable of oxidising haemoglobin in the red cell. Drugs such as primaquine and certain sulphonamides will thus cause haemolytic anaemia in susceptible individuals.
The Glutathione Redox State and Zinc Mobilization from Metallothionein and Other Proteins with Zinc–Sulfur Coordination Sites
Christopher A. Shaw in Glutathione in the Nervous System, 2018
One major function of GSH is its reaction with electrophiles that constitute a threat to the cell (Mannervik 1996). This protective action can either be enzyme-catalyzed (e.g., by the glutathione transferase family) or occur nonenzymatically. Another major function is that of a reducing agent. In this reaction, GSH is oxidized to glutathione disulfide (GSSG), also either enzymatically or nonenzymatically. The GSH–GSSG couple is a major determinant of the cellular thiol–disulfide redox state and is controlled by at least two enzymes. Glutathione peroxidases form GSSG from GSH in the presence of peroxides, whereas glutathione reductases regenerate GSH from GSSG in the presence of NADPH. The coupling between the GSH–GSSG and the NADP+–NADPH redox states via glutathione reductase ensures metabolic control through the pentose phosphate pathway and ultimately glucose, since in this pathway glucose 6-phosphate dehydrogenase determines the cellular NADP+/NADPH ratio (Fig. 2). This scheme also illustrates the central role of the GSH–GSSG redox pair in coupling the NADP+–NADPH redox state with other redox pairs, e.g., ascorbate–dehydroascorbate, hydroperoxide–alcohol, and thiol–disulfide. Sufficient reducing power must be available to provide thiolate sulfur for the binding of zinc.
The Pathogenesis and Pathology of the Hemorrhagic State in Viral and Rickettsial Infections
James H. S. Gear in CRC Handbook of Viral and Rickettsial Hemorrhagic Fevers, 2019
In a recently reported case, a 72-year-old man developed fever; hypotension; confusion; choreiform movements; diffuse purpuric eruption of the trunk, proximal extremities, scrotum, and buccal mucosa; and gastrointestinal hemorrhage with guaiac positive stool leading to anemia.139 His laboratory data included platelet count 30,000/μℓ, prolonged prothrombin and partial thromboplastin times, serum fibrinogen 52 mg/dℓ, elevated plasma level of fibrin degradation products, bilirubin 2.3 mg/dℓ, elevated serum concentrations of AST, ALT, LDH, alkaline phosphatase, and creatine Phosphokinase, serum albumin 1.8 g/dℓ, serum creatinine 4.4 mg/dℓ, BUN 91 mg/dℓ, numerous urinary red blood cells, and normal cerebrospinal fluid. Biopsy of the rash revealed vascular injury with intramural and perivascular predominantly mononuclear leukocytes, epithelial necrosis, and numerous immunofluorescent R. mooseri in endothelial cells. Contrary to the published case report, sections examined personally revealed intense congestion, but no thrombosis. An unusually severe case in an American black man with hemolysis and acute renal failure was associated with glucose-6-phosphate dehydrogenase deficiency.140
Erythrocyte G6PD activity and GSH level as risk factors for vascular complications among type 2 diabetics in Osogbo, Nigeria
Published in Alexandria Journal of Medicine, 2019
Glucose-6-phosphate dehydrogenase (G6PD EC 1.1.1.49) enzyme is a rate-limiting/housekeeping cytoplasmic enzyme of the pentose phosphate pathway (PPP) that catalyzes the oxidation of glucose-6-phosphate to 6-phosphogluconolactone and concomitant reduction of NADP+ to nicotinamide adenine dinucleotide (NADPH), which represents the only source of NADPH in erythrocytes [1]. G6PD is widely distributed in many species ranging from prokaryotes to eukaryotes with sequence identity resembling each other, in humans the G6PD encoding gene is located at the telomeric region of the long arm of the X chromosome (band Xq28) with 13 exons, 12 introns, and length of 18kb [2,3]. The polypeptide sequence of the dimer (sometimes tetramer) enzyme with about 515 amino acids contains conserved region of an octapeptide lysine residue (for enzymatic activity), heptapeptide dinucleotide (for binding activity) and a pentapeptide near the substrate binding site. Mutation of the G6PD gene results in protein variants with different levels of enzyme activity and a wide spectrum of biochemical and clinical phenotypes [4,5].
Benzo-a-pyrene-induced reproductive toxicity was abated in rats co-treated with taurine
Published in Toxin Reviews, 2022
Solomon E. Owumi, Opeoluwa Popoola, Moses T. Otunla, Uche A. Okuu, Eseroghene S. Najophe
Homogenized testes and epididymis in 50 mM Tris–HCl buffer (pH 7.4) were centrifuged (12 000 g; 15 min) to obtain the supernatants biochemical assays. Testicular activities of acid phosphatase (ACP) and alkaline phosphatase (ALP) were determined in the testis's supernatant in line with an established method based on hydrolysis p‐nitrophenyl‐phosphate in acid and alkaline medium, respectively (Vanha et al.1973). Glucose‐6‐phosphate dehydrogenase (G6PD) activity was determined using NADP and glucose‐6‐phosphate as substrates in line with Wolf et al. (1987). At the same time, lactate dehydrogenase‐X (LDH‐X) activity was assayed in line with the reported method described by Vassault (1993), which is based on the inter‐conversion of pyruvate and lactate.
Prevalence of G6PD deficiency in Thai blood donors, the characteristics of G6PD deficient blood, and the efficacy of fluorescent spot test to screen for G6PD deficiency in a hospital blood bank setting
Published in Hematology, 2022
Phinyada Rojphoung, Thongbai Rungroung, Usanee Siriboonrit, Sasijit Vejbaesya, Parichart Permpikul, Janejira Kittivorapart
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked inherited disorder that is characterized by the insufficiency of an enzyme that is used in the pentose phosphate pathway to generate nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is a crucial oxidation reduction molecule that protects red blood cells (RBC) from reactive oxygen species (ROS). Patients with G6PD deficiency manifest varying degrees of acute hemolysis in response to oxidative stress precipitated by certain medications and foods. Transfusion of red cell products from G6PD enzyme deficient donors could cause a potentially unfavorable outcome, especially in newborns and those with hemoglobinopathies [1–3]. Current screening criteria of blood donors relative to red cell disorders in Thailand relies mostly on history taking and point-of-care hemoglobin (Hb) testing. The screening of G6PD deficiency is not performed in the donors at the moment. According to the World Health Organization (WHO) Blood Donor Selection guidelines, only donors with a previous history of hemolysis are to be permanently deferred [4]. However, countries with a high prevalence of G6PD deficiency should establish their own criteria for screening at-risk donors, and they should establish their own transfusion guidelines [5].
Related Knowledge Centers
- Catalysis
- Chemical Reaction
- Enzyme
- Metabolic Pathway
- Nicotinamide Adenine Dinucleotide Phosphate
- Pentose Phosphate Pathway
- Red Blood Cell
- Cytosol
- Glucose 6-Phosphate
- 6-Phosphogluconolactone