Red Cells And Glucose-6-Phosphate Dehydrogenase Deficiency
Ronald L. Nagel in Genetically Abnormal Red Cells, 2019
The major purpose of the hexose monophosphate shunt in red cells seems to be the provision of NADPH which can only be produced in this pathway. The pathway is stimulated by the presence of NADP, and is repressed by, NADPH which predominates in the normal, unstressed erythrocyte. The kinetics of G6PD reactivity are usually reported as fitting Mi-chaelis-Menten type linear kinetic profiles, but have also been described as being nonlinear and sigmoidal, and therefore not suited to Michaelis-Menten equations. This discrepancy has recently been cleared up by Kirkman et al.21,22 who have discovered that most of the intraerythrocytic NADP+ is protein bound — particularly to catalase. When purified G6PD is studied, kinetics are linear; when crude lysates are used under proper conditions, kinetics become complex (sigmoidal) because of the varying ratios of free: bound NADP.
Metabolism
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
Free fatty acid synthesis occurs mainly in the liver and adipose tissue. In the liver, the main precursor for fatty acid synthesis is endogenous glucose derived from glycogen, lactate and blood glucose. Pyruvate is the main source of acetyl CoA, and this process is enhanced by raised plasma insulin concentration and lowered glucagon concentration. Acetyl CoA is an important substrate for the synthesis of free fatty acids under the control of acetyl-CoA-carboxylase. The acetyl CoA is converted first to malonyl CoA and then to fatty acid. Citrate formed in the citric acid cycle diffuses out of the mitochondrion and splits into acetyl CoA and oxaloacetate in the cytoplasm (Figure 65.16). The NADPH required for free fatty acid synthesis is supplied by the hexose monophosphate shunt and by the conversion of citrate to pyruvate in the cytoplasm. The hexose monophosphate shunt is highly active in the cytoplasm of the liver and adipose tissue.
Nutritional Deficiencies
Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw in Hankey's Clinical Neurology, 2020
Thiamine is a cofactor for: Transketolase: This enzyme links glycolysis to the hexose monophosphate shunt (Figure 17.1). The hexose monophosphate shunt is required for the synthesis of: Pentoses (such as ribose phosphate): necessary for the synthesis of nucleotides.Nicotinamide adenine dinucleotide phosphate (NADP): necessary for the synthesis of fatty acids, steroids, and antioxidants.Pyruvate dehydrogenase E1: Pyruvate dehydrogenase is a complex formed by three enzymes (E1, E2, and E3). This complex links the glycolytic pathway with the Krebs cycle. E1 requires thiamine pyrophosphate as a cofactor.Alpha-ketoglutarate dehydrogenase: This enzyme participates in the Krebs' cycle and is involved in the conversion of alpha-ketoglutarate to succinyl-CoA. The deficiencies of this enzyme and E1 lead to decreased adenosine triphosphate (ATP) production and cellular dysfunction.
Modulatory effect of isopulegol on hepatic key enzymes of glucose metabolism in high-fat diet/streptozotocin-induced diabetic rats
Published in Archives of Physiology and Biochemistry, 2021
Karunanithi Kalaivani, Chandrasekaran Sankaranarayanan
Liver is an important organ and plays a major role in maintaining glucose homeostasis by regulating glucose utilization and production. Hexokinase is one of the important key glycolytic and insulin sensitive enzymes (Vats et al. 2003). It catalyses the phosphorylation of glucose to glucose 6-phosphate, thereby channelizing glucose through the glycolytic pathway. The activity of hexokinase was decreased in diabetic rats leading to decreased glucose removal from blood. Pentose phosphate pathway (hexose monophosphate shunt) is an alternative route for the oxidation of glucose (Zhang et al. 2000). This pathway is found in the cytosol is responsible for the biosynthesis of NADPH and ribose-bi-phosphate. NADPH is required for the biosynthesis of glutathione, a non-enzymatic antioxidant. The activity of G6PDH, a rate limiting enzyme of this pathway is greatly decreased in diabetic rats. Administration of isopulegol at the effective dose of 100 mg/kg b.w. increased these enzyme activities thereby improving glucose utilization and oxidation. Our results are in line with Kurup et al. who reported that Averrhoa bilimbi ameliorated glycolytic enzymes in STZ-induced diabetic rats (Kurup and SM 2017).
In vivo evaluation of electron mediators for the reduction of methemoglobin encapsulated in liposomes using electron energies produced by red blood cell glycolysis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Semhar Ghirmai, Leif Bülow, Hiromi Sakai
In red blood cells (RBCs), ferric metHb is mainly reduced by NADH-cytochrome b5 reductase via cytochrome b5, NADPH metHb reductase and NADPH-flavin reductase. According to a simulation study of metHb reduction, the NADPH-flavin pathway is used under normal physiological conditions where the oxidative stress is low and metHb levels are low. Conversely, the NADH-cytochrome b5 pathway plays a major role when oxidative stress is high [11]. These electron-energy-rich molecules are re-energized repeatedly during the glycolysis of RBCs. Glucose, the main energy source for the cells, is metabolized through glycolysis and the hexose monophosphate shunt (HMP), also known as the pentose phosphate pathway [12,13]. In the presence of metHb, the electron-energy-rich molecule NADH produced in the Embden–Meyerhof pathway can be a resource to reduce metHb by NADP-cytochrome b5 to its functional form. The HMP shunt, the only source for NADPH, is generated by reduction of NADP+ [11,14].
Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors
Published in Drug Delivery, 2021
Xianhu Zeng, Zhipeng Li, Chunrong Zhu, Lisa Xu, Yong Sun, Shangcong Han
The pentose phosphate pathway (PPP), also known as the hexose monophosphate bypass or phosphogluconate pathway, branches off from glycolysis when the first step is completed (Stincone et al. 2015). Under the catalysis of hexokinase, glucose-6-phosphate (G6P) is consumed as a main substrate. The PPP assists glycolytic cancer cells so that their anabolic needs are met and they are resistant to oxidative stress. Recently, it has been shown that some neoplastic lesions developed and then promoted the flux of glucose to the PPP (Patra & Hay 2014). Glucose-6-phosphate dehydrogenase (G6PD) regulates the rate of the PPP by catalyzing an irreversible step. The expression level of G6PD is different in various breast cancer subtypes, and is positively correlated with poor prognosis of patients (Pu et al. 2015).
Related Knowledge Centers
- Anabolism
- Glucose
- Metabolic Pathway
- Nicotinamide Adenine Dinucleotide Phosphate
- Nucleotide
- Catabolism
- Glycolysis
- Carbon
- Sugar
- Ribose 5-Phosphate