RESUMO
Cellular energy metabolism is one of the main processes affected during the transition from normal to cancer cells, and it is a crucial determinant of cell proliferation or cell death. As a support for rapid proliferation, cancer cells choose to use glycolysis even in the presence of oxygen (Warburg effect) to fuel macromolecules for the synthesis of nucleotides, fatty acids, and amino acids for the accelerated mitosis, rather than fuel the tricarboxylic acid cycle and oxidative phosphorylation. Mitochondria biogenesis is also reprogrammed in cancer cells, and the destiny of those cells is determined by the balance between energy and macromolecule supplies, and the efficiency of buffering of the cumulative radical oxygen species. In glioblastoma, the most frequent and malignant adult brain tumor, a metabolic shift toward aerobic glycolysis is observed, with regulation by well known genes as integrants of oncogenic pathways such as phosphoinositide 3-kinase/protein kinase, MYC, and hypoxia regulated gene as hypoxia induced factor 1. The expression profile of a set of genes coding for glycolysis and the tricarboxylic acid cycle in glioblastoma cases confirms this metabolic switch. An understanding of how the main metabolic pathways are modified by cancer cells and the interactions between oncogenes and tumor suppressor genes with these pathways may enlighten new strategies in cancer therapy. In the present review, the main metabolic pathways are compared in normal and cancer cells, and key regulations by the main oncogenes and tumor suppressor genes are discussed. Potential therapeutic targets of the cancer energetic metabolism are enumerated, highlighting the astrocytomas, the most common brain cancer.
Assuntos
Humanos , Neoplasias Encefálicas , Glutaminase , Glutamina , Oncogenes/fisiologia , Neoplasias Encefálicas , Proliferação de Células , Transformação Celular Neoplásica , Ciclo do Ácido Cítrico/fisiologia , Glicólise/fisiologia , Via de Pentose Fosfato/fisiologia , Células-Tronco , Células-TroncoRESUMO
Changes in glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GSH-R), reduced glutathione (GSH), glutathione peroxidase (GSH-PO), transketolase (TK) and transaldolase (TA) were studied in lens and red blood cells (RBCs) to understand the possible biochemical mechanisms responsible for the development of senile cataract. The activity of G-6-PD was increased in lens, though not so in erythrocytes during cataractogenesis. A marked decrease was observed in GSH level and GSH-R activity in the lens and RBCs of the cataractous group. The activity of GSH-PO was remarkably high in lens but not in the erythrocytes during the maturity of cataract. The activity of TK decreased gradually in both the lens and erythrocytes. The activity of TA decreased in erythrocytes but increased in the lens with maturation of cataract.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Catarata/sangue , Glutationa/sangue , Glutationa Peroxidase/sangue , Humanos , Cristalino/enzimologia , Pessoa de Meia-Idade , Via de Pentose Fosfato/fisiologiaRESUMO
Distribution of the enzymes of glycolytic and pentose phosphate pathways were studied in cytosolic and leucoplastic fractions of the developing seeds of Brassica. Leucoplasts were isolated using a discontinuous percoll gradient. Intactness of leucoplasts was checked by ADP-glucose pyrophosphorylase assay in presence and absence of triton X-100. No contamination by microbodies, mitochondria and cytosol was observed as assessed by measuring the activities of marker enzymes. The recovery, latency and specific activity of each enzyme in different fractions were compared. The leucoplastic fraction contained complete set of the enzymes of glycolytic and pentose phosphate pathways, indicating that the two subcellular compartments metabolize carbon independently by these pathways. However, the enzymes showed higher activities in cytosolic fraction as compared to those in the leucoplasts, suggesting the need for exchange of metabolites in the two compartments through various translocators, for acting in cooperation to produce energy, reducing power and carbon skeletons for different biosynthetic activities in the non-photosynthetic plastids. Based on these compartmentation studies, a model for carbon flow for fatty acid synthesis in leucoplasts of developing Brassica seeds has been proposed.
Assuntos
Acetatos/metabolismo , Brassica/enzimologia , Metabolismo Energético , Ácidos Graxos/biossíntese , Glucose/metabolismo , Glucose-1-Fosfato Adenililtransferase , Glicólise/fisiologia , Modelos Biológicos , Nucleotidiltransferases/metabolismo , Via de Pentose Fosfato/fisiologia , Sementes/enzimologiaRESUMO
Inhibitory effects of fatty acids and their CoA esters on glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities of human fetal brain cytosol have been studied. Purified human fetal brain fatty acid binding protein reverses the inhibitory effects of palmitoyl-CoA and oleic acid on glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities in human fetal brain cytosol. This protein, when added alone, activates the enzymes. Levels of fatty acid binding proteins as well as the activities of these two HMP shunt pathway enzymes, which provide cofactors like NADPH for reductive biosynthesis, increase with gestation. These results indicate that a relationship exists between the high demand for fatty acids and synthesis of cofactors for lipid biosynthesis in developing brain.