e-book Glutamine: Metabolism, Enzymology, and Regulation: Metabolism, Enzymology and Regulation

Free download. Book file PDF easily for everyone and every device. You can download and read online Glutamine: Metabolism, Enzymology, and Regulation: Metabolism, Enzymology and Regulation file PDF Book only if you are registered here. And also you can download or read online all Book PDF file that related with Glutamine: Metabolism, Enzymology, and Regulation: Metabolism, Enzymology and Regulation book. Happy reading Glutamine: Metabolism, Enzymology, and Regulation: Metabolism, Enzymology and Regulation Bookeveryone. Download file Free Book PDF Glutamine: Metabolism, Enzymology, and Regulation: Metabolism, Enzymology and Regulation at Complete PDF Library. This Book have some digital formats such us :paperbook, ebook, kindle, epub, fb2 and another formats. Here is The CompletePDF Book Library. It's free to register here to get Book file PDF Glutamine: Metabolism, Enzymology, and Regulation: Metabolism, Enzymology and Regulation Pocket Guide.
Glutamine: Metabolism, Enzymology, and Regulation presents significant contributions on the metabolism, enzymology, and regulation of glutamine of microorganisms to higher animals.
Table of contents

• Glutamine synthetase
• Navigation menu
• Nitrogen Metabolism and the Urea Cycle
• NRF2 Rewires Cellular Metabolism to Support the Antioxidant Response

GS is subject to completely different regulatory mechanisms in cyanobacteria. NsiR4 expression is under positive control of the nitrogen control transcription factor NtcA.

From Wikipedia, the free encyclopedia. Cation binding sites are yellow and orange; ADP is pink; phosphinothricin is blue. Cold Spring Harb. Protein Sci. Biochim Biophys Acta. Biochemistry 6th ed. San Francisco: W. Molecule of the month. Retrieved J Mol Biol. Arch Biochem Biophys.

• Residential Tourism: (De)Constructing Paradise (Tourism and Cultural Change);
• The Bride of the Unicorn (Mills & Boon M&B).
• Structural Biochemistry/Enzyme Regulation/Adenylation - Wikibooks, open books for an open world.
• Glutamine Metabolism.
• Glutamine metabolism in cancer therapy.
• NRF2 Rewires Cellular Metabolism to Support the Antioxidant Response!
• Selected Reviews:.

March Archived from the original on Molecular Genetics and Genomics. Biochemistry 6th Edition. United States of America: Cengage Learning. Microbiological Reviews. Molecular Microbiology. Journal of Bacteriology. PCC ". Nucleic Acids Research.

Metabolism : Protein metabolism , synthesis and catabolism enzymes. Essential amino acids are in Capitals. Saccharopine dehydrogenase Glutaryl-CoA dehydrogenase. Alanine transaminase. D-cysteine desulfhydrase. L-threonine dehydrogenase. Histidine ammonia-lyase Urocanate hydratase Formiminotransferase cyclodeaminase. Ornithine aminotransferase Ornithine decarboxylase Agmatinase.

Glutamate dehydrogenase. Branched-chain amino acid aminotransferase Branched-chain alpha-keto acid dehydrogenase complex Enoyl-CoA hydratase 3-hydroxyisobutyryl-CoA hydrolase 3-hydroxyisobutyrate dehydrogenase Methylmalonate semialdehyde dehydrogenase. Branched-chain amino acid aminotransferase Branched-chain alpha-keto acid dehydrogenase complex 3-hydroxymethylbutyryl-CoA dehydrogenase. Threonine aldolase. Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator. EC number Enzyme superfamily Enzyme family List of enzymes. Glutamate metabolism and transport modulators.

Biology portal. Categories : Genes on human chromosome 1 EC 6. Hidden categories: Protein pages needing a picture.

Navigation menu

Namespaces Article Talk. Views Read Edit View history. The inhibition of LDH suppresses tumor progression of lymphomas and pancreatic cancer xenografts The Krebs cycle the citric acid cycle or the TCA is a series of chemical reactions that generate energy via the oxidation of pyruvate Fig. TCA cycles occur in all aerobic living organisms.

The TCA cycle is the central metabolic hub of the cell that occurs primarily in the mitochondria in contrast to glycolysis, which occurs in the cytosol. Even a minor alteration in these processes markedly influences mitochondrial energy production. Although mutations in mitochondrial DNA have been evaluated for over two decades 37 — 39 , much attention has been focused on the identification of mutations in various TCA cycle enzymes 40 , The cycle consists of eight steps catalyzed by eight different enzymes. Mutations in genes that encode enzymes aconitase, isocitrate dehydrogenase IDH , succinate dehydrogenase SDH , and fumarate hydratase FH may lead to cancer.

Aconitase catalyzes isomerization of citrate to isocitrate via cis-aconitase. Altered expression levels of aconitase are implicated in human prostate cancer, wherein the normal citrate-producing glandular secretory epithelial cells undergo a metabolic transformation to malignant citrate-oxidizing cells, leading to abnormal citrate metabolism and prostate malignancy Glioblastoma multiforme, one of the most common and lethal types of brain cancer, is characterized by IDH1 gene mutations FH is the enzyme that converts fumarate to malate, and mutations in the FH gene are associated with cutaneous, uterine and aggressive forms of renal cancer 46 — Cancer cells that harbor FH mutations produce up to fold more fumarate, and seven-fold more succinate, but decreased levels of citrate and malate FH deficiency in tumor cells alters redox homeostasis to promote tumorigenesis Mutations in the enzyme SDH, which catalyzes the oxidation of succinate to fumarate, are implicated in pheochromocytoma, paraganglioma, renal cell carcinoma and papillary thyroid cancers 50 — Reduced expression and loss of heterozygosity of the SDH gene are observed in gastric and colon carcinoma SDH downregulation results in succinate accumulation leading to transmission of an oncogenic signal from mitochondria to the cytosol Krebs cycle.

The TCA is comprised of series of enzyme-catalyzed reactions, located in the mitochondrial matrix. The PPP, which branches out from glycolysis at the first committed step is the major catabolic pathway of glucose for nucleotide synthesis in cancer cells 55 — The conversion of glucose to G6P, which is catalyzed by the enzyme HK, is a common precursor for various metabolic glucose-consuming routes Fig.

1. BENGALI CUISINE - SIMPLY HOME MADE?
2. 6.5: Amino Acids and the Urea Cycle.
3. Featured Articles;
4. Indian Fights and Fighters: The Soldier and the Sioux.
5. Amino acid metabolism.
6. Hamlet and Love Labours lost: Color Illustrated, Formatted for E-Readers (Unabridged Version)?
7. Oncotarget | Maximizing research impact via insightful peer-review.

Through this pathway, cancer cells produce large quantities of ribose-5 phosphate a precursor for nucleotide synthesis and NAPDH a cofactor used in anabolic reactions. PPP runs parallel to glycolysis and activation of these signaling pathways is a common hallmark of tumor cells 58 , As cancer cells are rapidly dividing, the cells require a constant supply of nucleotides, and the majority of the pentose phosphates are derived from the PPP. Thus, PPP may influence the glycolytic flux. Various enzymes that execute the PPP are implicated in different types of cancer.

Elevated levels of G6PD in association with higher levels of PPP-derived metabolites are responsible for clear-cell renal carcinoma-associated metabolic alterations The same group also demonstrates that simultaneous inhibition of glycolysis and PPP using 2-deoxy-d-glucose and 6-aminonicotinamide, respectively, induces oxidative stress and sensitizes malignant human cancer cell lines to radiotherapy, presumably via the induction of multiple cell death modalities, including apoptosis, necrosis and mitotic catastrophe The next enzyme that has a role in cancer is 6-phosphogluconate dehydrogenase 6PGDH.

Ribulose-5 phosphate isomerase, another critical enzyme in the PPP, which catalyzes the conversion of ribulose-5 phosphate to ribose-5 phosphate and xylulose-5 phosphate Xu5P , is also associated with cancer Ribose-5 phosphate is important as it is a precursor for de novo nucleotide synthesis in rapidly proliferating cancer cells. Thus, all of these studies implicate that the regulation of PPP is vital for cancer cell survival and proliferation. Furthermore, increased glycolytic flux in cancer cells may be regulated directly or indirectly by PPP, and hence, this may represent a promising strategy for treatment of cancer cells.

PPP, which branches out from glycolysis at the first committed stage of glucose metabolism, is required for nucleotide synthesis in cancer cells. Numerous enzymes of the PPP are associated with various types of cancer. Amino acids are one of the major fuels for biosynthetic reactions Fig.

NRF2 Rewires Cellular Metabolism to Support the Antioxidant Response

Amino acids are of utmost necessity for cancer cell proliferation, as they are the major source of nutrients. Even a slight alteration in the biosynthetic pathways may have an impact on amino acid synthesis. Despite glutamine being a nonessential amino acid, it is one of the major fuels for cancer cells 65 — In cancer cells, glutamine is a primary mitochondrial substrate required to maintain mitochondrial membrane potential, integrity and for NADPH production Glutamine catabolism or glutaminolysis is elevated in certain types of tumor 68 — Enzyme glutaminase converts glutamine to glutamate and ammonia.

Glutamine is also involved in activating mechanistic target of rapamycin complex 1 68 , Glycine, another nonessential and one of the simplest amino acids, has also been implicated in cancer 73 , Glycine is a significant constituent of proteins in the body, which build tissues and organs. It is the most abundant type of amino acid in the body and one of the most important regulators of inflammation 75 — Glycine metabolism has also been demonstrated to be upregulated in non-small cell lung cancers 74 , Studies have demonstrated that glycine stimulates proliferation of tumor cells, and cancer cells deprived of glycine indicated a significant reduction in cell growth 74 , Serine, another important nonessential amino acid that participates in nucleotide synthesis, has been shown to be upregulated in breast cancer 74 , Studies using melanoma cells have demonstrated that significant portions of serine are converted to glycine Serine, glycine, and folate vitamin B9 are constitutively active in various tumor cells 74 , 79 , The role of lipid metabolism in cancer cells has long been disregarded; over the past decade, the increased rate of lipid metabolism in cancer cells is being recognized as the prominent hallmark of transformed cells 83 — Lipids are a diverse group of molecules composed of fat, triglycerides, phospholipid, cholesterols and cholesterol esters Fig.

Lipids form the major component of cell membranes phospholipid bilayer , hormones steroid hormones, such as cholesterol and certain lipid-soluble vitamins. Hence, lipids perform various roles in the body, from providing energy to muscles to producing hormones In rapidly proliferating cancer cells, there is an overwhelming requirement for macromolecule synthesis. Hence, cancer cells also demonstrate a high dependence on lipids ACLY catalyzes the conversion of mitochondrial-derived citrate to oxaloacetate and cytosolic acetyl-CoA.

Studies have demonstrated that higher expression levels of ACLY correlated with advanced stages of cancer and lymph node metastasis in tissue samples from gastric adenocarcinoma patients However, targeting ACLY by microRNA miR suppresses cancer cell proliferation and invasion in osteosarcoma, prostate, cervical and lung cancer cells Another study demonstrates that ACLY is required for low molecular weight isoform of cyclin E mediated transformation, migration, and invasion of breast cancer cells in vitro along with tumor growth in vivo In patients with squamous cell carcinoma of the head and neck, there is an association between phosphorylated AMP-activated protein kinase and ACC expression, and the therapeutic outcome is that high phosphorylated-ACC expression is associated with a worse overall survival rate in the patients Similarly, ACC1 expression is upregulated in patients with hepatocellular carcinoma HCC , and upregulation of ACC1 is also significantly correlated with the poorer overall survival of, and disease recurrence in HCC patients Fatty acid synthase FASN , which catalyzes the final step in fatty acid synthesis, is often overexpressed in human cancers 93 , In contrast to enhanced fatty acid synthesis, certain types of cancer rely on the mitochondrial fatty acid oxidation FAO for ATP production The FAO contributes to maintenance of redox homeostasis, and cell survival in hematopoietic stem cells and leukemia cells Carnitine palmitoyltransferase CPT1 , the enzyme that catalyzes the initial step of FAO, is implicated in various types of cancer 96 , 98 , Lipid metabolism.

The interactions between glycolysis, Krebs cycle and lipid metabolism. Lipogenesis is the formation of lipids, whereas lipolysis is the breakdown of lipids. Triglycerides are made up of glycerol and fatty acids. Increased glycose consumption, lactate production, PPP, lipid metabolism, and amino acid synthesis are commonly observed metabolic profile in almost all types of cancer cell. This type of metabolic profiling of tumor cells has been proposed to support their rapid cell growth High rates of glycolysis leading to lactate production aerobic glycolysis or the Warburg effect distinguish cancer cells from normal cells 12 , Glucose is a remarkable fuel for cancer cell, and a precursor for the supply of various metabolic intermediates, which are utilized for lipid, amino acid and nucleotide synthesis.

Glutamine serves as another important source of fuel in cancer cells Glutamine enters the mitochondria to replenish the Krebs cycle intermediates 66 — Highly proliferative cancer cells have a high demand for the rapid synthesis of lipids, amino acids and nucleotides 83 — Tumor cells also divert carbon from glycolysis into the PPP 58 , by which cancer cells synthesize macromolecules, such as nucleic acids.

In addition, citrate and acetyl-coA are key intermediates for lipid synthesis 88 — Since these metabolic pathways are interconnected, understanding the mechanism s leading to this metabolic switch in cancer cells is of utmost importance. Mitochondrial metabolism has emerged as a key target for cancer therapy 8 , 9.

Mitochondria are important bioenergetics and biosynthetic organelles, responsible for producing ATP and various intermediates required for macromolecule synthesis. In addition to participating in energy metabolism, mitochondria participate in calcium homeostasis, production of reactive oxygen species ROS , regulation of apoptosis and cell signaling pathways 3 — 6. Cancer cells have been shown to exhibit various degrees of mitochondrial abnormalities, which render mitochondria a suitable target for anti-cancer drugs 7 — 9.

Mutations in mitochondrial DNA- and nuclear DNA-encoded mitochondrial genes have been observed in various types of human cancer — Furthermore, as mitochondria are the primary source of ROS generation, mitochondrial DNA is continuously exposed to oxidative stress and damage. A previous study investigated the contributions of mitochondrial mutations to tumor cell proliferation and metastasis With increasing mutations, mitochondrial respiratory capacity has been shown to decrease progressively , In addition, defects in the mitochondrial respiratory chain may either promote or inhibit apoptosis Programmed cell death or apoptosis is a complex signaling cascade, which is tightly regulated by proteases, termed caspases.

Initiation of apoptosis and ROS production are closely associated with mitochondria Osellame et al , demonstrated that loss of mitochondrial outer membrane permeability is characteristic of intrinsic apoptosis. In addition, ROS may mediate pro- and anti-apoptotic effects During the last decade, the implication of polyamines in initiation of apoptosis has been the focus of investigations , Novel interactions between polyamine and mitochondria have recently been summarized in a review by Grancara et al There is increasing interest in understanding multiple facets of mitochondrial biology that contribute to cancer.

Mitochondria act as a central hub for cell survival, cell metabolism and cell death pathways. Taking into consideration the multifaceted role of mitochondria in tumorigenesis, targeting mitochondria may present an effective approach to treating cancer.