Catecholamine is the common term for the important hormones Norepinephrine (Noradrenaline), Epinephrine (Adrenaline) and Dopamine. Chromaffin cells of the adrenal medulla are the key site of catecholamine synthesis and collections of these cells are also found in heart, liver, kidney, gonads, adrenergic neurons of the postganglionic sympathetic system, and CNS (Central Nervous System). The major product of the adrenal medulla is epinephrine, which constitutes 80% of the catecholamines released from the medulla (Ref.1&2). Tyrosine initiates catecholamine biosynthesis. It is produced in the liver from phenylalanine through the action of phenylalanine hydroxylase. The tyrosine is then transported to catecholamine-secreting neurons where a series of reactions[..]

Iodide, which is ingested in food and water, is actively concentrated by the thyroid gland, converted to organic iodine by TPO (Thyroid Peroxidase also known as Iodide Peroxidase), and incorporated into tyrosine in intrafollicular thyroglobulin within the colloid at the basal cell surface of the thyroid follicular cell. The tyrosines are iodinated at one (Monoiodotyrosine) or two (Diiodotyrosine) sites and then coupled to form two active hormones, Thyroxine (T4, a Tetra-Iodinated Tyrosine derivative) and Triiodothyronine (T3). Unlike the other endocrine hormones, these are not peptides. They are derived from the amino acid tyrosine. T4 is the major active hormone. In tissues outside the thyroid, particularly in the liver and kidney, T4 is converted to T3, an active[..]

Asparagine, a non essential amino acid, synthesized form oxaloacetic acid. It is an amide of a amino acid Aspartate. The enzymes ASPG (asparaginase) and ASRGL1 (asparaginase and isoaspartyl peptidase 1) catalyze the hydrolysis of Asparagine to Aspartate and Ammonia. The enzyme GOT1 (glutamic-oxaloacetic transaminase 1) catalyzes the transamination of Aspartate to oxaloacetic acid which can subsequently enter either the TCA cycle or gluconeogenesis. ASPG play a prominent role in chemotherapy, as cancer cells are dependent on the availability of extracellular Asparagine(Ref.1 &2). Aspartate is converted to Asparagine in an ATP-dependent amidotransferase reaction a[..]

The liver is the major organ responsible for the conversion of excess dietary carbohydrate into triglycerides. Ins (Insulin) and Glucagon (a pancreatic hormone) play critical roles in homeostatsis of Glucose and triglycerides in humans as well as in R. norvegicus (Rattus norvegicus). Glucose serves as a signal independent of hormones in activation of more than 15 enzyme genes in the lipogenic pathways. However, the mechanism by which Glucose generates signal to induce these gene is not known (Ref.1). Ingestion of a high carbohydrate diet leads to the activation of several regulatory enzymes of Glycolysis and Lipogenesis, including the PKLR (Pyruvate Kinase, Liver and RBC), also known as LPK (L-Type Pyruvate Kinase). The lipogenic genes contain ChREs (Carbohydrate[..]

DNA damage checkpoints are critical for preventing tumorigenesis and regulating the response of cells to genotoxic agents. When cells are exposed to DNA damaging agents, they respond by undergoing cell cycle arrest or programmed cell death. 14-3-3 proteins play particularly important roles in coordinating progression of cells through the cell cycle, regulating their response to DNA damage, and influencing life-death decisions following internal injury or external cytokine-mediated cues (Ref.1 and 2). 14-3-3 sigma (also called stratifin or SFN), a tumor suppressor, is a member of a highly conserved family of 14-3-3 proteins that are present in all eukaryotic organisms. Its increased expression causes resistance to anticancer agents and radiation that causes DNA damages[..]

BoNT(Botulinum toxin) is a potent neurotoxin that is produced by the gram-positive, spore-forming, anaerobic bacterium, Clostridum botulinum. There are 7 known immunologically distinct serotypes of BoNT: types A, B, C1, D, E, F, and G. Clostridum neurotoxins are produced as a single inactive polypeptide chain of 150 kDa, which is cleaved by tissue proteinases into an active di-chain molecule: a heavy chain (H) of ~100 kDa and a light chain (L) of ~50 kDa held together by a single disulfide bond. Each serotype demonstrates its own varied mechanisms of action and duration of effect. The heavy chain of each BoNT serotype binds to its specific neuronal ecto-acceptor, whereby, membrane translocation and endocytosis by intracellular synaptic vesicles occurs. The light[..]

The gastrointestinal tract represents an important barrier between human hosts and microbial populations. One potential consequence of host-microbial interactions is the development of mucosal inflammation. A paradigm for such chronic host-microbial relationships is carriage of Helicobacter pylori, Gram-negative bacteria that colonize the stomachs of humans and primates. H. pylori colonization induces chronic gastritis in essentially all hosts, a process that increases the risk of developing peptic ulceration, distal gastric adenocarcinoma, and gastric mucosal lympho-proliferative disease. However, only a small percentage of persons carrying H. pylori develop clinical sequelae; enhanced risk may be related to differences in expression of specific bacterial products, to[..]

Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system that affects both adults and children. MS is characterized by the formation of multiple lesions along the nerve fibers in the brain, spinal cord and optic nerves. Inflammation of the white and gray matter tissues in the CNS due to focal immune cell infiltration and their cytokines are the incipient cause of damage in MS. Hallmark to MS is the demyelinated plaque, which consists of a well-demarcated hypocellular area characterized by the loss of myelin, the formation of astrocytic scars, and the mononuclear cell infiltrates concentrated in perivascular spaces composed of T cells, B lymphocytes, plasma cells, and macrophages. The mechanisms underlying[..]

Rheumatoid arthritis (RA) is a chronic symmetric polyarticular joint disease that primarily affects the small joints of the hands and feet. The inflammatory process is characterized by infiltration of inflammatory cells into the joints, leading to proliferation of synoviocytes and destruction of cartilage and bone.This is a chronic debilitating autoimmune disease of unknown etiology affecting diarthrodial joints. Although the disease is characterized by synovitis of the joints, tendon sheaths, and bursae, manifestations that do not involve the synovium are also frequent (Ref.1 & 2). These articular and systemic manifestations are mediated by hyperplasia of the synovial lining cells and extensive infiltration of macrophages, lymphocytes, fibroblasts, and leukocytes[..]

Blood vessel growth and stability are under the exquisite control of a network of pro- and anti-angiogenic factors. Disruption of the balance between these factors is a characteristic of tumor growth and many vascular diseases. Endogenous angiogenesis inhibitors, particularly those that act broadly at the earliest stages, are excellent pharmacological tools in combating pathogenic vessel growth. PEDF (Pigment Epithelium Derived Factor) is a potent and broadly acting neurotrophic factor that promotes survival of neurons in many regions of the CNS (Central Nervous System) from degeneration caused by serum withdrawal or glutamate cytotoxicity and oxidative damage. Glutamate neurotoxicity involves an increase in intracellular calcium resulting from the opening of NMDA[..]

Various lipid molecules serve as second messengers for transducing signals from the cell surface to the cell interior and trigger specific cellular responses. Sphingolipids represent a complex group of lipids that have recently emerged as new transducers in eukaryotic cells. Sphingolipids are found in all mammalian cells and are mostly located in the plasma membrane. They all contain as a backbone a long-chain base – the sphingoid base (mostly sphingosine) – linked to a fatty acid by an amide bond, thus forming ceramide. Addition of a phosphocholine substituent or sugar to ceramide gives rise to the major sphingolipid SM (sphingomyelin) or to glycosphingolipids, respectively. Ceramide is also produced by breakdown of all sphingolipids by glycosidases (for[..]

Various lipid molecules serve as second messengers for transducing signals from the cell surface to the cell interior and trigger specific cellular responses. Recently, several sphingolipids have emerged as cellular constituents that are able to promote, mediate or counterbalance apoptosis. Sphingolipids are a family of membrane lipids whose structure is made up of a long-chain sphingoid base backbone (such as sphingosine), an amide-linked fatty acid of varying chain and one of various polar head groups (hydroxyl for ceramide, phosphorylcholine for sphingomyelin, and carbohydrate residues for glycosphingolipids). Addition of a phosphocholine substituent or sugar to ceramide gives rise to the major sphingolipid SM (sphingomyelin) or to glycosphingolipids. Ceramide is[..]