Nuclear Genes in Mitochondrial Function and Biogenesis

University of Arizona, Tucson, Arizona, USA Only a small fraction of the protein constituents of mitochondria are encoded in the small vestigial genome of the organelle. Most of the genes governing the biogenesis of mitochondria reside in the chromosomal DNA of the nucleus. Referred to as PET genes, they represent a sizeable fraction of the total genetic information in the nucleus. PET genes code for the enzymes making up the different metabolic pathways housed in mitochondria, for the...

Nucleolus Overview

University of Massachusetts Medical School, Worcester, Massachusetts, USA Nucleoli are specialized structures within the nuclei of most eukaryotic cells and are the sites of ribosomal RNA synthesis and the assembly of ribosomes. Nucleoli form around the genes for ribosomal RNA (rRNA), and their structural organization is thought to be a manifestation of ongoing rRNA synthesis and ribosome assembly. The nucleoli are not separated from the rest of the nuclear interior by a membrane, and there is...

Neuronal Intermediate Filaments

Columbia University College of Physicians and Surgeons, New York, USA Neuronal intermediate filaments (IFs) are 10-12 nm filaments that are expressed in the nervous system. IF proteins belong to a large gene family and the expression of different IF proteins is tissue specific. In the nervous system, different neuronal IFs are expressed in neuroepithelial stem cells, the central nervous system (CNS) and peripheral nervous system (PNS). In addition, the expression patterns of these neuronal IFs...

Alzheimers Disease AD

AD is a neuro-degenerative disease characterized by the progressive deterioration of higher cognitive functions, including memory loss. Since nicotinic receptors play a critical role in learning and memory, it is not surprising that AD patients lose the cholinergic pathways from the basal forebrain to the hippocampus and the cortex. Moreover, the brains of AD patients have a reduced number of cholinergic cells and presynaptic nAChRs. Since low levels of ACh are believed to lead to the cognitive...

The NPY Y1 Receptor

The NPY Y1 receptor is pharmacologically characterized by its high affinity for Pro34 NPY and D-Arg25 NPY its low affinity for N-terminally truncated NPY analogues and its high affinity for nonpeptide antagonists such as 1229U91, BIBP3226, and BIBO3304 (Table 1, Figure 1). Structurally, the receptor is related to the NPY Y4 and NPY y6 receptors (Figure 2). NPY Y1 receptor mRNA is expressed at highest levels in brain (especially cortex, hippocampus, thalamus, and hypothalamus), vascular smooth...

Neuropeptide Y Receptors

Schering-Plough Research Institute, Kenilworth, New Jersey, USA Neuropeptide Y (NPY) is a 36 amino acid neuropeptide that is widely distributed in both the central and peripheral nervous systems. NPY is a member of the pancreatic poly-peptide family, which also includes the structurally related peptides peptide YY (PYY) and pancreatic polypeptide (PP). Neurons containing NPY typically coexpress and cosecrete classical neurotransmitters and or other neuropeptides (e.g., norepinephrine,...

Relationships Between Disease States and Neurotransmitter Transporters

The ability of the neurotransmitter transporters to regulate normal synaptic signaling implies that functional modification of transporter activity might contribute to the etiology of multiple neurobiological diseases. Indeed, many studies have suggested for years, largely on the basis of pharmacology, that the monoamine transporters NET, DAT, and SERT play an important role in regulating mood, learning, and motor activity, while GABA transporters have been implicated in neuronal excitability...

Nuclear Organization Chromatin Structure and Gene Silencing

Karyopherin

Danzer, Oya Yazgan and Pamela K. Geyer University of Iowa, Iowa City, Iowa, USA Gene silencing is the process whereby a gene is inactivated due to its chromosomal position. Chromosomal rearrangements that move a gene from a transcriptionally permissive location to a transcriptionally nonpermissive location result in gene silencing. This loss of gene expression is not due to a mutation in a gene itself, but due to the placement of a gene into a chromatin environment...

Neurotensin

The discovery of Neurotensin (NT), a 13 aminoacid peptide, occurred during the isolation of another peptide, substance P, from bovine hypothalamus, by Susan Leeman and Robert Carraway in 1973. It was the simple observation of a characteristic vasodilatation occurring around the face and ears after intravenous injection of the isolated material which allowed the purification of NT. Rapidly after its primary structure in aminoacids was known, antibodies were raised, a strategy used for several...

Non Homologous End Joining

The process of DNA non-homologous end joining (NHEJ) is one of several mechanisms that function to repair DNA double strand breaks (DSBs) in DNA. NHEJ represents the major mechanism for DSB repair in G1 phase cells. If unrepaired, a DSB can lead to loss of genomic material which is likely to result in cell death a misrepaired DSB can cause genomic rearrangements, a potential initiating event for carcinogenesis. NHEJ, therefore, represents an important mechanism for maintaining genomic...

Biological Processes Controlled by Nitric Oxide

First defined as EDRF (endothelium-derived relaxing factor), the biological effects of nitric oxide (NO) have now been definitively characterized in a number of tissues. Smooth muscle is often the target of NO action, leading to vasodilation in blood vessels (Figure 1) and penile erection via NO synthesis in the corpus caverno-sum, two well-established functions. Smooth muscle relaxation in the gut is another important function for NO, playing a key role in gastrointestinal tract motility. NO...

Regulation

In 1905 Otto Folin, carrying out experiments on himself and others, described how urea excretion fluctuated with dietary protein, in particular, he showed how it reached a minimum within two days of consuming a zero protein diet. Thus it is clear that flux through the cycle is highly regulated and as with many biochemical pathways, this involves both short-term (changes in enzyme activity with no change in the amount of enzyme) and long-term (changes in the amount of enzyme) mechanisms. The...

Nitric Oxide Signaling

University of California, Berkeley, California, USA The basic components of nitric oxide (NO) signaling involve nitric oxide synthase (NOS) to synthesize NO and the soluble isoform of guanylate cyclase (sGC) to trap NO. Once activated by NO, sGC converts GTP to guanosine 3'5'-cyclic monophosphate (cGMP), leading to cGMP-dependent physiological responses such as vasodilation. Termination of the cGMP signal involves a cyclic nucleotide phosphodiesterase (PDE). There are multiple PDE isoforms, and...

Guanylyl Cyclase Linked Natriuretic Peptide Receptors

The ligand selectivity for NPR-A is ANP > BNP q CNP, whereas the ligand selectivity for NPR-B is CNP q ANP > BNP. Mice lacking NPR-A are hypertensive and develop cardiac hypertrophy and ventricular fibrosis. In addition, they are completely unresponsive to the renal and vasorelaxing effects of ANP and BNP, consistent with NPR-A being the sole signaling receptor for these peptides. A promoter mutation resulting in reduced transcription of the human NPR-A gene was recently identified and...

Oxygenases

Osaka Bioscience Institute, Suita, Osaka, Japan Oxygenases are a group of oxidative enzymes that catalyze the direct addition or fixation of molecular oxygen into various substrates. The terms mono and di oxygenases are generally assigned to the enzymes catalyzing the incorporation of either one or two atoms of oxygen per mole of substrate, respectively. Prior to the discovery of oxygenases in 1955, the essential characteristics of biological oxidation processes was believed to be the removal...

Neurotensin Receptor Implication in Cancer

Increasing evidence demonstrates that proNT and NTS1 are deregulated in several human cancers such as colon, pancreatic, prostate, and lung cancer, suggesting that NT may exert an autocrine activation of its own NTS1 receptor in cancer. Thus, the use of NT receptor antagonists to block the proliferative effect of NT on cancer cells is one of the promising prospects in cancer therapy. In this respect, it has been recently reported that SR 48692 could inhibit NT-stimulated growth of human colon,...

Pentose Phosphate Pathway History of

Australian National University, Canberra, Australia In this article the oxidative and non-oxidative segments of the pentose pathway (PP) of glucose metabolism are defined. The discovery in 1931-1935 by the German biochemist, Otto Warburg, of the oxidative division of the pathway and of the chemistry and role of a new pyridine nucleotide co-enzyme in its reactions is deliniated. The successful revelation of many of the reactants and enzymes of the non-oxidative PP was largely achieved by two...

Nitric Oxide Synthase

The catalytic activity of the NOS isoforms (constitutive) involved in signaling is controlled by Ca2+ and calmodulin (CaM). After stimulation by the appropriate external signal, an increase in intracellular-free Ca2+ occurs, which then leads to a Ca2+ -calmodulin complex. Each of the four EF hands of calmodulin binds one Ca2+, and then this Ca2+ -CaM complex binds to NOS, thereby activating NOS to synthesize NO. The NOS reaction is shown in Figure 2. The enzyme converts L-arginine to citrulline...

Neurotensin Receptor Implication in Brain Functions

Neurotensin and Dopamine Interaction More than twenty years ago, it was observed that some behavioral and biochemical effects of centrally administered NT were similar to those exhibited by antipsycho-tic drugs, and that these drugs stimulated NT expression in brain regions where there are mesocorticolimbic and nigrostriatal DA neuronal projections. These observations led to the hypothesis that NT may act as an endogenous neuroleptic, and stimulated the research on NT-DA interactions. Moreover,...

P70 S6 Kinase

This family of enzymes phosphorylates a series of seryl residues in the C-terminus of S6. It was identified in the 1980s following early work showing that insulin, and a range of other stimuli, led to increased phosphorylation of S6. The p70 S6 kinases were some of the earliest insulin- and mitogen-stimulated kinases to be studied in any detail, largely because the relatively high abundance of S6 means that it appears as a major insulin-stimulated phosphoprotein. p70 S6 kinases are now believed...

Cps

FIGURE 4 Extrahepatic arginine synthesis. ASL, argininosuccinate lyase, ASS, argininosuccinate synthetase, CPS 1, carbamoyl phosphate synthetase 1, OTC, ornithine transcarbomylase, OAT, ornithine aminotransferase, P5C, pyrroline 5-carboxylate. but the very high arginase activity of the liver means that both dietary arginine and arginine synthesized within the liver are rapidly hydrolyzed and not available to the body. Thus the arginine required for the synthesis of protein, nitric oxide,...

Ornithine Cycle

Ornithine Cycle

Rutgers University, New Brunswick, New Jersey, USA The ornithine cycle, also known as the urea cycle and the Krebs-Henseleit cycle, is the pathway in mammalian liver that allows the detoxification and excretion of excess nitrogen as urea. Flux through the cycle is driven by the demand to remove excess ammonia derived from the degradation of amino acids that arise either from the diet or from endogenous proteolysis. In a healthy individual, consuming a typical western diet, flux through the...

Atrial Natriuretic Peptide

Atrial Natriuretic Peptide Anp

The first natriuretic peptide to be identified was atrial natriuretic peptide (ANP), which was originally called atrial natriuretic factor (ANF) because of its unknown structure. It was discovered by de Bold and co-workers in 1981. They found that intravenous infusion of atrial, but not ventricular, homogenates into rats caused a rapid and dramatic increase in renal sodium and water excretion that was accompanied by reduced blood pressure. Subsequently, a smooth muscle relaxing activity was...