Metabolic process

Quantifying the multiple processes which control and modulate the extent of oral bioavailability for drug candidates is critical to accurate projection of human pharmacokinetics (PK). Understanding how gut wall metabolism and hepatic elimination factor into first-pass clearance of drugs has improved enormously. Typically, the cytochrome P450s, uridine 5′- diphosphate-glucuronosyltransferases and sulfotransferases, are the main enzyme classes responsible for drug metabolism. Knowledge of the isoforms functionally expressed within organs of first-pass clearance, their anatomical topology (e.

16p caothientrangnguyen 09-05-2020 20 1   Download

DNA of prokaryotes is in a nonequilibrium structural state, characterized as ÔactiveÕ DNA supercoiling. Alterations in this state a€ect many life processes and a homeostatic control of DNA supercoiling has been suggested [Menzel, R. & Gellert, M. (1983) Cell 34, 105±113]. We here report on a new method for quantifying homeostatic control of the high-energy state of in vivo DNA. The method involves making small perturbation in the expression of topoisomerase I, and measuring the e€ect on DNA supercoiling of a reporter plasmid and on the expression of DNA gyrase....

8p system191 01-06-2013 38 5   Download

Department of Medical Biochemistry and Biology, University of Bari, Italy; 2Department of Zoology, Laboratory of Histology and Comparative Anatomy, University of Bari, Italy; 3Center for the Study of Mitochondria and Energy Metabolism (CNR) Bari, Italy Mitochondrial bioenergetic impairment has been found in the organelles isolated from rat liver during the prereplicative phase of liver regeneration.

9p system191 01-06-2013 36 4   Download

A severe challenge to the idea that mitochondrial DNA mutations play a major role in the aging process in mammals is that clear loss-of-function mutations accumulate only to very low levels (under 1% of total) in almost any tissue, even by very old age. Their accumulation is punctate: some cells become nearly devoid of wild-type mitochondrial DNA and exhibit no activity for the partly mitochondrially encoded enzyme cytochrome c oxidase. Such cells accumulate in number with aging, suggesting that they survive indefinitely, which is itself paradoxical....

7p research12 01-06-2013 28 3   Download

Biosynthesis of cholesterol represents one of the funda-mental cellular metabolic processes. SterolD14-reductase (D14-SR) is a microsomal enzyme involved in the con-version of lanosterol to cholesterol in mammals. Amino-acid sequence analysis of a 38-kDa protein puri®ed from bovine liver in our laboratory revealed 90% similarity with a human sterol reductase, SR-1, encoded by the TM7SF2gene, and with the C-terminal domain of human lamin B receptor.

8p research12 29-04-2013 39 3   Download

Metabolite channelling, the process in which consecutive enzymes have confined substrate transfer in metabolic pathways, has been proposed as a biochemical mechanism that has evolved because it enhances catalytic rates and protects unstable intermediates. Results from experiments on the synthesis of radioactive urea [Cheung, C., Cohen, N.S. & Raijman, L (1989)J. Biol. Chem.264, 4038–4044] have been interpreted as implying channelling of arginine between argininosuccinate lyase and arginase in permeabi-lized hepatocytes. ...

9p tumor12 20-04-2013 35 1   Download

Metabolically unstable proteins are involved in a multitude of regulatory networks, including those that control cell signaling, the cell cycle and in many responses to physiological stress. In the present study, we have deter-mined the stability and characterized the degradation process of some members of the Gq class of heterotrimeric G proteins. Pulse-chase experi-ments in HEK293 cells indicated a rapid turnover of endogenously expressed Gaq and overexpressed Gaq and Ga16 subunits.

13p fptmusic 12-04-2013 39 2   Download

Calcium metabolism in oysters is a very complicated and highly controlled physiological and biochemical process. However, the regulation of calcium metabolism in oyster is poorly understood. Our previous study showed that calmodulin (CaM) seemed to play a regulatory role in the process of oyster calcium metabolism. In this study, a full-length cDNA encoding a novel calmodulin-like protein (CaLP) with a long C-terminal sequence was identi-fied from pearl oysterPinctada fucata, expressed in Escherichia coliand characterizedin vitro. ...

12p fptmusic 12-04-2013 41 3   Download

One of the most drastic post-translational modification of proteins in eu-karyotic cells is poly(ADP-ribosyl)ation, catalysed by a family enzymes termed poly(ADP-ribose) polymerases (PARPs). In the human genome, 18 different genes have been identified that all encode PARP family members.

14p fptmusic 11-04-2013 53 2   Download

The effects of pesticide contamination on the metabolism of marine mol-luscs are poorly documented. We investigated the response of a marine bivalve, the Pacific oyster,Crassostrea gigas, using a suppression subtrac-tive hybridization method to identify up- and down-regulated genes after a 30-day exposure period to herbicides (a cocktail of atrazine, diuron and isoproturon, and to the single herbicide glyphosate). A total of 137 unique differentially expressed gene sequences was identified, as well as their asso-ciated physiological process....

14p awards 05-04-2013 48 2   Download

Cellular functions are ultimately linked to metabolic fluxes brought about by thousands of chemical reactions and transport processes. The synthesisof theunderlying enzymes and membrane transporters causes the cell a certain
effort of energyandexternal resources.Considering that those cells should have had a selection advantage during natural evo-lution that enabled them to fulfil vital functions (such as growth, defence against toxic compounds, repair of DNA alterations, etc.)

18p dell39 03-04-2013 34 5   Download

Histidine-containing protein (HPr) is a central metabolic sensor in low-GC Gram-positive bacteria and plays a dual role in sugar uptake by the phos-phoenolpyruvate–sugar phosphotransferase system and in transcriptional control during carbon catabolite repression. The latter process is mediated by interaction between HPr and the carbon catabolite repression master transcription regulator, carbon catabolite protein A (CcpA), a member of the LacI-GalR family of DNA-binding proteins.

11p inspiron33 26-03-2013 50 5   Download

Plants, like many other organisms, have endogenous biological clocks that enable them to organize their physiological, metabolic and developmental processes so that they occur at optimal times. The best studied of these biolo-gical clocks are the circadian systems that regulate daily (24 h) rhythms. At the core of the circadian system in every organism are oscillators respon-sible for generating circadian rhythms.

11p inspiron33 23-03-2013 54 4   Download

Nonenzymatic covalent binding (glycation) of reactive aldehydes (from glu-cose or metabolic processes) to low-density lipoproteins has been previ-ously shown to result in lipid accumulation in a murine macrophage cell line. The formation of such lipid-laden cells is a hallmark of atheroscler-osis.

12p galaxyss3 21-03-2013 52 4   Download

Biological nitrogen fixation is a vital process in the global nitrogen cycle, transforming dinitrogen in the atmosphere into ammonia. Being a very energy-demanding and oxygen-sensitive process, both expression and activity of the nitrogenase enzyme are tightly regu-lated. Rhodospirillum rubrumis a free-living, photosynthetic, purple non-sulfur nitrogen-fixing bacterium, which has been extensively used as a model organism for metabolic and regulatory studies regarding nitrogen fixation.

24p galaxyss3 19-03-2013 66 4   Download

Hepcidin is a liver produced cysteine-rich peptide hormone that acts as the central regulator of body iron metabolism. Hepcidin is synthesized under the form of a precursor, prohepcidin, which is processed to produce the biologically active mature 25 amino acid peptide.

11p galaxyss3 07-03-2013 35 3   Download

Nitric oxide (NO) is a signaling molecule that affects a myriad of processes in plants. However, the mechanistic details are limited. NO post-transla-tionally modifies proteins by S-nitrosylation of cysteines. The soluble S-nitrosoproteome of a medicinal, crassulacean acid metabolism (CAM) plant,Kalanchoe pinnata, was purified using the biotin switch technique.

11p media19 06-03-2013 48 5   Download

The finding of a genome-wide oscillation in transcription that gates cells into S phase and coordinates mitochondrial and metabolic functions has altered our understanding of how the cell cycle is timed and how stable cellular phenotypes are maintained.

13p media19 06-03-2013 37 4   Download

Branched-chain lipids are important components of the human diet and are used as drug molecules, e.g. ibuprofen. Owing to the presence of methyl groups on their carbon chains, they cannot be metabolized in mitochon-dria, and instead are processed and degraded in peroxisomes. Several dif-ferent oxidative degradation pathways for these lipids are known, including a-oxidation, b-oxidation, and x-oxidation.

14p media19 06-03-2013 39 3   Download

Nur77 is one member of the nuclear receptor superfamily. As a transcrip-tion factor, Nur77 participates in a variety of biological processes, includ-ing T cell development, inflammatory responses, steroid hormone synthesis, and hepatic glucose metabolism. It typically acts via binding to the Nur77 responsive element (NBRE) in the promoter regions of its target genes.

14p media19 06-03-2013 48 4   Download