Abstract:
:The metabolite 5-aminolevulinic acid (ALA) is an early committed intermediate in the biosynthetic pathway of heme and chlorophyll formation. In plants, 5-aminolevulinic acid is synthesized via a two-step pathway in which glutamyl-tRNA(Glu) is reduced by glutamyl-tRNA(Glu) reductase (GluTR) to glutamate 1-semialdehyde, followed by transformation to 5-aminolevulinic acid catalyzed by glutamate 1-semialdehyde aminotransferase. Using an Escherichia coli cell-based high-throughput assay to screen small molecule libraries, we identified several chemical classes that specifically inhibit heme/chlorophyll biosynthesis at this point by demonstrating that the observed cell growth inhibition is reversed by supplementing the medium with 5-aminolevulinic acid. These compounds were further tested in vitro for inhibition of the purified enzymes GluTR and glutamate 1-semialdehyde aminotransferase as confirmation of the specificity and site of action. Several promising compounds were identified from the high-throughput screen that inhibit GluTR with an I(0.5) of less than 10 microM. Our results demonstrate the efficacy of cell-based high-throughput screening for identifying inhibitors of 5-aminolevulinic acid biosynthesis, thus representing the first report of exogenous inhibitors of this enzyme.
journal_name
Arch Biochem Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Loida PJ,Thompson RL,Walker DM,CaJacob CAdoi
10.1006/abbi.1999.1505subject
Has Abstractpub_date
1999-12-15 00:00:00pages
230-7issue
2eissn
0003-9861issn
1096-0384pii
S0003-9861(99)91505-9journal_volume
372pub_type
杂志文章abstract::A full-length cDNA for human placental thromboxane synthase and a shortened cDNA lacking the sequence corresponding to the N-terminal 2-29 amino acids were expressed in Escherichia coli using a pCW expression vector. Both intact and truncated recombinant enzyme were found in the membrane fraction and were catalyticall...
journal_title:Archives of biochemistry and biophysics
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abstract::Human plasma glutathione peroxidase was purified to homogeneity and partially sequenced. Overlapping peptide fragments from three endopeptidase digests permitted the determination of one sequence of 32 contiguous amino acids and one sequence of 23 contiguous amino acids. Five additional unique peptide sequences withou...
journal_title:Archives of biochemistry and biophysics
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
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journal_title:Archives of biochemistry and biophysics
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abstract::Vitamin D was discovered as an anti-rachitic agent, but even at present, there is no direct evidence to support the concept that vitamin D directly stimulates osteoblastic bone formation and mineralization. It appears to be paradoxical, but vitamin D functions in the process of osteoclastic bone resorption. In 1952, C...
journal_title:Archives of biochemistry and biophysics
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
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pub_type: 杂志文章,评审
doi:10.1016/j.abb.2008.03.015
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abstract::A biochemical basis for the pea and lentil lectin resistance of two Chinese hamster ovary (CHO) cell mutants, Lec13 and Lec13A, was investigated. Studies of the G glycopeptides of vesicular stomatitis virus grown in the mutants indicated that Lec13 cells essentially lack the ability to add fucose to complex carbohydra...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.1996.0547
更新日期:1996-12-01 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.2000.2290
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章,评审
doi:10.1016/j.abb.2012.10.006
更新日期:2013-03-01 00:00:00
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journal_title:Archives of biochemistry and biophysics
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doi:10.1016/0003-9861(85)90178-x
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/j.abb.2010.12.020
更新日期:2011-03-15 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.2001.2676
更新日期:2002-01-15 00:00:00
abstract::Estrogen-induced chick oviduct differentiation is accompanied by an increased capacity for protein glycosylation. A portion of this increase has been attributed to increased levels of dolichyl phosphate (Dol-P). Hormone withdrawal leads to an apparent decrease in Dol-P. Dol-P metabolism in the oviduct has been studied...
journal_title:Archives of biochemistry and biophysics
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journal_title:Archives of biochemistry and biophysics
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journal_title:Archives of biochemistry and biophysics
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
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更新日期:1992-12-01 00:00:00
abstract::To investigate the effect of elevation of liver glycogen synthase (GYS2) activity on glucose and glycogen metabolism, we performed adenoviral overexpression of the mutant GYS2 with six serine-to-alanine substitutions in rat primary hepatocytes. Cell-free assays demonstrated that the serine-to-alanine substitutions cau...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/j.abb.2007.08.006
更新日期:2007-10-15 00:00:00
abstract::A set of membrane proteins from murine myelomonocytic leukemia cell line WEHI-3BD+ was found to be ADP-ribosylated. Both this ADP-ribosylation reaction and granulocytic differentiation in response to recombinant G-CSF were inhibited approximately 50% by 2 mM benzamide, suggesting a correlation between these two proces...
journal_title:Archives of biochemistry and biophysics
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doi:10.1006/abbi.1993.1198
更新日期:1993-04-01 00:00:00
abstract::Providing clean and affordable drinking water without harmful disinfection byproducts generated by conventional chemical disinfectants gives rise to the need for technological innovation. Nanotechnology has great potential in purifying water and wastewater treatment. A graphene oxide-silver (GO-Ag) nanocomposite with ...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/j.abb.2016.04.018
更新日期:2016-08-15 00:00:00
abstract::We hypothesized that cellular oxygen consumption is abnormal during sepsis as a result of increased oxidative stress and selective mitochondrial damage. In a rat model of sepsis (cecal ligation and puncture), we studied the respiratory characteristics of isolated hepatocytes and liver mitochondria 16 h after onset of ...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.1997.0264
更新日期:1997-09-15 00:00:00
abstract::(6R)-5,6,7,8-Tetrahydro-L-biopterin (R-THBP) is a cofactor not only for aromatic amino acid hydroxylases in mammalian tissues but also for nitric oxide synthase (NOS) induced by endotoxins or cytokines in some kinds of cells. Recently it has been reported that nitric oxide (NO) has biological activity in endothelium a...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/0003-9861(92)90472-9
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abstract::A kinetic study of acetaminophen oxidation by tyrosinase in the presence of a physiological nucleophilic agent such as the amino acid L-proline is performed in the present paper. The o-quinone product of the catalytic activity, 4-acetamido-o-benzoquinone, becomes unstable through the chemical addition of L-proline, in...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/s0003-9861(03)00288-1
更新日期:2003-08-15 00:00:00
abstract::HIV-1 trans-activator of transcription (Tat) is an unusual transcriptional activator in being an RNA-binding protein rather than a DNA-binding protein. Recent findings have greatly advanced our understanding of the transcriptional function(s) of this protein. Here we review how Tat interacts with trans-activation resp...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章,评审
doi:10.1006/abbi.1999.1206
更新日期:1999-05-15 00:00:00
abstract::The skeletal system, while characterized by a hard tissue component, is in fact an extraordinarily dynamic system, with disparate functions ranging from structural support, movement and locomotion and soft-organ protection, to the maintenance of calcium homeostasis. Amongst these functions, it has long been known that...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章,评审
doi:10.1016/j.abb.2008.04.001
更新日期:2008-05-15 00:00:00
abstract::The ability of nine phospholipids to alter the activity of low-Km cyclic AMP phosphodiesterase was examined in microsomal fractions of rat adipocytes. The enzyme was activated by phosphatidylserine (21% at 300 microM) and phosphatidylglycerol (36% at 300 microM). The activation was concentration dependent over the ran...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/0003-9861(83)90015-2
更新日期:1983-08-01 00:00:00