当前位置： SCI文献检索 > BIOCHEMISTRY期刊下所有文献 > Inactivation of N-acyl phosphatidylethanolamine phospholipase D reveals multiple mechanisms for the biosynthesis of endocannabinoids.

Inactivation of N-acyl phosphatidylethanolamine phospholipase D reveals multiple mechanisms for the biosynthesis of endocannabinoids.

Abstract：

:N-Acyl ethanolamines (NAEs) constitute a large and diverse class of signaling lipids that includes the endogenous cannabinoid anandamide. Like other lipid transmitters, NAEs are thought to be biosynthesized and degraded on-demand rather than being stored in vesicles prior to signaling. The identification of enzymes involved in NAE metabolism is therefore imperative to achieve a complete understanding of this lipid signaling system and control it for potential therapeutic gain. Recently, an N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) was identified as a candidate enzyme involved in the biosynthesis of NAEs. Here, we describe the generation and characterization of mice with a targeted disruption in the NAPE-PLD gene [NAPE-PLD(-/-) mice]. Brain tissue from NAPE-PLD(-/-) mice showed more than a 5-fold reduction in the calcium-dependent conversion of NAPEs to NAEs bearing both saturated and polyunsaturated N-acyl chains. However, only the former group of NAEs was decreased in level in NAPE-PLD(-/-) brains, and these reductions were most dramatic for NAEs bearing very long acyl chains (>or=C20). Further studies identified a calcium-independent PLD activity in brains from NAPE-PLD(-/-) mice that accepted multiple NAPEs as substrates, including the anandamide precursor C20:4 NAPE. The illumination of distinct enzymatic pathways for the biosynthesis of long chain saturated and polyunsaturated NAEs suggests a strategy to control the activity of specific subsets of these lipids without globally affecting the function of the NAE family as a whole.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Leung D,Saghatelian A,Simon GM,Cravatt BF

doi

10.1021/bi060163l

subject

Has Abstract

pub_date

2006-04-18 00:00:00

pages

4720-6

issue

15

eissn

0006-2960

issn

1520-4995

journal_volume

45

pub_type

杂志文章

相关文献

BIOCHEMISTRY文献大全
  • Secondary structure in properdin of the complement cascade and related proteins: a study by Fourier transform infrared spectroscopy.

    abstract：:Six structural repeat motifs of 58 amino acids are found in the sequence of both mouse and human properdins. Twelve more examples of the motif are available from the sequences of thrombospondin, the terminal complement components, and the thrombospondin-related anonymous protein. The averaged Robson and Chou-Fasman se...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00444a007

    authors： Perkins SJ,Nealis AS,Haris PI,Chapman D,Goundis D,Reid KB

    更新日期：1989-09-05 00:00:00

  • Laminins and other strange proteins.

    abstract：:Laminins are large multidomain proteins of the extracellular matrix (ECM) with important functions in the development and maintenance of cellular organization and supramolecular structure, in particular in basement membranes. Each molecule is composed of three polypeptide chains, A (300-400 kDa) and B1 and B2 (180-200...

    journal_title：Biochemistry

    pub_type： 杂志文章,评审

    doi：10.1021/bi00159a001

    authors： Engel J

    更新日期：1992-11-10 00:00:00

  • 4-Azido-2-nitrophenyl phosphate, a new photoaffinity derivative of inorganic phosphate. Study of its interaction with the inorganic phosphate binding site of beef heart mitochondrial adenosine triphosphatase.

    abstract：:4-Azido-2-nitrophenyl phosphate (ANPP) was synthesized and characterized. ANPP, unlabeled or labeled by 32P, was used as a photoreactive analogue of Pi to study the Pi binding site(s) in isolated F1-ATPase and inside-out particles from beef heart mitochondria. In the dark, the phosphate bond of ANPP was cleaved by alk...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00561a013

    authors： Lauquin G,Pougeois R,Vignais PV

    更新日期：1980-09-30 00:00:00

  • Primary structure of human J chain: alignment of peptides from chemical and enzymatic hydrolyses.

    abstract：:The primary structure of the J chain from a human Waldenströms IgM protein has been determined using a combination of automated and conventional Edman degradative procedures. Eighty-five percent of the sequence was established with peptides isolated from tryptic digests of carboxyamidomethylated and citraconylated J c...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00635a002

    authors： Mole JE,Bhown AS,Bennett JC

    更新日期：1977-08-09 00:00:00

  • Lysine Side-Chain Dynamics in the Binding Site of Homeodomain/DNA Complexes As Observed by NMR Relaxation Experiments and Molecular Dynamics Simulations.

    abstract：:An important but poorly characterized contribution to the thermodynamics of protein-DNA interactions is the loss of entropy that occurs from restricting the conformational freedom of amino acid side chains. The effect of restricting the flexibility of several side chains at a protein-DNA interface may be comparable in...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/acs.biochem.8b00195

    authors： Baird-Titus JM,Thapa M,Doerdelmann T,Combs KA,Rance M

    更新日期：2018-05-15 00:00:00

  • Arginine 177 is involved in Mn(II) binding by manganese peroxidase.

    abstract：:Site-directed mutations R177A and R177K in the gene encoding manganese peroxidase isozyme 1 (mnp1) from Phanerochaete chrysosporium were generated. The mutant enzymes were expressed in P. chrysosporium during primary metabolic growth under the control of the glyceraldehyde-3-phosphate dehydrogenase gene promoter, puri...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi990943c

    authors： Sollewijn Gelpke MD,Moënne-Loccoz P,Gold MH

    更新日期：1999-08-31 00:00:00

  • An extracellular loop region of the serotonin transporter may be involved in the translocation mechanism.

    abstract：:The serotonin transporter (SERT) is a member of a highly homologous family of proteins responsible for the reuptake of biogenic amines from the synaptic cleft. We took advantage of native restriction sites in SERT to construct a chimeric transporter containing a small (34 amino acid) region of the norepinephrine trans...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi962150l

    authors： Stephan MM,Chen MA,Penado KM,Rudnick G

    更新日期：1997-02-11 00:00:00

  • Prothrombin domains: circular dichroic evidence for a lack of cooperativity.

    abstract：:The far-ultraviolet circular dichroism spectra of bovine and human prothrombin, prothrombin fragment 1, prethrombin 1, prothrombin fragment 2, and prethrombin 2 (prethrombin 2des(1--13)) were determined and the method of Chen et al. [Chen, Y. H., Yang, J. T., & Martinez, H. M. (1972) Biochemistry 11, 4120--4131; Chen,...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00577a017

    authors： Bloom JW,Mann KG

    更新日期：1979-05-15 00:00:00

  • Spin equilibrium in human methemoglobin: effects of inositol hexaphosphate and bezafibrate as measured by resonance Raman spectroscopy.

    abstract：:The spin equilibria of several derivatives of human methemoglobin were probed by resonance Raman scattering. The intensity of lines in the Raman spectrum gives a measure of the high-spin (S = 5/2) to low-spin (S = 1/2) ratio which agrees well with the spin equilibria determined from direct magnetic susceptibility meas...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00438a056

    authors： Noble RW,DeYoung A,Rousseau DL

    更新日期：1989-06-13 00:00:00

  • Phase transitions of the purple membranes of Halobacterium halobium.

    abstract：:Purple membranes of Halobacterium halobium were studied by differential scanning calorimetry. No transition was detected at temperatures below 70 degrees C. A small endothermic transition was seen at about 80 degrees C and a larger one at 100 degrees C. The larger transition is the irreversible denaturation of bacteri...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00598a026

    authors： Jackson MB,Sturtevant JM

    更新日期：1978-03-07 00:00:00

  • Steroid-protein interactions. Human corticosteroid-binding globulin: characterization of dimer and electrophoretic variants.

    abstract：:Human corticosteroid-binding globulin (CBG) forms a dimer that was isolated by gel filtration, has full binding affinity and capacity, and can be dissociated to the monomer. Monomeric CBG consists of two distinct molecular variants, which were detected by polyacrylamide gel electrophoresis in the presence and absence ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00533a010

    authors： Mickelson KE,Harding GB,Forsthoefel M,Westphal U

    更新日期：1982-02-16 00:00:00

  • Poly(pro)II helices in globular proteins: identification and circular dichroic analysis.

    abstract：:A method to identify poly(L-proline)-type (PII) conformation in crystal structures of globular proteins is presented. Short segments of PII structure were identified in globular protein structures, and these form a significant fraction of the residues which are not assigned to alpha-helix, beta-sheet, and beta-turns. ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00199a028

    authors： Sreerama N,Woody RW

    更新日期：1994-08-23 00:00:00

  • Understanding functional divergence in proteins by studying intragenomic homologues.

    abstract：:Studies of intragenomic homologues in bacterial genomes can provide valuable insights into functional divergence. Three GTP cyclohydrolase II homologues in the Streptomyces coelicolor genome have been shown to catalyze two related but distinct reactions [Spoonamore, J. E., Dahlgran, A. L., Jacobsen, N. E., and Bandari...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi702263z

    authors： Spoonamore JE,Bandarian V

    更新日期：2008-02-26 00:00:00

  • Slow rate of phosphodiester bond formation accounts for the strong bias that Taq DNA polymerase shows against 2',3'-dideoxynucleotide terminators.

    abstract：:Taq and T7 DNA polymerases have become basic molecular biology "tools" for DNA sequence analysis. However, Taq, unlike T7 DNA polymerase, is strongly biased against the incorporation of 2',3'-dideoxynucleotide triphosphates (ddNTPs) indicating very different substrate selectivities. Equilibrium binding and rate consta...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi951682j

    authors： Brandis JW,Edwards SG,Johnson KA

    更新日期：1996-02-20 00:00:00

  • Subunits of RNA polymerase in function and structure. 7. Structure of premature core enzyme.

    abstract：:The structure of premature core enzyme, an obligatory intermediate in both in vivo and in vitro assembly of Escherichia coli DNA-dependent RNA polymerase, was compared with that of native core enzyme. Though this assembled but inactive form of core enzyme harbors the gross conformation similar to that of native enzyme...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00573a006

    authors： Ishihama A,Aiba H,Saitoh T,Takahashi S

    更新日期：1979-03-20 00:00:00

  • Localization of the factor IX propeptide binding site on recombinant vitamin K dependent carboxylase using benzoylphenylalanine photoaffinity peptide inactivators.

    abstract：:The propeptide binding/activation site on the vitamin K dependent carboxylase has been localized to a region of carboxylase between residues Arg +50 and Glu +225 by photoinactivation studies using [125I]tyrosyl-labeled benzoylphenylalanine (Bpa)-containing analogs of proFIX19, a peptide containing residues -18 to +1 o...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00002a012

    authors： Yamada M,Kuliopulos A,Nelson NP,Roth DA,Furie B,Furie BC,Walsh CT

    更新日期：1995-01-17 00:00:00

  • Acetylation of lysine 92 improves the chaperone and anti-apoptotic activities of human αB-crystallin.

    abstract：:αB-Crystallin is a chaperone and an anti-apoptotic protein that is strongly expressed in many tissues, including the lens, retina, heart, and kidney. In the human lens, several lysine residues in αB-crystallin are acetylated. We have previously shown that such acetylation is predominant at lysine 92 (K92) and lysine 1...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi400638s

    authors： Nahomi RB,Huang R,Nandi SK,Wang B,Padmanabha S,Santhoshkumar P,Filipek S,Biswas A,Nagaraj RH

    更新日期：2013-11-12 00:00:00

  • Substrate-Induced Facilitated Dissociation of the Competitive Inhibitor from the Active Site of O-Acetyl Serine Sulfhydrylase Reveals a Competitive-Allostery Mechanism.

    abstract：:By classical competitive antagonism, a substrate and competitive inhibitor must bind mutually exclusively to the active site. The competitive inhibition of O-acetyl serine sulfhydrylase (OASS) by the C-terminus of serine acetyltransferase (SAT) presents a paradox, because the C-terminus of SAT binds to the active site...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/acs.biochem.7b00500

    authors： Singh AK,Ekka MK,Kaushik A,Pandya V,Singh RP,Banerjee S,Mittal M,Singh V,Kumaran S

    更新日期：2017-09-19 00:00:00

  • Site-specific chemical labeling of mitochondrial respiratory complex I through ligand-directed tosylate chemistry.

    abstract：:The site-specific chemical modification of NADH-quinone oxidoreductase (complex I) by various functional probes such as fluorophores and microbeads, without affecting the enzyme activity, may allow single-molecule analyses of putative dynamic conformational changes in the enzyme. In an attempt to address this challeng...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi500205x

    authors： Masuya T,Murai M,Ifuku K,Morisaka H,Miyoshi H

    更新日期：2014-04-15 00:00:00

  • Structural determinants of protein dynamics: analysis of 15N NMR relaxation measurements for main-chain and side-chain nuclei of hen egg white lysozyme.

    abstract：:15N-labeled hen lysozyme has been studied by 2D and 3D NMR in order to characterize its dynamic behavior. The resonances of all main-chain amide nitrogen atoms were assigned, as were resonances of nitrogen atoms in 28 side chains. Relaxation measurements for the main-chain and arginine and tryptophan side-chain 15N nu...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00012a023

    authors： Buck M,Boyd J,Redfield C,MacKenzie DA,Jeenes DJ,Archer DB,Dobson CM

    更新日期：1995-03-28 00:00:00

  • Multistep mechanism of codon recognition by transfer ribonucleic acid.

    abstract：:The mechanism of codon recognition by tRNA is investigated in the system tRNAPhe + UUC by temperature-jump measurements using the Wye base fluorescence as a label. In 0.4 M Na+ and 5 mM Mg2+ a two-step reaction is observed and described quantitatively; UUC is shown to bind preferentially to one of two conformations on...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00557a023

    authors： Labuda D,Pörschke D

    更新日期：1980-08-05 00:00:00

  • Phosphorylation modulates keratin structure.

    abstract：:Bovine hoof keratin was shown to be a substrate for cAMP-dependent protein kinase using [gamma-32P]ATP. Natural-abundance cross-polarization (CP) MAS 13C NMR was used to examine the effect of phosphorylation on keratin structure. When short contact times were used, phosphorylation was shown to increase the number of r...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00458a023

    authors： Yeagle PL,Frye J,Eckert BS

    更新日期：1990-02-13 00:00:00

  • Characterization of the N-terminal and C-terminal domains of human apolipoprotein(a): relevance to fibrin binding.

    abstract：:The structural domains of human apolipoprotein(a) (apo(a)) in the lipoprotein(a) (Lp(a)) particle have been recently investigated by limited proteolysis [Huby, T., Doucet, C., Dieplinger, H., Chapman, J., & Thillet, J. (1994) Biochemistry 33, 3335-3341]. We have shown that apo(a) can be cleaved into two structural dom...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00022a011

    authors： Huby T,Schröder W,Doucet C,Chapman J,Thillet J

    更新日期：1995-06-06 00:00:00

  • Identification of peptide antagonists to glycoprotein Ibalpha that selectively inhibit von Willebrand factor dependent platelet aggregation.

    abstract：:GPIbalpha is an integral membrane protein of the GPIb-IX-V complex found on the platelet surface that interacts with the A1 domain of von Willebrand factor (vWF-A1). The interaction of GPIbalpha with vWF-A1 under conditions of high shear stress is the first step in platelet-driven thrombus formation. Phage display was...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi702428q

    authors： Benard SA,Smith TM,Cunningham K,Jacob J,DeSilva T,Lin L,Shaw GD,Kriz R,Kelleher KS

    更新日期：2008-04-22 00:00:00

  • Characterization of prostate-specific antigen proteolytic activity on its major physiological substrate, the sperm motility inhibitor precursor/semenogelin I.

    abstract：:The protease prostate-specific antigen (PSA) is a marker widely used clinically for monitoring prostatic malignancies. Under normal conditions, this enzyme is mainly involved in the post ejaculation degradation of the major human seminal protein, the seminal plasma motility inhibitor precursor/semenogelin I (SPMIP/SgI...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi9626158

    authors： Robert M,Gibbs BF,Jacobson E,Gagnon C

    更新日期：1997-04-01 00:00:00

  • Dynamics of Aromatic Side Chains in the Active Site of FKBP12.

    abstract：:FKBP12, a small human enzyme, aids protein folding by catalyzing cis-trans isomerization of peptidyl-prolyl bonds, and is involved in cell signaling pathways, calcium regulation, and the immune response. The underlying molecular mechanisms are not fully understood, but it is well-known that aromatic residues in the ac...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/acs.biochem.6b01157

    authors： Weininger U,Modig K,Geitner AJ,Schmidpeter PA,Koch JR,Akke M

    更新日期：2017-01-10 00:00:00

  • Inhibition of HIV protease activity by heterodimer formation.

    abstract：:The dimeric nature of the HIV protease has been exploited to devise a novel mode of inhibiting the enzyme. The use of defective monomers or nonidentical subunits to exchange with wild-type homodimers produces catalytically defective heterodimers. Incubation of the HIV1 or HIV2 protease with a 4-fold molar excess of an...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00215a016

    authors： Babé LM,Pichuantes S,Craik CS

    更新日期：1991-01-08 00:00:00

  • Phosphonate analogues of carboxypeptidase A substrates are potent transition-state analogue inhibitors.

    abstract：:Analogues of tri- and tetrapeptide substrates of carboxypeptidase A in which the scissile peptide linkage is replaced with a phosphonate moiety (-PO2--O-) were synthesized and evaluated as inhibitors of the enzyme. The inhibitors terminated with either L-lactate or L-phenyllactate [designated (O) Ala and (O) Phe, resp...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00441a022

    authors： Hanson JE,Kaplan AP,Bartlett PA

    更新日期：1989-07-25 00:00:00

  • Amino-terminal domain of TIF2 is involved in competing for corepressor binding to glucocorticoid and progesterone receptors.

    abstract：:Both agonist- and antagonist-bound glucocorticoid receptors (GRs) and progesterone receptors (PRs) regulate gene transcription with the assistance of corepressors (NCoR and SMRT) and coactivators (TIF2/GRIP1, SRC1, and AIB1). Receptor binding of these cofactors is competitive and is considered to involve interactions ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi7004575

    authors： Wang D,Wang Q,Awasthi S,Simons SS Jr

    更新日期：2007-07-10 00:00:00

  • Two-step purification of the major phosphorylated protein in reticulocyte 40S ribosomal subunits.

    abstract：:In reticulocytes, a single ribosomal protein, S13, has been shown to be phosphorylated by the cAMP-regulated protein kinases. The 40S ribosomal subunits were phosphorylated in vitro with [gamma-32P]ATP to facilitate the identification of S13 during the two-step purification procedure. Total ribosomal protein from the ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00604a003

    authors： Du Vernay VH Jr,Traugh JA

    更新日期：1978-05-30 00:00:00