BioNMR
NMR aggregator & online community since 2003
BioNMR    
Learn or help to learn NMR - get free NMR books!
 

Go Back   BioNMR > Educational resources > Journal club
Advanced Search
Home Forums Wiki NMR feeds Downloads Register Today's Posts



Jobs Groups Conferences Literature Pulse sequences Software forums Programs Sample preps Web resources BioNMR issues


Webservers
NMR processing:
MDD
NMR assignment:
Backbone:
Autoassign
MARS
UNIO Match
PINE
Side-chains:
UNIO ATNOS-Ascan
NOEs:
UNIO ATNOS-Candid
UNIO Candid
ASDP
Structure from NMR restraints:
Ab initio:
GeNMR
Cyana
XPLOR-NIH
ASDP
UNIO ATNOS-Candid
UNIO Candid
Fragment-based:
BMRB CS-Rosetta
Rosetta-NMR (Robetta)
Template-based:
GeNMR
I-TASSER
Refinement:
Amber
Structure from chemical shifts:
Fragment-based:
WeNMR CS-Rosetta
BMRB CS-Rosetta
Homology-based:
CS23D
Simshift
Torsion angles from chemical shifts:
Preditor
TALOS
Promega- Proline
Secondary structure from chemical shifts:
CSI (via RCI server)
TALOS
MICS caps, β-turns
d2D
PECAN
Flexibility from chemical shifts:
RCI
Interactions from chemical shifts:
HADDOCK
Chemical shifts re-referencing:
Shiftcor
UNIO Shiftinspector
LACS
CheckShift
RefDB
NMR model quality:
NOEs, other restraints:
PROSESS
PSVS
RPF scores
iCing
Chemical shifts:
PROSESS
CheShift2
Vasco
iCing
RDCs:
DC
Anisofit
Pseudocontact shifts:
Anisofit
Protein geomtery:
Resolution-by-Proxy
PROSESS
What-If
iCing
PSVS
MolProbity
SAVES2 or SAVES4
Vadar
Prosa
ProQ
MetaMQAPII
PSQS
Eval123D
STAN
Ramachandran Plot
Rampage
ERRAT
Verify_3D
Harmony
Quality Control Check
NMR spectrum prediction:
FANDAS
MestReS
V-NMR
Flexibility from structure:
Backbone S2
Methyl S2
B-factor
Molecular dynamics:
Gromacs
Amber
Antechamber
Chemical shifts prediction:
From structure:
Shiftx2
Sparta+
Camshift
CH3shift- Methyl
ArShift- Aromatic
ShiftS
Proshift
PPM
CheShift-2- Cα
From sequence:
Shifty
Camcoil
Poulsen_rc_CS
Disordered proteins:
MAXOCC
Format conversion & validation:
CCPN
From NMR-STAR 3.1
Validate NMR-STAR 3.1
NMR sample preparation:
Protein disorder:
DisMeta
Protein solubility:
camLILA
ccSOL
Camfold
camGroEL
Zyggregator
Isotope labeling:
UPLABEL
Solid-state NMR:
sedNMR


Reply
 
Thread Tools Search this Thread Rate Thread Display Modes
  #1  
Old 01-09-2013, 10:01 AM
nmrlearner's Avatar
Senior Member
 
Join Date: Jan 2005
Posts: 23,714
Points: 193,617, Level: 100
Points: 193,617, Level: 100 Points: 193,617, Level: 100 Points: 193,617, Level: 100
Level up: 0%, 0 Points needed
Level up: 0% Level up: 0% Level up: 0%
Activity: 50.7%
Activity: 50.7% Activity: 50.7% Activity: 50.7%
Last Achievements
Award-Showcase
NMR Credits: 0
NMR Points: 193,617
Downloads: 0
Uploads: 0
Default NMR Identification of Endogenous Metabolites interacting with Fatted and Non-Fatted Human Serum Albumin in Blood Plasma: Fatty Acids influence the HSA-Metabolite Interaction

NMR Identification of Endogenous Metabolites interacting with Fatted and Non-Fatted Human Serum Albumin in Blood Plasma: Fatty Acids influence the HSA-Metabolite Interaction


Available online 8 January 2013
Publication year: 2013
Source:Journal of Magnetic Resonance



Metabolites and their concentrations are direct reporters on body biochemistry. Thanks to technical developments metabolic profiling of body fluids, such as blood plasma, by for instance NMR has in the past decade become increasingly accurate enabling successful clinical diagnostics. Human Serum Albumin (HSA) is the main plasma protein (~60% of all plasma protein) and responsible for the transport of endogenous (e.g. fatty acids) and exogenous metabolites, which it achieves thanks to its multiple binding sites and its flexibility. HSA has been extensively studied with regard to its binding of drugs (exogenous metabolites), but only to a lesser extent with regard to its binding of endogenous (non-fatty acid) metabolites. To obtain correct NMR measured metabolic profiles of blood plasma and/or potentially extract information on HSA and fatty acids content, it is necessary to characterize these endogenous metabolite/plasma protein interactions. Here, we investigate these metabolite-HSA interactions in blood plasma and blood plasma mimics. The latter contain the roughly twenty metabolites routinely detected by NMR (also most abundant) in normal relative concentrations with fatted or non-fatted HSA added or not. First, we find that chemical shift changes are small and seen only for a few of the metabolites. In contrast, a significant number of the metabolites display reduced resonance integrals and reduced free concentrations in the presence of HSA or fatted HSA. For slow-exchange (or strong) interactions, NMR resonance integrals report the free metabolite concentration, while for fast exchange (weak binding) the chemical shift reports on the binding. Hence, these metabolites bind strongly to HSA and/or fatted HSA, but to a limited degree because for most metabolites their concentration is smaller than the HSA concentration. Most interestingly, fatty acids decrease the HSA-metabolite binding quite significantly for most of the interacting metabolites. We further find that competition between the metabolites for binding is absent for most of these metabolites. These mappings in plasma mimics may thus open new opportunities for improved metabolic profiling of blood plasma. For instance, correct metabolite concentrations can be determined for the non-interacting metabolites and/or concentration corrections made for interacting metabolites. Secondly, the interacting metabolites could be used to act as reporters on HSA and fatty acid concentration in plasma, and thus potentially act as biomarker in diagnostic studies of trauma or cardiovascular diseases. Finally, we find in the blood plasma mimics that after ultrafiltration, commonly used to remove the protein from plasma, the measured concentration equals the total metabolite concentration, except for the strongest binding metabolite citrate.
Graphical abstract

Highlights

? Interaction with HSA of 20 common blood plasma metabolites is investigated by NMR. ? Most of these metabolites bind to HSA, but are released by fatty acids. ? Competition for HSA binding is absent for most of these metabolites. ? Protein removal by ultrafiltration does not remove metabolite, citrate excepted. ? These mappings provide leads to improved NMR metabolic profiling of blood plasma.





Source: Journal of Magnetic Resonance
Reply With Quote


Did you find this post helpful? Yes | No

Reply
Similar Threads
Thread Thread Starter Forum Replies Last Post
(1)H NMR study of monocrotaline and its metabolites in human blood.
(1)H NMR study of monocrotaline and its metabolites in human blood. (1)H NMR study of monocrotaline and its metabolites in human blood. Food Chem Toxicol. 2011 Aug 6; Authors: Yang YC, Crowder J, Wardle NJ, Yang L, White KN, Wang ZT, Annie Bligh SW Monocrotaline (MCT) is a naturally occurring hepatotoxic pyrrolizidine alkaloid found in plants. This investigation is aimed at furthering the understanding of the role of blood in mediating the transport of MCT and its reactive metabolites in humans. Reactions of monocrotaline and its metabolites,...
nmrlearner Journal club 0 08-17-2011 01:33 PM
DEER in Biological Multispin-Systems: A Case Study on the Fatty Acid Binding to Human Serum Albumin
DEER in Biological Multispin-Systems: A Case Study on the Fatty Acid Binding to Human Serum Albumin Publication year: 2011 Source: Journal of Magnetic Resonance, In Press, Accepted Manuscript, Available online 10 March 2011</br> Matthias J.N., Junk , Hans W., Spiess , Dariush, Hinderberger</br> In this study, self-assembled systems of human serum albumin (HSA) and spin-labeled fatty acids are characterized by double electron–electron resonance (DEER). HSA, being the most important transport protein of the human blood, is capable to host up to seven paramagnetic fatty acid...
nmrlearner Journal club 0 03-11-2011 05:00 PM
[NMR paper] Interaction of chicken liver basic fatty acid-binding protein with fatty acids: a 13C
Interaction of chicken liver basic fatty acid-binding protein with fatty acids: a 13C NMR and fluorescence study. Related Articles Interaction of chicken liver basic fatty acid-binding protein with fatty acids: a 13C NMR and fluorescence study. Biochemistry. 2001 Oct 23;40(42):12604-11 Authors: Beringhelli T, Goldoni L, Capaldi S, Bossi A, Perduca M, Monaco HL Two different groups of liver fatty acid-binding proteins (L-FABPs) are known: the mammalian type and the basic type. Very few members of this second group of L-FABPs have been...
nmrlearner Journal club 0 11-19-2010 08:44 PM
[NMR paper] The binding of 5-fluorouracil to native and modified human serum albumin: UV, CD, and
The binding of 5-fluorouracil to native and modified human serum albumin: UV, CD, and 1H and 19F NMR investigation. http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles The binding of 5-fluorouracil to native and modified human serum albumin: UV, CD, and 1H and 19F NMR investigation. J Pharm Biomed Anal. 1995 Aug;13(9):1087-93 Authors: Bertucci C, Ascoli G, Uccello-Barretta G, Di Bari L, Salvadori P 5-Fluorouracil (FU) is an important and widely used antineoplastic drug...
nmrlearner Journal club 0 08-22-2010 03:50 AM
[NMR paper] 13C NMR studies of the binding of medium-chain fatty acids to human serum albumin.
13C NMR studies of the binding of medium-chain fatty acids to human serum albumin. Related Articles 13C NMR studies of the binding of medium-chain fatty acids to human serum albumin. J Lipid Res. 1994 Mar;35(3):458-67 Authors: Kenyon MA, Hamilton JA Binding of the medium-chain fatty acids (MCFA), octanoic (OCT) and decanoic (DEC) acid, to human serum albumin (HSA) has been studied by 13C NMR spectroscopy. NMR spectra at 35 degrees C showed an apparently homogeneous binding environment (a single, narrow resonance for the 13C-enriched carboxyl...
nmrlearner Journal club 0 08-22-2010 03:33 AM
[NMR paper] 13C NMR studies of the binding of medium-chain fatty acids to human serum albumin.
13C NMR studies of the binding of medium-chain fatty acids to human serum albumin. Related Articles 13C NMR studies of the binding of medium-chain fatty acids to human serum albumin. J Lipid Res. 1994 Mar;35(3):458-67 Authors: Kenyon MA, Hamilton JA Binding of the medium-chain fatty acids (MCFA), octanoic (OCT) and decanoic (DEC) acid, to human serum albumin (HSA) has been studied by 13C NMR spectroscopy. NMR spectra at 35 degrees C showed an apparently homogeneous binding environment (a single, narrow resonance for the 13C-enriched carboxyl...
nmrlearner Journal club 0 08-22-2010 03:33 AM
[NMR paper] The influence of hydration on the conformation of bovine serum albumin studied by sol
The influence of hydration on the conformation of bovine serum albumin studied by solid-state 13C-NMR spectroscopy. Related Articles The influence of hydration on the conformation of bovine serum albumin studied by solid-state 13C-NMR spectroscopy. Biopolymers. 1993 Dec;33(12):1871-6 Authors: Gregory RB, Gangoda M, Gilpin RK, Su W 13C proton-decoupled cross-polarization magic-angle spinning nmr spectra of bovine serum albumin are reported as a function of hydration. Increases in hydration level enhance the resolution of the peak centered at...
nmrlearner Journal club 0 08-22-2010 03:01 AM
[NMR paper] 1H NMR studies of reactions of copper complexes with human blood plasma and urine.
1H NMR studies of reactions of copper complexes with human blood plasma and urine. Related Articles 1H NMR studies of reactions of copper complexes with human blood plasma and urine. Biochem Pharmacol. 1992 Jan 22;43(2):137-45 Authors: Bligh SW, Boyle HA, McEwen AB, Sadler PJ, Woodham RH Reactions of the copper complexes Cu(II)Cl2, 2-, and + (where DIPS is 3,5-diisopropylsalicylate and DMP is 2,9-dimethylphenanthroline) with human blood plasma and urine have been studied by 500 MHz 1H NMR spectroscopy, and CD spectroscopy has been used to...
nmrlearner Journal club 0 08-21-2010 11:41 PM



Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

BB code is On
Smilies are On
[IMG] code is On
HTML code is On
Trackbacks are Off
Pingbacks are Off
Refbacks are Off



BioNMR advertisements to pay for website hosting and domain registration. Nobody does it for us.



Powered by vBulletin® Version 3.7.3
Copyright ©2000 - 2024, Jelsoft Enterprises Ltd.
Copyright, BioNMR.com, 2003-2013
Search Engine Friendly URLs by vBSEO 3.6.0

All times are GMT. The time now is 10:59 PM.


Map