scholarly journals Renal metabolism of amino acids: its role in interorgan amino acid exchange

2004 ◽  
Vol 79 (2) ◽  
pp. 185-197 ◽  
Author(s):  
Marcel CG van de Poll ◽  
Peter B Soeters ◽  
Nicolaas EP Deutz ◽  
Kenneth CH Fearon ◽  
Cornelis HC Dejong
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Exchange ◽  
Renal Metabolism ◽  
Acid Exchange

Influence of hyperinsulinaemia on intracellular amino acid levels and amino acid exchange across splanchnic and leg tissues in uraemia

1988 ◽  
Vol 74 (2) ◽  
pp. 155-163 ◽  
Author(s):  
Anders Alvestrand ◽  
Ralph A. Defronzo ◽  
Douglas Smith ◽  
John Wahren
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Concentrations ◽  
Amino Acid Exchange ◽  
Control Subjects ◽  
Intracellular Amino Acid ◽  
Resistance To Insulin ◽  
And Control ◽  
Amino Acid Concentrations ◽  
Acid Exchange

1. To examine whether insulin resistance in uraemia extends to amino acid metabolism, the effect of physiological hyperinsulinaemia on plasma amino acid concentrations was studied in 17 chronically uraemic and 28 healthy subjects by using the euglycaemic insulin clamp technique. 2. In six uraemic and seven control subjects, splanchnic and leg exchange of amino acids was quantified with hepatic and femoral venous catheterization, and in five uraemic and eight control subjects intracellular free amino acid concentrations were determined in muscle tissue obtained by needle biopsy. 3. In response to hyperinsulinaemia the plasma concentrations of all amino acids except alanine decreased by 10–50% in both uraemic and control subjects. Splanchnic alanine uptake declined by 20% and leg amino acid release tended to decrease in both groups. 4. The intracellular levels of all measured amino acids except alanine fell significantly and to a similar extent in uraemic and control subjects. 5. These results indicate that insulin-mediated alterations in regional amino acid exchange and in plasma and intracellular amino acid concentrations are similar in uraemic and control subjects. 6. It is concluded that tissue insensitivity to insulin in uraemia does not extend to uptake or release of amino acids and that resistance to insulin can be selective in its effect on different metabolic functions.

Increased plasma plant sterol concentrations and a heterozygous amino acid exchange in ATP binding cassette transporter ABCG5: A case report

2011 ◽  
Vol 54 (4) ◽  
pp. e458-e460 ◽  
Author(s):  
Sylvia Keller ◽  
Danielle Prechtl ◽  
Charalampos Aslanidis ◽  
Uta Ceglarek ◽  
Joachim Thiery ◽  
...  
Keyword(s):  
Case Report ◽  
Amino Acid ◽  
Plant Sterol ◽  
Atp Binding ◽  
Amino Acid Exchange ◽  
Atp Binding Cassette Transporter ◽  
Acid Exchange ◽  
Plasma Plant ◽  
Atp Binding Cassette

scholarly journals Collapse of the native structure caused by a single amino acid exchange in human NAD (P)H:quinone oxidoreductase 1

FEBS Journal ◽  
2014 ◽  
Vol 281 (20) ◽  
pp. 4691-4704 ◽  
Author(s):  
Wolf‐Dieter Lienhart ◽  
Venugopal Gudipati ◽  
Michael K. Uhl ◽  
Alexandra Binter ◽  
Sergio A. Pulido ◽  
...  
Keyword(s):  
Amino Acid ◽  
Single Amino Acid ◽  
Native Structure ◽  
Amino Acid Exchange ◽  
Acid Exchange

Apical and basolateral 4F2hc and the amino acid exchange of L-DOPA in renal LLC-PK1 cells

Amino Acids ◽  
2005 ◽  
Vol 29 (3) ◽  
pp. 213-219 ◽  
Author(s):  
P. Soares-da-Silva ◽  
M. P. Serrão
Keyword(s):  
Amino Acid ◽  
Amino Acid Exchange ◽  
Acid Exchange

scholarly journals Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms

2015 ◽  
Vol 29 (6) ◽  
pp. 2583-2594 ◽  
Author(s):  
Kate L. Widdows ◽  
Nuttanont Panitchob ◽  
Ian P. Crocker ◽  
Colin P. Please ◽  
Mark A. Hanson ◽  
...  
Keyword(s):  
Amino Acid ◽  
Computational Modeling ◽  
Membrane Transport ◽  
Transport Mechanisms ◽  
Amino Acid Exchange ◽  
Transport Studies ◽  
Acid Exchange

scholarly journals Impact of Capsid Conformation and Rep-Capsid Interactions on Adeno-Associated Virus Type 2 Genome Packaging

2006 ◽  
Vol 80 (2) ◽  
pp. 810-820 ◽  
Author(s):  
Svenja Bleker ◽  
Michael Pawlita ◽  
Jürgen A. Kleinschmidt
Keyword(s):  
Amino Acid ◽  
Capsid Protein ◽  
Amino Acid Exchange ◽  
Genome Packaging ◽  
Adeno Associated Virus ◽  
Rep Proteins ◽  
Axes Of Symmetry ◽  
Conserved Amino Acids ◽  
Acid Exchange

ABSTRACT Single-stranded genomes of adeno-associated virus (AAV) are packaged into preformed capsids. It has been proposed that packaging is initiated by interaction of genome-bound Rep proteins to the capsid, thereby targeting the genome to the portal of encapsidation. Here we describe a panel of mutants with amino acid exchanges in the pores at the fivefold axes of symmetry on AAV2 capsids with reduced packaging and reduced Rep-capsid interaction. Mutation of two threonines at the rim of the fivefold pore nearly completely abolished Rep-capsid interaction and packaging. This suggests a Rep-binding site at the highly conserved amino acids at or close to the pores formed by the capsid protein pentamers. A different mutant (P. Wu, W. Xiao, T. Conlon, J. Hughes, M. Agbandje-McKenna, T. Ferkol, T. Flotte, and N. Muzyczka, J. Virol. 74:8635-8647, 2000) with an amino acid exchange at the interface of capsid protein pentamers led to a complete block of DNA encapsidation. Analysis of the capsid conformation of this mutant revealed that the pores at the fivefold axes were occupied by VP1/VP2 N termini, thereby preventing DNA introduction into the capsid. Nevertheless, the corresponding capsids had more Rep proteins bound than wild-type AAV, showing that correct Rep interaction with the capsid depends on a defined capsid conformation. Both mutant types together support the conclusion that the pores at the fivefold symmetry axes are involved in genome packaging and that capsid conformation-dependent Rep-capsid interactions play an essential role in the packaging process.

The pattern of amino acid exchange across the brain is unaffected by intravenous glutamine supplementation in head trauma patients

2008 ◽  
Vol 27 (6) ◽  
pp. 816-821 ◽  
Author(s):  
Agneta Berg ◽  
Bo Michael Bellander ◽  
Michael Wanecek ◽  
Åke Norberg ◽  
Urban Ungerstedt ◽  
...  
Keyword(s):  
Amino Acid ◽  
Head Trauma ◽  
Glutamine Supplementation ◽  
Trauma Patients ◽  
Amino Acid Exchange ◽  
The Brain ◽  
Acid Exchange

Emergence of canine distemper in Bavarian wildlife associated with a specific amino acid exchange in the haemagglutinin protein

2011 ◽  
Vol 187 (3) ◽  
pp. 399-401 ◽  
Author(s):  
Karin Sekulin ◽  
Angela Hafner-Marx ◽  
Jolanta Kolodziejek ◽  
Dirk Janik ◽  
Peter Schmidt ◽  
...  
Keyword(s):  
Amino Acid ◽  
Canine Distemper ◽  
Amino Acid Exchange ◽  
Specific Amino Acid ◽  
Acid Exchange

A Novel Fusion Gene NDEL1-Pdgfrb in a Patient with JMML with a New Variant of TKI-Resistant Mutation in the Kinase Domain of PDGFRβ

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 613-613 ◽  
Author(s):  
Konstantin Byrgazov ◽  
Renate Kastner ◽  
Michael Dworzak ◽  
Gregor Hoermann ◽  
Oskar A. Haas ◽  
...  
Keyword(s):  
Amino Acid ◽  
Tyrosine Kinase ◽  
Fusion Gene ◽  
Kinase Domain ◽  
Juvenile Myelomonocytic Leukemia ◽  
Fusion Partner ◽  
Amino Acid Exchange ◽  
Inactive Conformation ◽  
Clinical Resistance ◽  
Acid Exchange

Abstract We have identified a novel fusion gene in an 18-month old child with juvenile myelomonocytic leukemia (JMML) displaying a reciprocal chromosomal translocation t(5;7)(q33;p11.2). Molecular investigation at diagnosis revealed absence of mutations in KRAS, NRAS, PTPN11, or cCBL, but FISH analysis identified a rearrangement involving the PDGFRB gene located on chromosome 5q33. After temporary responses to imatinib (IM) and subsequently nilotinib (NIL) treatment, resistance associated with disease relapses was observed. Employment of the 5’-RACE technique facilitated identification of the PDGFRB fusion partner on chromosome 7p11.2, the NDEL1 gene encoding the nudE neurodevelopmental protein 1-like 1. The NDEL1 gene has not been implicated in any other reciprocal translocation to date, and it is conceivable that its ability to form dimers could drive permanent kinase activation of PDGFRβ. The chimeric mRNA contains the 5´exons 1-5 of NDEL1 fused in frame to the PDGFRB exons 10-22 containing the transmembrane and tyrosine kinase domains. To assess the oncogenicity of the fusion protein, Ba/F3 cells were transduced with the NDEL1-PDGFRB gene construct. The observation of IL3-independent growth confirmed the oncogenic potential of the novel fusion gene. The observed clinical resistance to IM and NIL prompted us to analyze the entire PDGFRB kinase domain for the presence of mutations by Sanger sequencing of overlapping amplicons. A point mutation in the activation (A) loop converting aspartate at the position 850 into glutamate (D850E) was detected in peripheral blood specimens from the time of first and second relapses, but not in the diagnostic sample. The crystal structure of the PDGFRβ TKD is not available, but protein modelling suggested that the mutation D850E destabilizes the inactive confirmation of the A-loop. This notion was in line with the observed clinical resistance to IM and NIL, but suggested sensitivity of the mutant to dasatinib (DAS). To test the predicted TKI responses, Ba/F3 cells transduced with wild type or mutant NDEL1-PDGFRB were tested in MTT assays against a panel of TKIs: Ba/F3-NDEL1-PDGFRBWT cells were sensitive to IM (IC50 = 60 nM), NIL (100 nM), DAS (5 nM), sorafenib (SOR; 20 nM), and ponatinib (PON; 10 nM), but insensitive to bosutinib (BOS; >2500 nM). Conversely, Ba/F3-NDEL1-PDGFRBD850E cells exhibited high resistance to IM (>2500), a 10-fold higher IC50 for NIL (1000 nM) and a 100-fold higher IC50 for SOR (2500 nM), but retained sensitivity to PON (15 nM) and DAS (15 nM). Mutations in the A-loop of different tyrosine kinases such as PDGFRα (D842V) or c-Kit (D816V) associated with resistance to IM have already been described in different tumor entities. However, the mutation D850E in the PDGFRβ TKD with apparent insensitivity to IM, NIL, and SOR revealed a completely different pattern of resistance than the same amino acid exchange at the corresponding site of PDGFRα (D842E). The latter mutation was previously shown to be sensitive to IM, NIL, and SOR with IC50 values of 4, 12.5, and 0.25 nM, respectively. This difference is intriguing because the exchange of a negatively charged amino acid, aspartate, to an amino acid with the same physical properties, glutamate, is not known to exert a major structural effect on the protein conformation, as observed for the D842E mutation in PDGFRα. We speculate that the great difference between the presence of the same amino acid exchange at corresponding positions in PDGFRα and PDGFRβ is the main interaction amino acid partner residue of aspartate at the position +3 which may influence the stability of the A-loop in its inactive conformation. In PDGFRα, it is histidine whose physical interaction with aspartate might not be affected by the change to glutamate. By contrast, the electrostatic bonds between arginine as the +3 residue in PDGFRβ might be greatly weakened by the elongation of the side chain in glutamate in comparison with aspartate, thus destabilizing the inactive conformation of the A-loop resulting in resistance to type II TKIs. To our knowledge, this is the first observation of an exchange between two negatively charged amino acids in a tyrosine kinase associated with a major change in responsiveness to TKI treatment. This finding is currently under further investigation, and may extend our understanding of structural interactions leading to TKI resistance. (Supported by the FWF SFB grant F4705-B20). Disclosures Valent: Novartis: Consultancy, Honoraria, Research Funding.

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