scholarly journals Dissociation from the Oligomeric State Is the Rate-limiting Step in Fibril Formation by κ-Casein

2008 ◽  
Vol 283 (14) ◽  
pp. 9012-9022 ◽  
Author(s):  
Heath Ecroyd ◽  
Tomas Koudelka ◽  
David C. Thorn ◽  
Danielle M. Williams ◽  
Glyn Devlin ◽  
...  
Keyword(s):  
Fibril Formation ◽  
Oligomeric State ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting

scholarly journals Mechanistic insights into the protective roles of polyphosphate against amyloid cytotoxicity

2019 ◽  
Vol 2 (5) ◽  
pp. e201900486 ◽  
Author(s):  
Justine Lempart ◽  
Eric Tse ◽  
James A Lauer ◽  
Magdalena I Ivanova ◽  
Alexandra Sutter ◽  
...  
Keyword(s):  
Extracellular Space ◽  
Therapeutic Strategy ◽  
Neuronal Cells ◽  
Lewy Bodies ◽  
Fibril Formation ◽  
Amyloid Protein ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Fibril Morphology ◽  
Rate Limiting

The universally abundant polyphosphate (polyP) accelerates fibril formation of disease-related amyloids and protects against amyloid cytotoxicity. To gain insights into the mechanism(s) by which polyP exerts these effects, we focused on α-synuclein, a well-studied amyloid protein, which constitutes the major component of Lewy bodies found in Parkinson’s disease. Here, we demonstrate that polyP is unable to accelerate the rate-limiting step of α-synuclein fibril formation but effectively nucleates fibril assembly once α-synuclein oligomers are formed. Binding of polyP to α-synuclein either during fibril formation or upon fibril maturation substantially alters fibril morphology and effectively reduces the ability of α-synuclein fibrils to interact with cell membranes. The effect of polyP appears to be α-synuclein fibril specific and successfully prevents the uptake of fibrils into neuronal cells. These results suggest that altering the polyP levels in the extracellular space might be a potential therapeutic strategy to prevent the spreading of the disease.

scholarly journals Mechanistic Insights into the Protective Roles of Polyphosphate Against Amyloid Cytotoxicity

2019 ◽  
Author(s):  
Justine Lempart ◽  
Eric Tse ◽  
James A. Lauer ◽  
Magdalena I Ivanova ◽  
Alexandra Sutter ◽  
...  
Keyword(s):  
Extracellular Space ◽  
Therapeutic Strategy ◽  
Neuronal Cells ◽  
Lewy Bodies ◽  
Fibril Formation ◽  
Amyloid Protein ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Fibril Morphology ◽  
Rate Limiting

ABSTRACTThe universally abundant polyphosphate (polyP) accelerates fibril formation of disease-related amyloids and protects against amyloid cytotoxicity. To gain insights into the mechanism(s) by which polyP exerts these effects, we focused on α-synuclein, a well-studied amyloid protein, which constitutes the major component of Lewy bodies found in Parkinson’s Disease. Here we demonstrate that polyP is unable to accelerate the rate-limiting step of α-synuclein fibril formation but effectively nucleates fibril assembly once α-synuclein oligomers are formed. Binding of polyP to α-synuclein either during fibril formation or upon fibril maturation substantially alters fibril morphology, and effectively reduces the ability of α-synuclein fibrils to interact with cell membranes. The effect of polyP appears to be α-synuclein fibril specific, and successfully prevents the uptake of fibrils into neuronal cells. These results suggest that altering the polyP levels in the extracellular space might be a potential therapeutic strategy to prevent the spreading of the disease.

Ornithine Decarboxylase Activity in Cultured Endothelial Cells Stimulated by Serum, Thrombin and Serotonin

1978 ◽  
Vol 39 (02) ◽  
pp. 496-503 ◽  
Author(s):  
P A D’Amore ◽  
H B Hechtman ◽  
D Shepro
Keyword(s):  
Endothelial Cells ◽  
Ornithine Decarboxylase ◽  
Decarboxylase Activity ◽  
Aortic Endothelial Cells ◽  
Ornithine Decarboxylase Activity ◽  
Rate Limiting Step ◽  
Bovine Aortic Endothelial Cells ◽  
Limiting Step ◽  
Rate Limiting ◽  
Serum Serotonin

SummaryOrnithine decarboxylase (ODC) activity, the rate-limiting step in the synthesis of polyamines, can be demonstrated in cultured, bovine, aortic endothelial cells (EC). Serum, serotonin and thrombin produce a rise in ODC activity. The serotonin-induced ODC activity is significantly blocked by imipramine (10-5 M) or Lilly 11 0140 (10-6M). Preincubation of EC with these blockers together almost completely depresses the 5-HT-stimulated ODC activity. These observations suggest a manner by which platelets may maintain EC structural and metabolic soundness.

Dynamics of hepatic and peripheral insulin effects suggest common rate-limiting step in vivo

Diabetes ◽  
1993 ◽  
Vol 42 (2) ◽  
pp. 296-306 ◽  
Author(s):  
D. C. Bradley ◽  
R. A. Poulin ◽  
R. N. Bergman
Keyword(s):  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting

Kinetics of cyclization of S-ethoxycarbonylmethylisothiouronium chloride to 2-imino-4-thiazolidone

1979 ◽  
Vol 44 (3) ◽  
pp. 912-917 ◽  
Author(s):  
Vladimír Macháček ◽  
Said A. El-bahai ◽  
Vojeslav Štěrba
Keyword(s):  
Hydrochloric Acid ◽  
Dilute Hydrochloric Acid ◽  
Base Catalysis ◽  
General Base ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Kinetics Of Formation ◽  
Acid Catalyzed ◽  
Rate Limiting ◽  
Kinetics Of

Kinetics of formation of 2-imino-4-thiazolidone from S-ethoxycarbonylmethylisothiouronium chloride has been studied in aqueous buffers and dilute hydrochloric acid. The reaction is subject to general base catalysis, the β value being 0.65. Its rate limiting step consists in acid-catalyzed splitting off of ethoxide ion from dipolar tetrahedral intermediate. At pH < 2 formation of this intermediate becomes rate-limiting; rate constant of its formation is 2 . 104 s-1.

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