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Phase II Reactions: Acetylation Reactions01:24

Phase II Reactions: Acetylation Reactions

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Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
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Kendall's tau test, also known as the Kendall rank coefficient test, is a nonparametric method for assessing association between two variables. This test is particularly useful for identifying significant correlations when the distributions of the sample and population are unknown. Developed in 1938 by the British statistician Sir Maurice George Kendall, the tau coefficient (denoted as τ) serves as a rank correlation coefficient, with values ranging from -1 to +1.
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A phase diagram combines plots of pressure versus temperature for the liquid-gas, solid-liquid, and solid-gas phase-transition equilibria of a substance. These diagrams indicate the physical states that exist under specific conditions of pressure and temperature and also provide the pressure dependence of the phase-transition temperatures (melting points, sublimation points, boiling points). Regions or areas labeled solid, liquid, and gas represent single phases, while lines or curves represent...
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Whether solid, liquid, or gas, a substance's state depends on the order and arrangement of its particles (atoms, molecules, or ions). Particles in the solid pack closely together, generally in a pattern. The particles vibrate about their fixed positions but do not move or squeeze past their neighbors. In liquids, although the particles are closely spaced, they are randomly arranged. The position of the particles are not fixed—that is, they are free to move past their neighbors to...
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Understanding the inductance of transmission lines is crucial for efficient design and operation in electrical power systems. This discussion delves into the inductance characteristics of single-phase two-wire and three-phase three-wire transmission lines with equal phase spacing.
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Acetylation Disfavors Tau Phase Separation.

Josephine C Ferreon1, Antrix Jain2, Kyoung-Jae Choi3

  • 1Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA. josephine.ferreon@bcm.edu.

International Journal of Molecular Sciences
|May 9, 2018
PubMed
Summary
This summary is machine-generated.

Tau acetylation by p300 HAT disfavors liquid-liquid phase separation (LLPS) and aggregation, potentially preventing toxic effects but inhibiting microtubule assembly, contributing to Tau loss-of-function.

Keywords:
Tau fibrillationintrinsically disordered proteinmembrane-less organelleneurodegenerative diseasep300 HAT acetylationpost-translational modificationprotein aggregation

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Cell Biology

Background:

  • Microtubule-associated protein Tau aggregates are hallmarks of Alzheimer's disease.
  • Tau's liquid-liquid phase separation (LLPS) may initiate aggregation, similar to FUS and TDP-43.
  • The impact of Tau hyperacetylation on LLPS and aggregation is largely unknown.

Purpose of the Study:

  • To investigate the effect of Tau acetylation on its phase separation and aggregation propensity.
  • To determine if Tau acetylation influences LLPS-initiated aggregation and microtubule assembly.

Main Methods:

  • Investigated Tau acetylation using p300 histone acetyltransferase (HAT).
  • Assessed Tau's liquid-liquid phase separation (LLPS) potential.
  • Monitored heparin-induced Tau aggregation.
  • Examined the effect on LLPS-initiated microtubule assembly.

Main Results:

  • Hyperacetylation of Tau by p300 HAT disfavors LLPS.
  • Acetylation inhibits heparin-induced Tau aggregation.
  • Tau acetylation impedes LLPS-initiated microtubule assembly.

Conclusions:

  • Tau acetylation prevents toxic LLPS-dependent aggregation.
  • Acetylation contributes to Tau loss-of-function by inhibiting microtubule assembly.
  • Acetylation represents a regulatory mechanism for Tau's phase separation and aggregation.