ATGLは,ヒドロキシ脂肪酸の脂肪酸エステルの生合成酵素である

Rucha Patel¹, Anna Santoro¹, Peter Hofer²

¹Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Nature

|June 8, 2022

まとめ

アディポストリグリセリドリパゼ (ATGL) は,ヒドロキシ脂肪酸 (FAHFA) の脂肪酸エステルを合成する最初の酵素である. この発見はATGLを明らかにします.

科学分野:

脂質生化学
酵素学
代謝疾患の研究

背景:

ハイドロキシ脂肪酸の脂肪酸エステル (FAHFA) は哺乳類で発見された新しい脂質である.
ハイドロキシステアリック酸 (PAHSA) のサブファミリーであるパルミチン酸エステルは,抗炎症および抗糖尿病特性を有する.
PAHSA濃度の低下は,ヒトとマウスのインスリン抵抗性に関連しています.

研究の目的:

FAHFAのバイオシンセシスに関与する酵素を in vivoで特定する.
特定された酵素によって触媒化されたFAHFA形成のメカニズムを解明する.

主な方法:

化学生物学とプロテオミクスは,候補酵素を特定するために使用された.
触媒機能を確認するために,再結合酵素活性アッセイが行われました.
マウスと細胞モデルでの遺伝子ノックアウトと過剰発現の研究が利用された.

主要な成果:

アディポストリグリセリドリパース (ATGL) はFAHFAの生物合成における重要な酵素として特定されました.
ATGLは,トリグリセリド (TG) またはディグリセリドを用いたトランザサイレーション反応を通じてFAHFA形成を触媒化する.
ATGLの遺伝的消去または化学的抑制により,内生的なFAHFAとFAHFA- TGのレベルが著しく低下した.

結論:

ATGLは,FAHFA合成に不可欠な,以前に認識されていないトランサイラゼ活性を持っています.
この発見により,ATGLはFAHFAエステル結合形成を触媒する哺乳類の酵素として初めて確認された.
ATGLのトランサチラゼ活性には,代謝および炎症性疾患に対する潜在的な臨床的関連性があります.

さらに関連する動画

06:52

Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile

Published on: October 30, 2018

36.4K

20:28

A Toolkit to Enable Hydrocarbon Conversion in Aqueous Environments

Published on: October 2, 2012

14.2K

関連する概念動画

01:07

Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis

3.6K

Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an...

3.6K

01:28

Overview of Fatty Acid Metabolism

31.8K

Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...

31.8K

01:13

Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Mechanism

8.2K

Carboxylic acids react with alcohols to yield esters via an acid-catalyzed condensation reaction called Fischer esterification. This is a nucleophilic acyl substitution reaction that proceeds via a tetrahedral intermediate, where a water molecule is eliminated as the leaving group.

8.2K

01:20

Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Overview

18.6K

The Fischer esterification reaction was developed by the German chemist Emil Fischer in 1895. It is a condensation reaction between carboxylic acids and alcohols in an acidic medium to give esters and water.

18.6K

01:13

Esters to Carboxylic Acids: Acid-Catalyzed Hydrolysis

3.2K

Hydrolysis of esters under acidic conditions proceeds through a nucleophilic acyl substitution. In the presence of excess water, the reaction proceeds in a reversible manner, forming carboxylic acids and alcohols.
During hydrolysis, the ester is first activated towards nucleophilic attack through the protonation of the carboxyl oxygen atom by the acid catalyst. The protonation makes the ester carbonyl carbon more electrophilic. In the next step, water acts as a nucleophile and adds to the...

3.2K

01:08

Esters to β-Ketoesters: Claisen Condensation Mechanism

3.8K

Regular Claisen condensation involves the synthesis of β-ketoesters by combining identical ester molecules bearing two α hydrogens in the presence of an alkoxide base. The reaction commences with the deprotonation of the acidic α hydrogen by the base to form a resonance stabilized ester enolate. This nucleophilic ion then attacks the carbonyl center of another ester molecule to generate a tetrahedral alkoxide intermediate. Next, the expulsion of the alkoxide group from the...