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Carbohydrate Digestion00:57

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Carbohydrate digestion and metabolism break down simple and complex carbohydrates from food into saccharides (i.e., sugars) for the body to use as energy. Carbohydrate digestion starts in the mouth during mastication, or chewing. The masticated carbohydrates remain intact in the stomach. Digestion resumes in the duodenum of the small intestine, where pancreatic alpha-amylase and brush border enzymes of the microvilli convert complex carbohydrates to monosaccharides. Finally, the monosaccharides...
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α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
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Carbohydrates are polymers composed of molecules containing atoms of carbon, hydrogen and oxygen. One gram of carbohydrate can provide four kilo-calories of energy, which makes it the most efficient instant energy source.
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Polysaccharides such as glycogen and starch are synthesized from nucleoside diphosphate sugars, primarily uridine diphosphate glucose (UDPG) and adenosine diphosphate glucose (ADPG). These activated glucose donors act as key intermediates in carbohydrate metabolism and biosynthesis. UDPG primarily involves glycogen synthesis in animals and many bacteria, while ADPG plays a fundamental role in starch synthesis in plants and certain bacteria.UDPG is formed when glucose-1-phosphate reacts with...
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Carbohydrates, proteins, and fats are the primary macronutrients in the human diet. However, carbohydrates are the most favored source of energy in the body. They can be found in a wide variety of foods, including whole grains, fruit, and vegetables, in various forms, such as sugars, starch, and dietary fiber. Based on their structure, carbohydrates are classified into three main classes— monosaccharides, disaccharides, and polysaccharides. The body's cells can only utilize simple...
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酵素活性化糖でコーティングされた二機能分解剤

Qian Zhu1, Gerhard Fischer2, Steven S Cheng1

  • 1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States.

Journal of the American Chemical Society
|September 12, 2025
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まとめ

研究者は,標的型タンパク質の分解のために糖分の一部を酵素で除去する必要のある糖分を対象とした糖分分解キメラ (SCP) を開発した. この代謝ゲート戦略は,O-GlcNAc変異とO-GlcNAcase (OGA) 酵素による活動制御により,PROTACの選択性を高めます.

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科学分野:

  • 生物化学
  • 分子生物学
  • 化学生物学

背景:

  • 標的型タンパク質分解は,タンパク質をユビキチン-プロテアゾーム系に誘導するプロテオリシス標的型キメラ (PROTAC) を利用する.
  • 一般的に使用されるセレブロン (CRBN) のようなE3リガゼは広範囲に発現し,PROTACの選択性を制限する.
  • 治療特異性を高めるには,PROTACの代謝ゲート化のための戦略の開発が不可欠です.

研究 の 目的:

  • O-GlcNAc改変を用いたPROTACsのための新しい酵素活性化戦略を開発する.
  • O-GlcNAcの酵素除去によって活性化される砂糖で覆われたPROTAC (SCP) を生成する.
  • O-GlcNAcの改変がCRBN結合と標的タンパク質の分解に与える影響を調査する.

主な方法:

  • CRBNとBRD4を複合したサイクルミドの構造分析
  • O-GlcNAc改変サイクリミッド (SCP) の合成
  • In vitro生化学結合測定法,細胞分解測定法,細胞活性の測定法

主要な成果:

  • サイクリミドのグリコシライゼーションにより,CRBN結合とBRD4との複合体の形成が低下した.
  • O-GlcNAcをO-GlcNAcase (OGA) による酵素による除去により,CRBN結合が回復し,標的タンパク質の分解が誘発された.
  • エンジニアリングとネイティブの細胞系での酵素活性化のための実証された要求.

結論:

  • O-GlcNAcの改変は,標的タンパク質の分解を代謝的にゲートする効果的なメカニズムとして機能する.
  • 酵素活性化戦略は,PROTACの選択性を高めることができます.
  • このアプローチは,選択性の向上のために他のタンパク質の改変を用いた類似の戦略の開発を促します.