本質的に反応性のあるプライマリグリコリート代謝産物による機能性ライシン変異
Raymond E Moellering1, Benjamin F Cravatt
1The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA. rmoeller@scripps.edu
Science (New York, N.Y.)
|August 3, 2013
まとめ
メタボリットは,翻訳後の改変によってタンパク質の機能を調節する. 1,3-ビスホスホグリセラート (1,3-BPG) はタンパク質を非酵素的に変異させ,3-フォスホスホスホグリセリルライシン (pgK) を形成し,糖分解を調節する.
科学分野:
- バイオケミストリー バイオケミストリー
- メタボロミクスとは
- プロテオミクス プロテオミクスは,プロテオミクスの
背景:
- タンパク質の翻訳後の改変は,生物学的調節に極めて重要です.
- メタボリートとタンパク質の相互作用は,細胞代謝とタンパク質の機能の間の直接的なリンクを提供します.
研究 の 目的:
- タンパク質の非酵素的変異を,グリコリチス中介物質によって調査する.
- 関連する特定の代謝産物と,その結果生じるタンパク質の改変を特定する.
- この改変が細胞代謝に及ぼす機能的影響を調査する.
主な方法:
- プロテオミックプロファイリングにより,変異したタンパク質とサイトを特定します.
- 1,3-BPGとライシン残基の反応を特徴付けるための生化学的分析.
- 酵素活性アッセイは,変化がグリコリチス酵素に与える影響を評価するためのものです.
主要な成果:
- 1,3-bisphosphoglycerate (1,3-BPG) を反応性代謝物として特定した.
- タンパク質,特に糖分解酵素に3フォスフォグリセリルライシン (pgK) 変異の形成を発見した.
- pgKの改変が酵素活性を抑制し,高血糖状態で蓄積することを実証した.
結論:
- 1,3-BPGはタンパク質を直接改変し,糖分解のフィードバックループを作成します.
- pgKの改変は,代謝の流れに影響を与える規制メカニズムとして機能します.
- この発見は,細胞経路における代謝媒介タンパク質調節の新しい層を明らかにしています.
さらに関連する動画
関連する概念動画
00:56What is Glycolysis?
Overview
Cells make energy by breaking down macromolecules. Cellular respiration is the biochemical process that converts "food energy" (from the chemical bonds of macromolecules) into chemical energy in the form of adenosine triphosphate (ATP). The first step of this tightly regulated and intricate process is glycolysis. The word glycolysis originates from the Latin glyco (sugar) and lysis (breakdown). Glycolysis serves two main intracellular functions: generating ATP and generating...
Cells make energy by breaking down macromolecules. Cellular respiration is the biochemical process that converts "food energy" (from the chemical bonds of macromolecules) into chemical energy in the form of adenosine triphosphate (ATP). The first step of this tightly regulated and intricate process is glycolysis. The word glycolysis originates from the Latin glyco (sugar) and lysis (breakdown). Glycolysis serves two main intracellular functions: generating ATP and generating...
01:23Glycolysis
Glycolysis, the Embden-Meyerhof pathway, is a central metabolic pathway involved in glucose catabolism. It is highly conserved across most organisms, reflecting its fundamental role in cellular energy production. This process occurs in the cytoplasm and can function both in the presence and absence of oxygen, making it versatile for various organisms and environmental conditions.Stages of GlycolysisGlycolysis is a ten-step pathway that converts glucose into pyruvate, generating a net gain of...
01:20Fates of Pyruvate
Pyruvate is the end product of glycolysis, where glucose is oxidized to pyruvate, simultaneously reducing NAD+ to NADH. Two molecules of ATP are also produced by substrate-level phosphorylation.
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...
01:24Other Glycolytic Pathways
The pentose phosphate pathway (PPP) operates in parallel with glycolysis, facilitating the metabolism of both pentoses and glucose. This pathway consists of two distinct phases: the oxidative and non-oxidative phases. While it does not directly generate ATP, the intermediates formed during the process can integrate into glycolysis, contributing to cellular energy metabolism when required.Oxidative Phase: NADPH ProductionThe oxidative phase of the pentose phosphate pathway is primarily...
01:15Pyruvate Oxidation
After glycolysis, the charged pyruvate molecules enter the mitochondria via active transport and undergo three enzymatic reactions. These reactions ensure that pyruvate can enter the next metabolic pathway so that energy stored in the pyruvate molecules can be harnessed by the cells.
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
01:22Lysosomal Hydrolases
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...