Metzger Robert P
Department of Chemistry and Biochemistry, San Diego State University, San Diego, California 92182-1030.
Biochem Mol Biol Educ. 2006 Mar;34(2):78-87. doi: 10.1002/bmb.2006.49403402078.
Systems biology, metabolomics, metabolic engineering, and other recent developments in biochemistry suggest that future biochemists will require a detailed familiarity with the compounds and pathways of intermediary metabolism and their biochemical control. The challenge to the biochemistry instructor is the presentation of metabolic pathways in a manner that allows student creativity in learning the pathways and their components. One approach that does permit the use of problem solving for the study of metabolic pathways involves following the fate of (13) C, (14) C, or (15) N labels, presented originally in the structure of an important metabolic starting compound, through relevant metabolic pathways. This method allows the presentation and study of problems in which such an isotopic label can be traced through two or more metabolic pathways, thus illustrating how these pathways are interconnected. The understanding that all the pathways of intermediary metabolism are interconnected provides opportunities to discuss their metabolic control by such mechanisms as signaling, feedback inhibition, location in organelles, coenzyme levels, and coenzyme recycling rates. The method is illustrated by following the fate of (14) C labels through anaerobic glycolysis, gluconeogenesis, and fatty acid transport, β-oxidation, and ketone body formation. Cholesterol biosynthesis and heme formation are used to show that presentations of long and complex pathways can demonstrate important biochemical concepts by following the fate of an isotopic label using only the most important intermediates. Problems based on tracing radioactive labels through one or more metabolic pathways allow the use of cooperative learning techniques.
系统生物学、代谢组学、代谢工程以及生物化学领域的其他最新进展表明,未来的生物化学家需要详细熟悉中间代谢的化合物和途径及其生化调控。生物化学教师面临的挑战是以一种能让学生在学习这些途径及其组成部分时发挥创造力的方式来呈现代谢途径。一种确实允许通过解决问题来研究代谢途径的方法是追踪最初存在于一种重要代谢起始化合物结构中的碳 - 13、碳 - 14 或氮 - 15 标记,使其通过相关代谢途径。这种方法能够呈现和研究这样的问题:其中这种同位素标记可以通过两条或更多代谢途径被追踪,从而说明这些途径是如何相互连接的。认识到所有中间代谢途径都是相互连接的,就提供了机会来讨论通过诸如信号传导、反馈抑制、在细胞器中的定位、辅酶水平以及辅酶循环速率等机制对它们进行的代谢调控。通过追踪碳 - 14 标记在无氧糖酵解、糖异生以及脂肪酸转运、β - 氧化和酮体形成过程中的去向来说明该方法。胆固醇生物合成和血红素形成用于表明,通过仅使用最重要的中间体追踪同位素标记的去向,对于长而复杂途径的呈现可以阐明重要的生化概念。基于通过一条或多条代谢途径追踪放射性标记的问题允许使用合作学习技术。