在教学中通过脱羧线索解析三羧酸循环

Teaching of tricarboxylic acid cycle via decarboxylation clues

摘要:

三羧酸循环的反应过程复杂，中间产物多样、知识点密集，是生物化学课程教学中的重点和难点。在现有教学中，教师们通常按照三羧酸循环的反应步骤依次讲解(简称顺序法)，但其教与学的效果尚具有提升的空间。为了简化反应过程和产物术语的复杂度，使学生易于理解和掌握三羧酸循环的反应途径和作用机制，同时提升教学质量，本文提出了一种教学思路，即通过脱羧反应的线索来解析三羧酸循环(脱羧解析法)。首先，脱羧解析法展示了丙酮酸脱羧形成的乙酰辅酶A与草酰乙酸反应，形成的柠檬酸分子中的2-羧甲基在三羧酸循环的第一轮循环未参与脱羧。然后，采用R代表羧甲基对三羧酸循环进行分析发现，从乙酰辅酶A与草酰乙酸缩合开始，三羧酸循环的部分中间产物化学式可以对应写成：柠檬酸(R-2-苹果酸)、顺乌头酸(R-延胡索酸)、异柠檬酸(R-3-苹果酸)、α-酮戊二酸(R-丙酮酸)、琥珀酰辅酶A (R-乙酰辅酶A)、琥珀酸(R-乙酸)。三羧酸循环的两次脱羧分别发生在异柠檬酸和α-酮戊二酸。为了检验“脱羧解析法”的教学效果，本文招募学生开展接受“脱羧解析法”教学前后学习效果的问卷调查，并对反馈结果进行统计分析显示，接受脱羧解析法教学后，绝大多数学生都感觉“三羧酸循环”的每一步反应变得容易理解和记忆了。“脱羧解析”教学法对学习效果的提升有助于启发学生的思考与分析，促进学生的学习能动性与创新精神，从而获得更好的学习效果。

Abstract:

The tricarboxylic acid (TCA) cycle is a crucial yet challenging topic in the teaching of Biochemistry due to its complex reactions and dense knowledge points. Conventional teaching method typically follows the sequence of the reactions in the TCA cycle, which often resulting in suboptimal learning outcomes. This paper introduces an alternative teaching method with introduction of decarboxylation clues to simplify the reaction process and product terminology in the TCA cycle, making it easier for students to understand the pathways and mechanisms involved. Firstly, the dissection of decarboxylation demonstrates that pyruvate undergoes decarboxylation to form acetyl-CoA, which reacts with oxaloacetate to produce the 2-carboxymethyl group in citrate. This 2-carboxymethyl group does not participate in decarboxylation during the first round of the TCA cycle. Subsequently, with R representing carboxymethyl for analyzing the TCA cycle, it is found that starting from the condensation of acetyl-CoA and oxaloacetate, the chemical formulas of some intermediates in the TCA cycle can be correspondingly written as follows: citrate (R-2-malate), cis-aconitate (R-fumarate), isocitrate (R-3-malate), α-ketoglutarate (R-pyruvate), succinyl-CoA (R-acetyl-CoA), and succinate (R-acetate). The two decarboxylation steps in the TCA cycle occur in isocitrate and α-ketoglutarate, respectively. To evaluate the effectiveness of this new teaching method, we recruited students to participate in a survey assessing their learning outcomes before and after teaching with this method. Statistical analysis of the feedback results showed that the majority of students taught with this new method found each step of the TCA cycle easier to understand and remember, with significant improvement in learning outcomes. The teaching method with decarboxylation clues enhances learning outcomes by stimulating students’ thinking and analysis and promoting their learning initiative and innovative spirit, thereby leading to better learning results.